32 results on '"Lia S. Campos"'
Search Results
2. Offspring of mothers with bipolar disorder: a systematic review considering personality features
- Author
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Rodrigo A. Bastos, Lia S. Campos, Débora B. Faria-Schützer, Maíra E. Brito, Diego R. da Silva, Amilton dos Santos-Junior, and Egberto R. Turato
- Subjects
Bipolar disorder ,adult children ,mother-child relations ,caregivers ,systematic review ,Psychiatry ,RC435-571 - Abstract
Objective: To examine personality/temperament features and mental health vulnerability in offspring of mothers with bipolar disorders (BD), including dimensions which may impact psychological characteristics or therapeutic measures. Methods: A systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, was conducted to search for original articles that investigated personality/temperament features of offspring of women with BD and emotional factors involved in the mother-child relationship. The electronic search was performed in the PubMed, Web of Science, and PsycINFO databases from February 2010 to February 2017. Results: Ten quantitative studies were included in the analysis: seven from the United States, two from Brazil, and one from Canada. The narrative synthesis was categorized into three dimensions: 1) reliability of instruments for prediction of future psychopathology in offspring; 2) environmental risk factors for offspring; and 3) early interventions. The findings showed impairments in the offspring’s lives, high rates of behavior and temperament problems, and psychiatric disorders. Conclusion: BD is a frequent psychiatric disorder, and the offspring of mothers with this condition are exposed to complex family relationships and psychosocial difficulties. If they are to ensure a good provision of mental health and psychosocial care to this unique population, early interventions must not neglect their contextual specificities. Systematic review registration: PROSPERO CRD-42017039010
- Published
- 2021
- Full Text
- View/download PDF
3. BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma
- Author
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Kyren A. Lazarus, Fazal Hadi, Elisabetta Zambon, Karsten Bach, Maria-Francesca Santolla, Julie K. Watson, Lucia L. Correia, Madhumita Das, Rosemary Ugur, Sara Pensa, Lukas Becker, Lia S. Campos, Graham Ladds, Pentao Liu, Gerard I. Evan, Frank M. McCaughan, John Le Quesne, Joo-Hyeon Lee, Dinis Calado, and Walid T. Khaled
- Subjects
Science - Abstract
Amongst the non-small cell lung cancers, to date, lung squamous cell carcinoma remains the most challenging to treat. Here the authors report BCL11A as an important factor which together with SOX2 can drive lung squamous cell carcinoma development and highlight a potential novel therapeutic candidate for this devastating disease.
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- 2018
- Full Text
- View/download PDF
4. Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway.
- Author
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Yong Yu, Jason C. H. Tsang, Cui Wang, Simon Clare, Juexuan Wang, Xi Chen 0039, Cordelia Brandt, Leanne Kane, Lia S. Campos, Liming Lu, Gabrielle T. Belz, Andrew N. J. McKenzie, Sarah A. Teichmann, Gordon Dougan, and Pentao Liu
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- 2016
- Full Text
- View/download PDF
5. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
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Elena Prigmore, Louis-François Handfield, Michael R. Stratton, Tong Li, Mercedes Jimenez-Linan, Lucy Gardner, Luz Garcia-Alonso, Tarryn Porter, Krishnaa T. Mahbubani, Vitalii Kleshchevnikov, Anna Arutyunyan, Hassan Massalha, Monika Dabrowska, Paul Ayuk, Kwasi Kwakwa, Ashley Moffett, Benjamin Woodhams, Kourosh Saeb-Parsy, Ridma C. Fernando, Regina Hoo, Elizabeth Tuck, Konstantina Nikolakopoulou, Stijn van Dongen, Valentina Lorenzi, Jong-Eun Park, Kenny Roberts, Cecilia Icoresi Mazzeo, Margherita Y. Turco, Vasyl Vaskivskyi, Martin Prete, Aleksandra Tarkowska, Roser Vento-Tormo, Krzysztof Polanski, Carmen Sancho-Serra, Cecilia Lindskog, Omer Ali Bayraktar, Vladimir Yu. Kiselev, Sarah A. Teichmann, Lia S. Campos, Luiza Moore, Roberts, Kenny [0000-0001-6155-0821], Nikolakopoulou, Konstantina [0000-0003-2306-590X], Woodhams, Benjamin [0000-0003-2801-5733], Arutyunyan, Anna [0000-0003-0453-5443], Polanski, Krzysztof [0000-0002-2586-9576], Li, Tong [0000-0002-8240-4476], Vaskivskyi, Vasyl [0000-0002-4080-4965], Mahbubani, Krishnaa T. [0000-0002-1327-2334], Stratton, Michael R. [0000-0001-6035-153X], Saeb-Parsy, Kourosh [0000-0002-0633-3696], Moffett, Ashley [0000-0002-8388-9073], Moore, Luiza [0000-0001-5315-516X], Bayraktar, Omer A. [0000-0001-6055-277X], Teichmann, Sarah A. [0000-0002-6294-6366], Vento-Tormo, Roser [0000-0002-9870-8474], Apollo - University of Cambridge Repository, Mahbubani, Krishnaa T [0000-0002-1327-2334], Stratton, Michael R [0000-0001-6035-153X], Bayraktar, Omer A [0000-0001-6055-277X], Teichmann, Sarah A [0000-0002-6294-6366], Mahbubani, Krishnaa [0000-0002-1327-2334], and Teichmann, Sarah [0000-0002-6294-6366]
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631/45 ,Cell type ,Notch signaling pathway ,Reproduktionsmedicin och gynekologi ,In Vitro Techniques ,Cell fate determination ,Biology ,Endometrium ,Tissue Culture Techniques ,Transcriptome ,Spatio-Temporal Analysis ,Downregulation and upregulation ,Obstetrics, Gynecology and Reproductive Medicine ,Genetics ,Organoid ,medicine ,Humans ,Cell Lineage ,Gonadal Steroid Hormones ,Menstrual Cycle ,Receptors, Notch ,Uterus ,article ,Wnt signaling pathway ,Cell Differentiation ,Endometrial Neoplasms ,Cell biology ,Organoids ,Wnt Proteins ,medicine.anatomical_structure ,Cellular Microenvironment ,Female ,631/80 ,Signal Transduction - Abstract
The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma. Single-cell and spatial transcriptomic profiling of the human endometrium highlights pathways governing the proliferative and secretory phases of the menstrual cycle. Analyses of endometrial organoids show that WNT and NOTCH signaling modulate differentiation into the secretory and ciliated epithelial lineages, respectively. Correction in: Nature Genetics, 55, page 165 (2023)DOI: 10.1038/s41588-022-01287-6
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- 2021
6. Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence
- Author
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S M Ashiqul Islam, Irina I. Abnizova, James McKay, Yudou He, Estelle Chanudet, Behnoush Abedi-Ardekani, Dariush Nasrollahzadeh, Michael Eden, Alisa M. Goldstein, Jon W. Teague, Blandina T. Mmbaga, Nan Hu, Karl Smith-Byrne, Sandra Perdomo, Jingwei Wang, Christine Carreira, Jean-Yves Scoazec, Rebecca C. Fitzgerald, Luis Felipe Ribeiro, Michael R. Stratton, Samad Gharavi, Sergey Senkin, Erik N Bergstrom, Hiva Saffar, Sarah Moody, Sheila Coelho Soares-Lima, Pauline E Bucciarelli, Stefano Serra, Ghislaine Scelo, Charles Dzamalala, Valerie McCormack, Reza Malekzadeh, Hossein Poustchi, Valerie Gaborieau, Lia S Campos, Joshua R. Atkins, Paul Brennan, Emily Thomas, David T. Jones, Paul Richman, Farid Azmoudeh-Ardalan, Masoud Sotoudeh, Ahmadreza Niavarani, Tatsuhiro Shibata, Calli Latimer, Stephen Fitzgerald, Ludmil B Alexandrov, Ricardo Cortez Cardoso Penha, Abdolreza Fazel, Laura Humphreys, Azhar Khandekar, Arash Nikmanesh, and Diana Menya
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Adult ,Male ,APOBEC ,China ,Esophageal Neoplasms ,Apolipoprotein B ,Iran ,Biology ,medicine.disease_cause ,Genome ,Esophageal squamous cell carcinoma ,Germline ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology of cancer ,Genetics ,medicine ,Humans ,APOBEC Deaminases ,Aged ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,Mutation ,Whole Genome Sequencing ,Aldehyde Dehydrogenase, Mitochondrial ,Incidence ,Incidence (epidemiology) ,Middle Aged ,United Kingdom ,digestive system diseases ,3. Good health ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Female ,Esophageal Squamous Cell Carcinoma ,Tumor Suppressor Protein p53 ,Brazil - Abstract
Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.
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- 2021
7. Cells of the human intestinal tract mapped across space and time
- Author
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Cecilia Domínguez Conde, Ni Huang, Omer Ali Bayraktar, Krishnaa T. Mahbubani, Holm H. Uhlig, Justin Engelbert, Steven Leonard, Emma Dann, Minal Patel, Aaron M. Fleming, Sara F. Vieira, C. Elizabeth Hook, Sarah A. Teichmann, Lia S. Campos, Emily Stephenson, Issac Goh Kai’En, Sophie Pritchard, Stijn van Dongen, Michael D Morgan, Kourosh Saeb-Parsy, Krzysztof Polanski, Rasa Elmentaite, Kenny Roberts, John C. Marioni, Thomas R. W. Oliver, Natsuhiko Kumasaka, Matthias Zilbauer, Roger A. Barker, Francesca Perrone, Kylie R. James, Kerstin B Meyer, Muzlifah Haniffa, Komal Nayak, Menna R. Clatworthy, Vitalii Kleshchevnikov, Steven Lisgo, Liam Bolt, Lira Mamanova, Xiaoling He, Monika Dabrowska, Rachel A. Botting, Matilda Katan, Hamish W King, Elmentaite, Rasa [0000-0001-7366-5466], Kumasaka, Natsuhiko [0000-0002-3557-0375], Roberts, Kenny [0000-0001-6155-0821], Dann, Emma [0000-0002-7400-7438], King, Hamish W. [0000-0001-5972-8926], Bolt, Liam [0000-0001-7293-0774], Vieira, Sara F. [0000-0002-1021-3021], Mamanova, Lira [0000-0003-1463-8622], Katan, Matilda [0000-0001-9992-8375], Oliver, Thomas R. W. [0000-0003-4306-0102], Domínguez Conde, Cecilia [0000-0002-8684-4655], Botting, Rachel A. [0000-0001-9595-4605], Polanski, Krzysztof [0000-0002-2586-9576], Morgan, Michael D. [0000-0003-0757-0711], Marioni, John C. [0000-0001-9092-0852], Bayraktar, Omer Ali [0000-0001-6055-277X], Meyer, Kerstin B. [0000-0001-5906-1498], Uhlig, Holm H. [0000-0002-6111-7355], Mahbubani, Krishnaa T. [0000-0002-1327-2334], Saeb-Parsy, Kourosh [0000-0002-0633-3696], Zilbauer, Matthias [0000-0002-7272-0547], Haniffa, Muzlifah [0000-0002-3927-2084], James, Kylie R. [0000-0002-7107-0650], Teichmann, Sarah A. [0000-0002-6294-6366], Apollo - University of Cambridge Repository, King, Hamish W [0000-0001-5972-8926], Vieira, Sara F [0000-0002-1021-3021], Oliver, Thomas RW [0000-0003-4306-0102], Botting, Rachel A [0000-0001-9595-4605], Morgan, Michael D [0000-0003-0757-0711], Marioni, John C [0000-0001-9092-0852], Meyer, Kerstin B [0000-0001-5906-1498], Uhlig, Holm H [0000-0002-6111-7355], Mahbubani, Krishnaa T [0000-0002-1327-2334], James, Kylie R [0000-0002-7107-0650], Teichmann, Sarah A [0000-0002-6294-6366], and Oliver, Thomas R W [0000-0003-4306-0102]
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Aging ,Time Factors ,Organogenesis ,Cell ,Datasets as Topic ,Inflammatory bowel disease ,14 ,Enteric Nervous System ,Mice ,Crohn Disease ,Child ,631/114/2391 ,health care economics and organizations ,Crohn's disease ,Multidisciplinary ,article ,humanities ,Cell biology ,Intestines ,medicine.anatomical_structure ,Health ,Female ,38/39 ,medicine.symptom ,631/136 ,Signal Transduction ,Adult ,Cellular signalling networks ,education ,Inflammation ,Biology ,38/91 ,14/32 ,Immune system ,Fetus ,Spatio-Temporal Analysis ,692/699/1503/257/1402 ,Developmental biology ,medicine ,Animals ,Humans ,45 ,Receptors, IgG ,Epithelial Cells ,medicine.disease ,Embryonic stem cell ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Metagenome ,Enteric nervous system ,Lymph Nodes - Abstract
Funder: Medical Research Council, The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.
- Published
- 2021
- Full Text
- View/download PDF
8. Mutational signatures in esophageal squamous cell carcinoma from eight countries of varying incidence
- Author
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Jean-Yves Scoazec, S M Ashiqul Islam, Irina I. Abnizova, Diana Menya, Paul Richman, Dariush Nasrollahzadeh, Michael R. Stratton, Charles Dzamalala, Sergey Senkin, Karl Smith-Byrne, Hiva Saffar, Pauline E Bucciarelli, Christine Carreira, Sarah Moody, Michael Eden, Paul Brennan, Yudou He, Lia S Campos, Azhar Khandekar, Erik N. Bergstrom, Arash Nikmanesh, Abdolreza Fazel, Ghislaine Scelo, Valerie Gaborieau, Farid Azmoudeh-Ardelan, Calli Latimer, Ricardo Cortez Cardoso Penha, Laura Humphreys, Stefano Serra, Jon W. Teague, Tatsuhiro Shibata, Ludmil B. Alexandrov, Estelle Chanudet, Masoud Sotoudeh, Jingwei Wang, Blandina T. Mmbaga, Valerie McCormack, Reza Malekzadeh, Rebecca C. Fitzgerald, Joshua R. Atkins, David T. Jones, Sandra Perdomo, Emily Thomas, Luis Felipe Ribeiro, Alisa M. Goldstein, Stephen Fitzgerald, Behnoush Abedi-Ardekani, James McKay, and Nan Hu
- Subjects
APOBEC ,Mutation ,Environmental risk ,Incidence (epidemiology) ,Epidemiology of cancer ,medicine ,Cancer research ,Biology ,medicine.disease_cause ,neoplasms ,Esophageal squamous cell carcinoma ,digestive system diseases ,Germline - Abstract
Esophageal squamous cell carcinoma (ESCC) shows a remarkable variation in incidence which is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. The mutational profiles of ESCC were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining the differences in ESCC incidence. APOBEC associated mutational signatures SBS2 and SBS13 were present in 88% and 91% of cases respectively and accounted for a quarter of the mutation burden on average, indicating that activation of APOBEC is a crucial step in ESCC tumor development.
- Published
- 2021
9. Cells of the human intestinal tract mapped across space and time
- Author
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Sarah A. Teichmann, Lia S. Campos, Emma Dann, Sophie Pritchard, K Saeb Parsy, Ni Huang, Justin Engelbert, Sara F. Vieira, Krishnaa T. Mahbubani, Steve Lisgo, Matthias Zilbauer, Minal Patel, Holm H. Uhlig, Morgan, Aaron M. Fleming, Matilda Katan, Hamish W King, Omer Ali Bayraktar, C Dominguez-Conde, Natsuhiko Kumasaka, Clatworthy, Krzysztof Polanski, Francesca Perrone, Rasa Elmentaite, Emily Stephenson, Steven Leonard, S. van Dongen, Kerstin B. Meyer, Komal Nayak, I Goh Kai’En, Kylie R. James, Muzlifah Haniffa, CE Hook, John C. Marioni, Monika Dabrowska, Liam Bolt, Lira Mamanova, Rachel A. Botting, Trw Oliver, and Kenny Roberts
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Cell type ,Cell ,Inflammation ,Biology ,medicine.disease ,Inflammatory bowel disease ,Cell biology ,Pathogenesis ,medicine.anatomical_structure ,Immune system ,medicine ,Enteric nervous system ,medicine.symptom ,Homeostasis - Abstract
The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. To comprehensively map cell lineages in the healthy developing, pediatric and adult human gut from ten distinct anatomical regions, as well as draining lymph nodes, we used singlecell RNA-seq and VDJ analysis of roughly one third of a million cells. This reveals the presence of BEST4+ absorptive cells throughout the human intestinal tract, demonstrating the existence of this cell type beyond the colon for the first time. Furthermore, we implicate IgG sensing as a novel function of intestinal tuft cells, and link these cells to the pathogenesis of inflammatory bowel disease. We define novel glial and neuronal cell populations in the developing enteric nervous system, and predict cell-type specific expression of Hirschsprung’s disease-associated genes. Finally, using a systems approach, we identify key cell players across multiple cell lineages driving secondary lymphoid tissue formation in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. These data provide an unprecedented catalogue of intestinal cells, and new insights into cellular programs in development, homeostasis and disease.
- Published
- 2021
10. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
- Author
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Luz Garcia-Alonso, Ridma C. Fernando, Regina Hoo, Kenny Roberts, Vasyl Vaskivskyi, Vitalii Kleshchevnikov, Aleksandra Tarkowska, Anna Arutyunyan, Jong-Eun Park, Roser Vento-Tormo, Cecilia Icoresi Mazzeo, Tong Li, Tarryn Porter, Kourosh Saeb-Parsy, Paul Ayuk, Michael R. Stratton, Monika Dabrowska, Ashley Moffett, Louis-François Handfield, Elena Prigmore, Ben Woodhams, Stijn van Dongen, Elizabeth Tuck, Krishna T. Mahbubani, Mercedes Jimenez-Linan, Lucy Gardner, Konstantina Nikolakopoulou, Kwasi Kwakwa, Margherita Y. Turco, Krzysztof Polanski, Omer Ali Bayraktar, Vladimir Yu. Kiselev, Carmen Sancho-Serra, Cecilia Lindskog, Sarah A. Teichmann, Lia S. Campos, and Luiza Moore
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medicine.anatomical_structure ,Downregulation and upregulation ,In vivo ,Wnt signaling pathway ,medicine ,Uterus ,Organoid ,Endometriosis ,Cell fate determination ,Biology ,Endometrium ,medicine.disease ,Cell biology - Abstract
The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures. We dissect the signalling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids highlights common pathways regulating the differentiation of secretory and ciliated lineage in vivo and in vitro. We show in vitro that downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. These mechanistic insights provide a platform for future development of treatments for a range of common endometrial disorders including endometriosis and carcinoma.
- Published
- 2021
11. Offspring of mothers with bipolar disorder: a systematic review considering personality features
- Author
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Amilton dos Santos-Júnior, Rodrigo Almeida Bastos, Diego Alexandre Rozendo da Silva, Egberto Ribeiro Turato, Lia S. Campos, Débora Bicudo Faria-Schützer, and Maíra Esteves Brito
- Subjects
caregivers ,Bipolar Disorder ,Offspring ,Bipolar disorder ,media_common.quotation_subject ,Population ,Psychological intervention ,RC435-571 ,Mothers ,Personality Disorders ,systematic review ,Personality ,Humans ,adult children ,education ,Temperament ,mother-child relations ,media_common ,Psychiatry ,education.field_of_study ,Reproducibility of Results ,Mental health ,Psychiatry and Mental health ,Systematic review ,Female ,Psychology ,Psychosocial ,Clinical psychology - Abstract
Objective: To examine personality/temperament features and mental health vulnerability in offspring of mothers with bipolar disorders (BD), including dimensions which may impact psychological characteristics or therapeutic measures. Methods: A systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, was conducted to search for original articles that investigated personality/temperament features of offspring of women with BD and emotional factors involved in the mother-child relationship. The electronic search was performed in the PubMed, Web of Science, and PsycINFO databases from February 2010 to February 2017. Results: Ten quantitative studies were included in the analysis: seven from the United States, two from Brazil, and one from Canada. The narrative synthesis was categorized into three dimensions: 1) reliability of instruments for prediction of future psychopathology in offspring; 2) environmental risk factors for offspring; and 3) early interventions. The findings showed impairments in the offspring’s lives, high rates of behavior and temperament problems, and psychiatric disorders. Conclusion: BD is a frequent psychiatric disorder, and the offspring of mothers with this condition are exposed to complex family relationships and psychosocial difficulties. If they are to ensure a good provision of mental health and psychosocial care to this unique population, early interventions must not neglect their contextual specificities. Systematic review registration: PROSPERO CRD-42017039010
- Published
- 2020
12. Tumors induce de novo steroid biosynthesis in T cells to evade immunity
- Author
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Klaus Okkenhaug, Edward Ryder, Izabela Walczak, Sarah A. Teichmann, Lia S. Campos, Jacqueline D. Shields, Nuno A. Fonseca, Bidesh Mahata, Angela Riedel, David J. Adams, Xi Chen, Jhuma Pramanik, Krzysztof Polanski, Gozde Kar, Louise van der Weyden, Kousik Kundu, Graham Duddy, Mahata, Bidesh [0000-0002-4506-0184], Polanski, Krzysztof [0000-0002-2586-9576], Chen, Xi [0000-0003-2648-3146], Fonseca, Nuno A [0000-0003-4832-578X], Kundu, Kousik [0000-0002-1019-8351], Ryder, Edward [0000-0002-1799-9899], Okkenhaug, Klaus [0000-0002-9432-4051], Adams, David J [0000-0001-9490-0306], Shields, Jacqueline D [0000-0003-2153-9710], Teichmann, Sarah A [0000-0002-6294-6366], Apollo - University of Cambridge Repository, Fonseca, Nuno A. [0000-0003-4832-578X], Adams, David J. [0000-0001-9490-0306], Shields, Jacqueline D. [0000-0003-2153-9710], and Teichmann, Sarah A. [0000-0002-6294-6366]
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0301 basic medicine ,CD4-Positive T-Lymphocytes ,medicine.medical_treatment ,animal diseases ,Druggability ,General Physics and Astronomy ,Transcriptome ,13/1 ,Mice ,0302 clinical medicine ,lcsh:Science ,Melanoma ,Mice, Knockout ,0303 health sciences ,Multidisciplinary ,article ,Immunosuppression ,Primary tumor ,3. Good health ,Cell biology ,13/31 ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,9 ,38/77 ,Tumour immunology ,64/60 ,Steroids ,631/67/327 ,Cancer microenvironment ,Science ,Transgene ,T cell ,13/106 ,chemical and pharmacologic phenomena ,Steroid biosynthesis ,Biology ,General Biochemistry, Genetics and Molecular Biology ,38 ,38/91 ,03 medical and health sciences ,Immune system ,13/21 ,Immunity ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cholesterol Side-Chain Cleavage Enzyme ,030304 developmental biology ,Immune Evasion ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,030104 developmental biology ,Cell culture ,631/67/580 ,Cancer cell ,Cancer research ,bacteria ,lcsh:Q - Abstract
Tumors subvert immune cell function to evade immune responses, yet the complex mechanisms driving immune evasion remain poorly understood. Here we show that tumors induce de novo steroidogenesis in T lymphocytes to evade anti-tumor immunity. Using a transgenic steroidogenesis-reporter mouse line we identify and characterize de novo steroidogenic immune cells, defining the global gene expression identity of these steroid-producing immune cells and gene regulatory networks by using single-cell transcriptomics. Genetic ablation of T cell steroidogenesis restricts primary tumor growth and metastatic dissemination in mouse models. Steroidogenic T cells dysregulate anti-tumor immunity, and inhibition of the steroidogenesis pathway is sufficient to restore anti-tumor immunity. This study demonstrates T cell de novo steroidogenesis as a mechanism of anti-tumor immunosuppression and a potential druggable target., Multiple mechanisms of immune evasion exploited by cancer cells have been described. Here, the authors show that genetic inactivation or pharmacological inhibition of tumor-induced Th2-mediated de novo steroidogenesis are sufficient to restore an efficient anti-tumor immune response and restrict tumor growth.
- Published
- 2020
13. MiR-25 regulates Wwp2 and Fbxw7 and promotes reprogramming of mouse fibroblast cells to iPSCs.
- Author
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Dong Lu, Matthew P A Davis, Cei Abreu-Goodger, Wei Wang, Lia S Campos, Julia Siede, Elena Vigorito, William C Skarnes, Ian Dunham, Anton J Enright, and Pentao Liu
- Subjects
Medicine ,Science - Abstract
miRNAs are a class of small non-coding RNAs that regulate gene expression and have critical functions in various biological processes. Hundreds of miRNAs have been identified in mammalian genomes but only a small number of them have been functionally characterized. Recent studies also demonstrate that some miRNAs have important roles in reprogramming somatic cells to induced pluripotent stem cells (iPSCs).We screened 52 miRNAs cloned in a piggybac (PB) vector for their roles in reprogramming of mouse embryonic fibroblast cells to iPSCs. To identify targets of miRNAs, we made Dgcr8-deficient embryonic stem (ES) cells and introduced miRNA mimics to these cells, which lack miRNA biogenesis. The direct target genes of miRNA were identified through global gene expression analysis and target validation.We found that over-expressing miR-25 or introducing miR-25 mimics enhanced production of iPSCs. We identified a number of miR-25 candidate gene targets. Of particular interest were two ubiquitin ligases, Wwp2 and Fbxw7, which have been proposed to regulate Oct4, c-Myc and Klf5, respectively. Our findings thus highlight the complex interplay between miRNAs and transcription factors involved in reprogramming, stem cell self-renewal and maintenance of pluripotency.
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- 2012
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- View/download PDF
14. Establishment of porcine and human expanded potential stem cells
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Liangxue Lai, Song-Guo Xue, Wolf Reik, Beiyuan Fu, Heiner Niemann, Dongsheng Chen, Asif Ahmed, Xi Chen, Monika Nowak-Imialek, Peng Li, Pentao Liu, Patrick P.L. Tam, Yi Zhang, Guocheng Lan, Duanqing Pei, Doris Herrmann, Sarah A. Teichmann, Xiangang Zou, Lia S. Campos, Donghai Wu, Fengtang Yang, Liu Zuohua, Jian Wu, Tao Nie, William S.B. Yeung, Andy Chun Hang Chen, Jixing Zhong, Xuefei Gao, Shengpeng Wang, Liming Lu, Jiacheng Zhu, Mélanie A. Eckersley-Maslin, Zhouchun Shang, Liliana Antunes, Susan J. Kimber, David Ryan, Stoyan Petkov, Azim Surani, Toshihiro Kobayashi, Xiaomin Wang, Jian Yang, Degong Ruan, Shakil Ahmad, Ge Liangpeng, Yong Huang, Yin Lau Lee, Yu Yong, TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany., Chen, Xi [0000-0003-2648-3146], Kobayashi, Toshihiro [0000-0001-8019-0008], Lan, Guocheng [0000-0001-9063-5728], Li, Peng [0000-0003-4530-2400], Zhang, Yi [0000-0001-9861-4681], Yang, Fengtang [0000-0002-3573-2354], Shang, Zhouchun [0000-0002-1740-7961], Surani, Azim [0000-0002-8640-4318], Tam, Patrick PL [0000-0001-6950-8388], Teichmann, Sarah A [0000-0002-6294-6366], Niemann, Heiner [0000-0003-0282-9704], Liu, Pentao [0000-0001-5774-9678], and Apollo - University of Cambridge Repository
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Pluripotent Stem Cells ,Blastomeres ,Swine ,Somatic cell ,Cell Differentiation/genetics ,Induced Pluripotent Stem Cells ,Cell ,Germ layer ,Biology ,Cellular Reprogramming/genetics ,Regenerative Medicine ,Regenerative medicine ,Article ,Mice ,03 medical and health sciences ,Cell Lineage/genetics ,0302 clinical medicine ,Induced Pluripotent Stem Cells/cytology ,Germ Layers/growth & development ,medicine ,Animals ,Humans ,Cell Lineage ,Induced pluripotent stem cell ,Blastomeres/cytology ,Embryonic Stem Cells ,030304 developmental biology ,0303 health sciences ,Embryonic Stem Cells/cytology ,Stem Cells ,musculoskeletal, neural, and ocular physiology ,Trophoblast ,Cell Differentiation ,Pluripotent Stem Cells/cytology ,Cell Biology ,Cellular Reprogramming ,Embryonic stem cell ,Trophoblasts ,Cell biology ,medicine.anatomical_structure ,nervous system ,030220 oncology & carcinogenesis ,Signal Transduction/genetics ,Stem cell ,Totipotent Stem Cells ,Trophoblasts/cytology ,Germ Layers ,Signal Transduction - Abstract
We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.
- Published
- 2019
15. Expanded potential stem cell media as a tool to study human developmental hematopoiesis in vitro
- Author
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Berthold Göttgens, Pentao Liu, Beiyuan Fu, Adam C. Wilkinson, Lia S. Campos, Wei Wang, Evangelia Diamanti, Sonia Nestorowa, Fengtang Yang, David Ryan, Iwo Kucinski, Jason C.H. Tsang, Jian Yang, Juexuan Wang, Nicola K. Wilson, Kucinski, Iwo [0000-0002-9385-0359], Wilson, Nicola [0000-0003-0865-7333], Gottgens, Berthold [0000-0001-6302-5705], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Pluripotent Stem Cells ,Cancer Research ,Human Embryonic Stem Cells ,Cell Culture Techniques ,Embryoid body ,Biology ,Regenerative medicine ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neural Stem Cells ,Species Specificity ,Genes, Reporter ,Genetics ,Animals ,Humans ,Cell Lineage ,Cellular Reprogramming Techniques ,Induced pluripotent stem cell ,Molecular Biology ,Cells, Cultured ,Embryoid Bodies ,Sequence Analysis, RNA ,Cell Cycle ,Teratoma ,Gene targeting ,Cell Biology ,Hematology ,Fibroblasts ,3. Good health ,Cell biology ,Culture Media ,Hematopoiesis ,Transplantation ,Haematopoiesis ,030104 developmental biology ,030220 oncology & carcinogenesis ,Stem cell ,Stem Cell Transplantation - Abstract
Highlights • Expanded Potential Stem Cell Medium (EPSCM) stably maintains human pluripotent stem cells (PSCs). • EPSCM-maintained human PSCs can undergo hematopoietic differentiation in vitro. • A human SPI1-reporter PSC line enables study of in vitro hematopoiesis., Pluripotent stem cell (PSC) differentiation in vitro represents a powerful and tractable model to study mammalian development and an unlimited source of cells for regenerative medicine. Within hematology, in vitro PSC hematopoiesis affords novel insights into blood formation and represents an exciting potential approach to generate hematopoietic and immune cell types for transplantation and transfusion. Most studies to date have focused on in vitro hematopoiesis from mouse PSCs and human PSCs. However, differences in mouse and human PSC culture protocols have complicated the translation of discoveries between these systems. We recently developed a novel chemical media formulation, expanded potential stem cell medium (EPSCM), that maintains mouse PSCs in a unique cellular state and extraembryonic differentiation capacity. Herein, we describe how EPSCM can be directly used to stably maintain human PSCs. We further demonstrate that human PSCs maintained in EPSCM can spontaneously form embryoid bodies and undergo in vitro hematopoiesis using a simple differentiation protocol, similar to mouse PSC differentiation. EPSCM-maintained human PSCs generated at least two hematopoietic cell populations, which displayed distinct transcriptional profiles by RNA-sequencing (RNA-seq) analysis. EPSCM also supports gene targeting using homologous recombination, affording generation of an SPI1 (PU.1) reporter PSC line to study and track in vitro hematopoiesis. EPSCM therefore provides a useful tool not only to study pluripotency but also hematopoietic cell specification and developmental-lineage commitment.
- Published
- 2019
16. Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway
- Author
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Andrew N. J. McKenzie, Cordelia Brandt, Cui Wang, Gabrielle T. Belz, Leanne Kane, Sarah A. Teichmann, Yong Yu, Lia S. Campos, Xi Chen, Simon Clare, Pentao Liu, Juexuan Wang, Liming Lu, Gordon Dougan, and Jason C. H. Tsang
- Subjects
0301 basic medicine ,Multidisciplinary ,Cellular differentiation ,medicine.medical_treatment ,Innate lymphoid cell ,Biology ,Cell biology ,body regions ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Cytokine ,030220 oncology & carcinogenesis ,Immunology ,medicine ,Lymphopoiesis ,Progenitor cell ,skin and connective tissue diseases ,Tissue homeostasis ,Progenitor - Abstract
Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and they are important regulators of immune responses and tissue homeostasis. ILCs are generated from common lymphoid progenitors, which are subsequently committed to innate lymphoid lineages in the α-lymphoid progenitor, early innate lymphoid progenitor, common helper innate lymphoid progenitor and innate lymphoid cell progenitor compartments. ILCs consist of conventional natural killer cells and helper-like cells (ILC1, ILC2 and ILC3). Despite recent advances, the cellular heterogeneity, developmental trajectory and signalling dependence of ILC progenitors are not fully understood. Here, using single-cell RNA-sequencing (scRNA-seq) of mouse bone marrow progenitors, we reveal ILC precursor subsets, delineate distinct ILC development stages and pathways, and report that high expression of programmed death 1 (PD-1hi) marked a committed ILC progenitor that was essentially identical to an innate lymphoid cell progenitor. Our data defined PD-1hiIL-25Rhi as an early checkpoint in ILC2 development, which was abolished by deficiency in the zinc-finger protein Bcl11b but restored by IL-25R overexpression. Similar to T lymphocytes, PD-1 was upregulated on activated ILCs. Administration of a PD-1 antibody depleted PD-1hi ILCs and reduced cytokine levels in an influenza infection model in mice, and blocked papain-induced acute lung inflammation. These results provide a perspective for exploring PD-1 and its ligand (PD-L1) in immunotherapy, and allow effective manipulation of the immune system for disease prevention and therapy.
- Published
- 2016
17. Signalling Through Retinoic Acid Receptors is Required for Reprogramming of Both Mouse Embryonic Fibroblast Cells and Epiblast Stem Cells to Induced Pluripotent Stem Cells
- Author
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Lia S. Campos, Wei Wang, Pentao Liu, Liming Lu, Jian Yang, and Jolene Ooi
- Subjects
Receptors, Retinoic Acid ,Induced Pluripotent Stem Cells ,Tretinoin ,Embryoid body ,Biology ,Ligands ,Embryonic Stem Cells/Induced Pluripotent Stem Cells ,Kruppel-Like Factor 4 ,Mice ,Retinoic acid receptor gamma ,SOX2 ,Retinoic acid receptors ,Animals ,Liver receptor homolog‐1 ,Induced pluripotent stem cell ,Wnt Signaling Pathway ,beta Catenin ,Induced stem cells ,β‐Catenin ,Reprogramming ,Cell Biology ,Fibroblasts ,Cellular Reprogramming ,Embryo, Mammalian ,Embryonic stem cell ,Cell biology ,KLF4 ,embryonic structures ,Immunology ,Molecular Medicine ,Stem cell ,Germ Layers ,Epiblast stem cells ,Signal Transduction ,Transcription Factors ,Developmental Biology - Abstract
We previously demonstrated that coexpressing retinoic acid (RA) receptor gamma and liver receptor homolog-1 (LRH1 or NR5A2) with OCT4, MYC, KLF4, and SOX2 (4F) rapidly reprograms mouse embryonic fibroblast cells (MEFs) into induced pluripotent stem cells (iPSCs). Here, we further explore the role of RA in reprogramming and report that the six factors (6F) efficiently and directly reprogram MEFs into integration-free iPSCs in defined medium (N2B27) in the absence of feeder cells. Through genetic and chemical approaches, we find that RA signalling is essential, in a highly dose-sensitive manner, for MEF reprogramming. The removal of exogenous RA from N2B27, the inhibition of endogenous RA synthesis or the expression of a dominant-negative form of RARA severely impedes reprogramming. By contrast, supplementing N2B27 with various retinoids substantially boosts reprogramming. In addition, when coexpressed with LRH1, RA receptors (RARs) can promote reprogramming in the absence of both exogenous and endogenously synthesized RA. Remarkably, the reprogramming of epiblast stem cells into embryonic stem cell-like cells also requires low levels of RA, which can modulate Wnt signalling through physical interactions of RARs with β-catenin. These results highlight the important functions of RA signalling in reprogramming somatic cells and primed stem cells to naïve pluripotency. Stem Cells 2015;33:1390–1404
- Published
- 2015
18. Establishment of mouse expanded potential stem cells
- Author
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Hideki Masaki, Jacqui White, Mélanie A. Eckersley-Maslin, Sarah A. Teichmann, Wolf Reik, Beiyuan Fu, David Ryan, Liming Lu, Berthold Göttgens, Juexuan Wang, Lia S. Campos, Aleksandra A. Kolodziejczyk, Zhen Zhong, James Bussell, Yong Yu, Adam C. Wilkinson, Patrick P.L. Tam, Xi Chen, Yosuke Tanaka, Pentao Liu, Michael Woods, Cui Wang, Wei Wang, Xuefei Gao, Jian Yang, Zhexin Zhu, Hiromitsu Nakauchi, Liliana Antunes, Fengtang Yang, Ramiro Ramirez-Solis, Jason C.H. Tsang, Xiangang Zou, and Guocheng Lan
- Subjects
0301 basic medicine ,Epigenomics ,Male ,Pluripotent Stem Cells ,Blastomeres ,Somatic cell ,Placenta ,Biology ,Germline ,Article ,Epigenesis, Genetic ,Transcriptome ,03 medical and health sciences ,Mice ,Single-cell analysis ,Pregnancy ,medicine ,Animals ,Cell Lineage ,Blastocyst ,Induced pluripotent stem cell ,Cells, Cultured ,Multidisciplinary ,Chimera ,Endoderm ,Mouse Embryonic Stem Cells ,Embryo, Mammalian ,Embryonic stem cell ,Cell biology ,Trophoblasts ,030104 developmental biology ,medicine.anatomical_structure ,embryonic structures ,Female ,Stem cell ,Single-Cell Analysis - Abstract
Mouse embryonic stem cells derived from the epiblast1 contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm2 upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species.
- Published
- 2017
19. Establishment in Culture of Expanded Potential Stem Cells
- Author
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Xuefei Gao, CJ Tsang, James Bussell, Yosuke Tanaka, David Ryan, Mélanie A. Eckersley-Maslin, Adam C. Wilkinson, Pentao Liu, A Kolodziejczyk, Michael Woods, G Lan, Zhexin Zhu, Wei Wang, Sarah A. Teichmann, Jian Yang, Liliana Antunes, Berthold Göttgens, Fengtang Yang, Lia S. Campos, Juexuan Wang, Hiromitsu Nakauchi, Hideki Masaki, Cui Wang, Z Zhong, L Lu, Yong Yu, Jacqui White, Ramiro Ramirez-Solis, Wolf Reik, Beiyuan Fu, and X Zou
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Genetics ,0303 health sciences ,Somatic cell ,Embryoid body ,Biology ,Embryonic stem cell ,Cell biology ,Endothelial stem cell ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,embryonic structures ,medicine ,Blastocyst ,Stem cell ,Reprogramming ,reproductive and urinary physiology ,030217 neurology & neurosurgery ,030304 developmental biology ,Adult stem cell - Abstract
Mouse embryonic stem cells are derived fromin vitroexplantation of blastocyst epiblasts1,2and contribute to both the somatic lineage and germline when returned to the blastocyst3but are normally excluded from the trophoblast lineage and primitive endoderm4–6. Here, we report that cultures of expanded potential stem cells (EPSCs) can be established from individual blastomeres, by direct conversion of mouse embryonic stem cells (ESCs) and by genetically reprogramming somatic cells. Remarkably, a single EPSC contributes to the embryo proper and placenta trophoblasts in chimeras. Critically, culturing EPSCs in a trophoblast stem cell (TSC) culture condition permits direct establishment of TSC lines without genetic modification. Molecular analyses including single cell RNA-seq reveal that EPSCs share cardinal pluripotency features with ESCs but have an enriched blastomere transcriptomic signature and a dynamic DNA methylome. These proof-of-concept results open up the possibility of establishing cultures of similar stem cells in other mammalian species.
- Published
- 2017
20. Gene body methylation of the dimethylarginine dimethylamino-hydrolase 2 (Ddah2) gene is an epigenetic biomarker for neural stem cell differentiation
- Author
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Marlis Herberth, Florian Eckhardt, Peri Tate, Liselotte Bäckdahl, Lia S. Campos, Stephan Beck, Gareth A. Wilson, and Rene Cortese
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Neurons ,Regulation of gene expression ,Genetics ,Cancer Research ,Epigenetic regulation of neurogenesis ,Stem Cells ,Cellular differentiation ,Gene Expression ,Cell Differentiation ,DNA Methylation ,Biology ,Amidohydrolases ,Cell Line ,Epigenesis, Genetic ,Epigenetics of physical exercise ,DNA methylation ,Epigenetics ,Molecular Biology ,RNA-Directed DNA Methylation ,Biomarkers ,Epigenomics - Abstract
DNA methylation is an important epigenetic mark that is involved in the regulation of many cellular processes such as gene expression, genomic imprinting and silencing of repetitive elements. Because of their ability to cause and capture phenotypic plasticity, epigenetic marks such as DNA methylation represent potential biomarkers to distinguish between different types of tissues and stages of differentiation. Here, we have identified differential DNA methylation in the gene body of the nitric oxide inhibitor Ddah2 that discriminates embryonic stem cells from neural stem cells and is positively correlated with differential gene expression.
- Published
- 2009
21. Neurospheres: Insights into neural stem cell biology
- Author
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Lia S. Campos
- Subjects
Neurons ,Cell Survival ,Stem Cells ,Biology ,Matrix (biology) ,In vitro ,Neural stem cell ,nervous system diseases ,Extracellular matrix ,Cellular and Molecular Neuroscience ,nervous system ,Neurosphere ,Cell Adhesion ,Animals ,Humans ,biological phenomena, cell phenomena, and immunity ,Signal transduction ,Cell adhesion ,Neuroscience ,reproductive and urinary physiology ,Cell survival ,Signal Transduction - Abstract
Neural stem cells (NSC) are a tissue-specific subtype of self-renewing and multipotent cells that can give rise to all neural populations. In this review, the importance of maintaining cell-cell contacts in the study of NSC is highlighted, and data obtained from some crucial single-cell studies is compared to results obtained from neurospheres, where aggregates of NSC are grown in suspension. In particular, results that indicate how this culture system may be well suited to analyze NSC plasticity, cell-cell, and cell-extracellular matrix (ECM) interactions are pointed out, and the hypothesis that cell-cell and cell-ECM contacts may be essential for NSC maintenance, survival, and proliferation is highlighted. Finally, it is suggested that neurospheres might play a role in the study of context-dependent behavior of NSC in niches by providing a system where NSC can be challenged chemically or biologically and analyzed in vitro, in a time- and context-dependent manner.
- Published
- 2004
22. Evidence for astrocyte heterogeneity: A distinct subpopulation of protoplasmic-like glial cells is detected in transgenic mice expressingLmo1-lacZ
- Author
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Lia S. Campos
- Subjects
Central Nervous System ,Genetically modified mouse ,Cell type ,Transgene ,Central nervous system ,Mice, Transgenic ,Biology ,Mice ,Cellular and Molecular Neuroscience ,Genes, Reporter ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,Cell Lineage ,Gliosis ,Nuclear protein ,Oncogene Proteins ,Reporter gene ,Stem Cells ,Nuclear Proteins ,Cell Differentiation ,LIM Domain Proteins ,beta-Galactosidase ,Cell biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Lac Operon ,Neurology ,Astrocytes ,Brain Injuries ,Neuroglia ,Neuroscience ,Biomarkers ,Transcription Factors ,Astrocyte - Abstract
The adult mammalian central nervous system (CNS) contains a large number of different cell types, which arise from the ventricular (VZ) and subventricular zones during embryonic development. In this study, we used a transgenic mouse expressing Lmo1-LacZ from a randomly inserted promoter/reporter gene construct to identify a glial subpopulation. LMO1 is an LIM domain-containing protein, thought to act in protein-protein interactions. We found first that in the adult transgenic CNS, beta-galactosidase (beta-gal) was expressed in a specific subpopulation of protoplasmic-like cells, which did not express detectable levels of glial fibrilary acidic protein unless a lesion was produced. Secondly, during development, beta-gal(+) cells were found arising from discrete regions of the VZ. Taken together, these results identify a subpopulation of protoplasmic glial cells in the adult CNS and suggest that they arise from a restricted VZ region during CNS development.
- Published
- 2003
23. Quenching autofluorescence in tissue immunofluorescence
- Author
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Yvette Hooks, Pentao Liu, Helen E. Skelton, Jian Yang, Lia S. Campos, William Mansfield, and Fengtang Yang
- Subjects
0301 basic medicine ,medicine.diagnostic_test ,business.industry ,Medicine (miscellaneous) ,Texas Red ,Immunofluorescence ,medicine.disease ,Molecular biology ,General Biochemistry, Genetics and Molecular Biology ,3. Good health ,03 medical and health sciences ,chemistry.chemical_compound ,Autofluorescence ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Placenta ,medicine ,Trypan blue ,Sudan Black B ,Teratoma ,Stem cell ,business - Abstract
Background: Immunofluorescence (IF) is one of the most important techniques where fluorochromes conjugated to antibodies are used to detect specific proteins or antigens. In tissue sections, autofluorescence (AF) can lead to poor quality images that impair assessment. The placenta is a pivotal extra-embryonic organ in embryo development, where trophoblasts make up a large proportion of the cells. Teratoma formation is one of the critical assays for pluripotent stem cells. Methods: We tested whether ultraviolet (UV), ammonia (NH3), copper (II) sulfate (CuSO4), Trypan Blue (TB), Sudan Black B (SB), TrueBlack™ Lipofusin Autofluorescence Quencher (TLAQ) and combinations of these treatments could reduce AF in paraffin and frozen sections of placenta and teratoma in FITC, Texas Red and Cy5.5 channels. Results: We found that UV, NH3, TB and CuSO4 quenched AF to some extent in different tissue and filters, but increased AF in Texas Red or Cy5.5 channels in some cases. SB and TLQA exhibited the most consistent effects on decreasing AF, though TLQA reduced the overall IF signal in placenta sections. Not all combined treatments further reduced AF in both placenta and teratoma sections. Conclusions: SB and TLAQ can effectively quench AF in placenta and teratoma IF.
- Published
- 2017
24. MiR-25 regulates Wwp2 and Fbxw7 and promotes reprogramming of mouse fibroblast cells to iPSCs
- Author
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Lia S. Campos, Dong Lu, Julia Siede, Anton J. Enright, Elena Vigorito, Pentao Liu, Matthew P. Davis, Wei Wang, Cei Abreu-Goodger, William C. Skarnes, Ian Dunham, Vigorito, Elena [0000-0001-6230-3849], Enright, Anton [0000-0002-6090-3100], and Apollo - University of Cambridge Repository
- Subjects
F-Box-WD Repeat-Containing Protein 7 ,Somatic cell ,Ubiquitin-Protein Ligases ,Induced Pluripotent Stem Cells ,lcsh:Medicine ,WWP2 ,Biology ,Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Nucleic Acids ,Molecular Cell Biology ,microRNA ,Gene expression ,Genetics ,Animals ,lcsh:Science ,Induced pluripotent stem cell ,Embryonic Stem Cells ,030304 developmental biology ,Regulation of gene expression ,0303 health sciences ,Multidisciplinary ,Base Sequence ,Stem Cells ,F-Box Proteins ,lcsh:R ,Computational Biology ,Transfection ,Fibroblasts ,Cellular Reprogramming ,Cell biology ,MicroRNAs ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,RNA ,lcsh:Q ,Epigenetics ,Cellular Types ,Reprogramming ,Research Article ,Developmental Biology - Abstract
BACKGROUND: miRNAs are a class of small non-coding RNAs that regulate gene expression and have critical functions in various biological processes. Hundreds of miRNAs have been identified in mammalian genomes but only a small number of them have been functionally characterized. Recent studies also demonstrate that some miRNAs have important roles in reprogramming somatic cells to induced pluripotent stem cells (iPSCs). METHODS: We screened 52 miRNAs cloned in a piggybac (PB) vector for their roles in reprogramming of mouse embryonic fibroblast cells to iPSCs. To identify targets of miRNAs, we made Dgcr8-deficient embryonic stem (ES) cells and introduced miRNA mimics to these cells, which lack miRNA biogenesis. The direct target genes of miRNA were identified through global gene expression analysis and target validation. RESULTS AND CONCLUSION: We found that over-expressing miR-25 or introducing miR-25 mimics enhanced production of iPSCs. We identified a number of miR-25 candidate gene targets. Of particular interest were two ubiquitin ligases, Wwp2 and Fbxw7, which have been proposed to regulate Oct4, c-Myc and Klf5, respectively. Our findings thus highlight the complex interplay between miRNAs and transcription factors involved in reprogramming, stem cell self-renewal and maintenance of pluripotency.
- Published
- 2012
25. PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice
- Author
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Dong Lu, Ruby Banerjee, Juan Cadiñanos, Alexander Strong, Pentao Liu, Nathalie Conte, George S. Vassiliou, Wei Wang, Stephen Rice, Jorge de la Rosa, Allan Bradley, Fang Tang Yang, Meng Amy Li, Lia S. Campos, Kosuke Yusa, Roland Rad, Peter R. Ellis, and Lena Rad
- Subjects
Genetics ,Transposable element ,Multidisciplinary ,Transgene ,fungi ,Mutagenesis (molecular biology technique) ,Mice, Transgenic ,Oncogenes ,Biology ,Sleeping Beauty transposon system ,Article ,Insertional mutagenesis ,Mice, Inbred C57BL ,Mice ,Mutagenesis, Insertional ,Neoplasms ,DNA Transposable Elements ,Animals ,Transposon mutagenesis ,Genetic Testing ,Promoter Regions, Genetic ,Gene ,Transposase ,Genes, Neoplasm - Abstract
Transposons are mobile DNA segments that can disrupt gene function by inserting in or near genes. Here, we show that insertional mutagenesis by the PiggyBac transposon can be used for cancer gene discovery in mice. PiggyBac transposition in genetically engineered transposon-transposase mice induced cancers whose type (hematopoietic versus solid) and latency were dependent on the regulatory elements introduced into transposons. Analysis of 63 hematopoietic tumors revealed that PiggyBac is capable of genome-wide mutagenesis. The PiggyBac screen uncovered many cancer genes not identified in previous retroviral or Sleeping Beauty transposon screens, including Spic, which encodes a PU.1-related transcription factor, and Hdac7, a histone deacetylase gene. PiggyBac and Sleeping Beauty have different integration preferences. To maximize the utility of the tool, we engineered 21 mouse lines to be compatible with both transposon systems in constitutive, tissue- or temporal-specific mutagenesis. Mice with different transposon types, copy numbers, and chromosomal locations support wide applicability.
- Published
- 2010
26. Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion
- Author
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Francesco Colucci, Lia S. Campos, Shannon Burke, Bee Ling Ng, Dong Lu, Gordon Dougan, Neal G. Copeland, Xiongfeng Chen, Brian J. P. Huntly, Bertie Gottgens, Pentao Liu, Juexuan Wang, David Goulding, Mariaestela Ortiz, Peng Li, Nancy A. Jenkins, and Song Choon Lee
- Subjects
Cytotoxicity, Immunologic ,T cell ,Receptors, Antigen, T-Cell, alpha-beta ,T-Lymphocytes ,Melanoma, Experimental ,Biology ,Article ,Natural killer cell ,Interleukin 21 ,Mice ,Antigen ,Cell Line, Tumor ,medicine ,Animals ,Cell Lineage ,Gene Knock-In Techniques ,Cells, Cultured ,Interleukin 3 ,Oligonucleotide Array Sequence Analysis ,Mice, Knockout ,Precursor Cells, T-Lymphoid ,Multidisciplinary ,Innate immune system ,Gene Expression Profiling ,Lymphopoiesis ,Tumor Suppressor Proteins ,Gene Expression Regulation, Developmental ,T lymphocyte ,Acquired immune system ,Molecular biology ,Coculture Techniques ,Cell biology ,Killer Cells, Natural ,Mice, Inbred C57BL ,Repressor Proteins ,Tamoxifen ,medicine.anatomical_structure ,Genes, T-Cell Receptor beta ,Stromal Cells ,Gene Deletion ,Signal Transduction - Abstract
One Two TT cells develop in the thymus, where they proceed through several developmental stages, losing alternative lineage potential as they progress. The molecular regulation of this developmental process, however, is not fully understood (see the Perspective byDi Santo).P. Liet al.(p.85, published online 10 June),L. Liet al.(p.89), andIkawaet al.(p.93) now identify expression of the zinc finger transcription factorBcl11bas the earliest checkpoint in T cell development in mice. Genetic deletion ofBcl11bin developing T cells inhibited commitment to the T cell lineage. Under conditions that should have stimulated T lineage differentiation,Bcl11b-deficient T cell progenitors failed to up-regulate genes associated with lineage-committed T cells and maintained stem cell– and progenitor cell–associated gene expression. In both developing and committed T cells, loss ofBcl11bresulted in the generation of cells that resembled natural killer (NK) cells in both phenotype and function. These NK-like cells could be expanded easily in vitro and possessed antitumor cytotoxicity, but they did not exhibit cytotoxicity against normal cells and were not tumorigenic. Because T cells are much easier to obtain from human patients than NK cells, deletion ofBcl11bin T cells may thus provide a source of easy-to-grow NK cells for cell-based antitumor therapies.
- Published
- 2010
27. A DNA transposon-based approach to validate oncogenic mutations in the mouse
- Author
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Mariaestela Ortiz, Lia S. Campos, Adam J. Dupuy, Haydn M. Prosser, Pentao Liu, Neal G. Copeland, Nancy A. Jenkins, Qin Su, Takuro Nakamura, Madhuri Warren, and Allan Bradley
- Subjects
Transposable element ,DNA, Complementary ,DNA Mutational Analysis ,Transposases ,Genomics ,Mice, Transgenic ,Biology ,Genome ,Mice ,Neoplasms ,Animals ,Humans ,Cloning, Molecular ,Transposons as a genetic tool ,Gene ,Transposase ,Oligonucleotide Array Sequence Analysis ,Genetics ,Multidisciplinary ,Base Sequence ,Genome, Human ,Genetic Complementation Test ,DNA, Neoplasm ,Oncogenes ,Biological Sciences ,Sleeping Beauty transposon system ,Mutation ,DNA Transposable Elements ,Human genome - Abstract
Large-scale cancer genome projects will soon be able to sequence many cancer genomes to comprehensively identify genetic changes in human cancer. Genome-wide association studies have also identified putative cancer associated loci. Functional validation of these genetic mutations in vivo is becoming a challenge. We describe here a DNA transposon-based platform that permits us to explore the oncogenic potential of genetic mutations in the mouse. Briefly, promoter-less human cancer gene cDNAs were first cloned into Sleeping Beauty ( SB ) transposons. DNA transposition in the mouse that carried both the transposons and the SB transposase made it possible for the cDNAs to be expressed from an appropriate endogenous genomic locus and in the relevant cell types for tumor development. Consequently, these mice developed a broad spectrum of tumors at very early postnatal stages. This technology thus complements the large-scale cancer genome projects.
- Published
- 2008
28. Notch, epidermal growth factor receptor, and beta1-integrin pathways are coordinated in neural stem cells
- Author
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Verdon Taylor, Laurence Decker, William C. Skarnes, and Lia S. Campos
- Subjects
Central Nervous System ,Time Factors ,Caveolin 1 ,Notch signaling pathway ,Biochemistry ,Receptor tyrosine kinase ,Mice ,Membrane Microdomains ,Cell surface receptor ,Animals ,Immunoprecipitation ,Epidermal growth factor receptor ,Growth Substances ,Molecular Biology ,Cells, Cultured ,Glutathione Transferase ,Cell Nucleus ,Neurons ,Manganese ,biology ,Receptors, Notch ,Reverse Transcriptase Polymerase Chain Reaction ,Integrin beta1 ,Stem Cells ,Brain ,Cell Biology ,Immunohistochemistry ,Neural stem cell ,Cell biology ,Extracellular Matrix ,ErbB Receptors ,Mice, Inbred C57BL ,Notch proteins ,Microscopy, Fluorescence ,Hes3 signaling axis ,biology.protein ,Fibroblast Growth Factor 2 ,Signal transduction ,Protein Binding ,Signal Transduction - Abstract
Notch1 and beta1-integrins are cell surface receptors involved in the recognition of the niche that surrounds stem cells through cell-cell and cell-extracellular matrix interactions, respectively. Notch1 is also involved in the control of cell fate choices in the developing central nervous system (Lewis, J. (1998) Semin. Cell Dev. Biol. 9, 583-589). Here we report that Notch and beta1-integrins are co-expressed and that these proteins cooperate with the epidermal growth factor receptor in neural progenitors. We describe data that suggests that beta1-integrins may affect Notch signaling through 1) physical interaction (sequestration) of the Notch intracellular domain fragment by the cytoplasmic tail of the beta1-integrin and 2) affecting trafficking of the Notch intracellular domain via caveolin-mediated mechanisms. Our findings suggest that caveolin 1-containing lipid rafts play a role in the coordination and coupling of beta1-integrin, Notch1, and tyrosine kinase receptor signaling pathways. We speculate that this will require the presence of the adequate beta1-activating extracellular matrix or growth factors in restricted regions of the central nervous system and namely in neurogenic niches.
- Published
- 2005
29. Beta1 integrins and neural stem cells: making sense of the extracellular environment
- Author
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Lia S. Campos
- Subjects
Cerebral Cortex ,Neurons ,biology ,Cellular differentiation ,Integrin beta1 ,Stem Cells ,Integrin ,Cell Differentiation ,Embryonic stem cell ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Neural stem cell ,Cortex (botany) ,Extracellular Matrix ,Extracellular matrix ,Mice ,Microscopy, Fluorescence ,Cell Movement ,Immunology ,biology.protein ,Extracellular ,Animals ,Humans ,Stem cell ,Neuroscience - Abstract
Neural Stem Cells (NSC) are present in the developing and adult CNS. In both the embryonic and adult neurogenic regions, beta1 integrins may act as sensors for the changing extracellular matrix. Here we highlight the integrative functions that beta1 integrins may play in the "niche" by regulating NSC growth factor responsiveness in a timely and spatially controlled manner. beta1 integrins may provide NSC with the capacity to react to a dynamic "niche", and to respond adequately by either remaining as stem cells or by differentiating and migrating away to shape the developing cortex.
- Published
- 2005
30. Beta1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance
- Author
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Reinhard Fässler, Dino P. Leone, João B. Relvas, Ueli Suter, Lia S. Campos, Cord Brakebusch, and Charles ffrench-Constant
- Subjects
Time Factors ,MAP Kinase Signaling System ,Blotting, Western ,Cell Culture Techniques ,Cell Separation ,Biology ,Models, Biological ,Epithelium ,Mice ,Neurosphere ,Animals ,Phosphorylation ,Coloring Agents ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Cells, Cultured ,Mice, Knockout ,Neurons ,Integrin beta1 ,Stem Cells ,Epithelial Cells ,Flow Cytometry ,Embryonic stem cell ,Immunohistochemistry ,Neural stem cell ,Cell biology ,Extracellular Matrix ,Fibronectins ,Neuroepithelial cell ,Endothelial stem cell ,Bromodeoxyuridine ,Laminin ,Stem cell ,Developmental Biology ,Adult stem cell ,Signal Transduction - Abstract
The emerging evidence that stem cells develop in specialised niches highlights the potential role of environmental factors in their regulation. Here we examine the role of beta1 integrin/extracellular matrix interactions in neural stem cells. We find high levels of beta1 integrin expression in the stem-cell containing regions of the embryonic CNS, with associated expression of the laminin alpha2 chain. Expression levels of laminin alpha2 are reduced in the postnatal CNS, but a population of cells expressing high levels of beta1 remains. Using neurospheres - aggregate cultures, derived from single stem cells, that have a three-dimensional architecture that results in the localisation of the stem cell population around the edge of the sphere - we show directly that beta1 integrins are expressed at high levels on neural stem cells and can be used for their selection. MAPK, but not PI3K, signalling is required for neural stem cell maintenance, as assessed by neurosphere formation, and inhibition or genetic ablation of beta1 integrin using cre/lox technology reduces the level of MAPK activity. We conclude that integrins are therefore an important part of the signalling mechanisms that control neural stem cell behaviour in specific areas of the CNS.
- Published
- 2004
31. Cell of the month: Differentiating mouse embryonic stem cells
- Author
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Lia S. Campos
- Subjects
KOSR ,Homeobox protein NANOG ,Amniotic stem cells ,Cell Biology ,Embryoid body ,Biology ,Stem cell ,Induced pluripotent stem cell ,Embryonic stem cell ,Adult stem cell ,Cell biology - Published
- 2004
32. Polygenic in vivovalidation of cancer mutations using transposons
- Author
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Kenneth L. Scott, Pentao Liu, John Gamble, Dong Lu, Lia S. Campos, Lynda Chin, Stuart McLaren, Juexuan Wang, Keiran Raine, Su K.it Chew, Adam Butler, Adam Collinson, David T. Jones, Jon W. Teague, Sarah O’Meara, Andrew Menzies, Abdel Saci, P. Andrew Futreal, and Jonathan Hinton
- Subjects
Transposable element ,Multifactorial Inheritance ,Carcinogenesis ,Method ,Genomics ,Mice, Transgenic ,Mice, SCID ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Mice, Inbred NOD ,Neoplasms ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Gene ,Cells, Cultured ,Genetic Association Studies ,030304 developmental biology ,Genetics ,0303 health sciences ,Bacterial artificial chromosome ,Mutation ,Cancer ,medicine.disease ,Human genetics ,Coculture Techniques ,030220 oncology & carcinogenesis ,DNA Transposable Elements ,Neoplasm Transplantation - Abstract
The in vivo validation of cancer mutations and genes identified in cancer genomics is resource-intensive because of the low throughput of animal experiments. We describe a mouse model that allows multiple cancer mutations to be validated in each animal line. Animal lines are generated with multiple candidate cancer mutations using transposons. The candidate cancer genes are tagged and randomly expressed in somatic cells, allowing easy identification of the cancer genes involved in the generated tumours. This system presents a useful, generalised and efficient means for animal validation of cancer genes. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0455-6) contains supplementary material, which is available to authorized users.
- Full Text
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