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2. De novo hematopoiesis from the fetal lung

Author

Yeung, Anthony K., Villacorta-Martin, Carlos, Lindstrom-Vautrin, Jonathan, Belkina, Anna C., Vanuytsel, Kim, Dowrey, Todd W., Ysasi, Alexandra B., Bawa, Pushpinder, Wang, Feiya, Vrbanac, Vladimir, Mostoslavsky, Gustavo, Balazs, Alejandro B., and Murphy, George J.

Published
2023
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3. Organoids Model Transcriptional Hallmarks of Oncogenic KRAS Activation in Lung Epithelial Progenitor Cells

Author

Dost, Antonella FM, Moye, Aaron L, Vedaie, Marall, Tran, Linh M, Fung, Eileen, Heinze, Dar, Villacorta-Martin, Carlos, Huang, Jessie, Hekman, Ryan, Kwan, Julian H, Blum, Benjamin C, Louie, Sharon M, Rowbotham, Samuel P, Sainz de Aja, Julio, Piper, Mary E, Bhetariya, Preetida J, Bronson, Roderick T, Emili, Andrew, Mostoslavsky, Gustavo, Fishbein, Gregory A, Wallace, William D, Krysan, Kostyantyn, Dubinett, Steven M, Yanagawa, Jane, Kotton, Darrell N, and Kim, Carla F

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Rare Diseases, Stem Cell Research - Induced Pluripotent Stem Cell, Lung Cancer, Cancer, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Lung, Biotechnology, 2.1 Biological and endogenous factors, Animals, Humans, Induced Pluripotent Stem Cells, Mice, Organoids, Proteomics, Proto-Oncogene Proteins p21(ras), KRAS, alveolar, developmental programs, early-stage lung cancer, iPSC, loss of differentiation, organoid, single-cell RNA sequencing, stage IA lung adenocarcinoma, tumor progression, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Mutant KRAS is a common driver in epithelial cancers. Nevertheless, molecular changes occurring early after activation of oncogenic KRAS in epithelial cells remain poorly understood. We compared transcriptional changes at single-cell resolution after KRAS activation in four sample sets. In addition to patient samples and genetically engineered mouse models, we developed organoid systems from primary mouse and human induced pluripotent stem cell-derived lung epithelial cells to model early-stage lung adenocarcinoma. In all four settings, alveolar epithelial progenitor (AT2) cells expressing oncogenic KRAS had reduced expression of mature lineage identity genes. These findings demonstrate the utility of our in vitro organoid approaches for uncovering the early consequences of oncogenic KRAS expression. This resource provides an extensive collection of datasets and describes organoid tools to study the transcriptional and proteomic changes that distinguish normal epithelial progenitor cells from early-stage lung cancer, facilitating the search for targets for KRAS-driven tumors.

Published
2020

4. Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program

Author

Kanchan, Kanika, Iyer, Kruthika, Yanek, Lisa R, Carcamo-Orive, Ivan, Taub, Margaret A, Malley, Claire, Baldwin, Kristin, Becker, Lewis C, Broeckel, Ulrich, Cheng, Linzhao, Cowan, Chad, D'Antonio, Matteo, Frazer, Kelly A, Quertermous, Thomas, Mostoslavsky, Gustavo, Murphy, George, Rabinovitch, Marlene, Rader, Daniel J, Steinberg, Martin H, Topol, Eric, Yang, Wenli, Knowles, Joshua W, Jaquish, Cashell E, Ruczinski, Ingo, and Mathias, Rasika A

Subjects
Biological Sciences, Genetics, Stem Cell Research, Stem Cell Research - Induced Pluripotent Stem Cell, Human Genome, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Cancer, Biotechnology, 2.1 Biological and endogenous factors, Cell Differentiation, DNA Copy Number Variations, DNA-Binding Proteins, Genomic Instability, Genomics, Humans, Induced Pluripotent Stem Cells, National Heart, Lung, and Blood Institute (U.S.), United States, hiPSCs, Structural integrity, GWAS, VanillaICE, Oncogenes, Tumor suppressor genes, Medical and Health Sciences, Developmental Biology, Medical biotechnology, Oncology and carcinogenesis
Abstract

Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models.

Published
2020

5. Isolation, Maintenance and Differentiation of Primary Tracheal Basal Cells from Adult Rhesus Macaque.

Author

Engler, Anna E, Mostoslavsky, Gustavo, Miller, Lisa, and Rock, Jason R

Subjects
air–liquid interface, primary culture, rhesus macaque, tracheal basal cells, tracheospheres
Abstract

In this report, we describe methodologies for the isolation and culture of primary rhesus macaque tracheal basal cells, their cryopreservation, long term storage and differentiation. These are comparable to state-of-the-art protocols that have been developed for mouse and human airway basal cells. This method is based on the use of proprietary media, providing an easily reproducible and applicable protocol for usage in biosafety level 2 (BSL2) settings. Tracheas from rhesus macaques were isolated after animal euthanasia and subjected to enzymatic digestion overnight. Cells of the epithelial layer were scraped off of the trachea for cell culture. Twenty-four hours after plating basal cells had attached and nonadherent cells were removed. First passages of basal cells can be frozen for early passage storage in liquid nitrogen or propagated and differentiated on an air-liquid interface and in a tracheosphere assay up to passage seven. This protocol provides a platform for the analysis of basal cells from a close evolutionary relative to humans.

Published
2019

7. Ebola virus infection induces a delayed type I IFN response in bystander cells and the shutdown of key liver genes in human iPSC-derived hepatocytes

Author

Scoon, Whitney A., Mancio-Silva, Liliana, Suder, Ellen L., Villacorta-Martin, Carlos, Lindstrom-Vautrin, Jonathan, Bernbaum, John G., Mazur, Steve, Johnson, Reed F., Olejnik, Judith, Flores, Elizabeth Y., Mithal, Aditya, Wang, Feiya, Hume, Adam J., Kaserman, Joseph E., March-Riera, Sandra, Wilson, Andrew A., Bhatia, Sangeeta N., Mühlberger, Elke, and Mostoslavsky, Gustavo

Published
2022
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8. Long-term analysis of antibodies elicited by SPUTNIK V: A prospective cohort study in Tucumán, Argentina

Author

Chahla, Rossana Elena, Tomas-Grau, Rodrigo Hernán, Cazorla, Silvia Inés, Ploper, Diego, Vera Pingitore, Esteban, López, Mónica Aguilar, Aznar, Patricia, Alcorta, María Elena, Vélez, Eva María del Mar, Stagnetto, Agustín, Ávila, César Luís, Maldonado-Galdeano, Carolina, Socias, Sergio Benjamín, Heinze, Dar, Navarro, Silvia Adriana, Llapur, Conrado Juan, Costa, Dardo, Flores, Isolina, Edelstein, Alexis, Kowdle, Shreyas, Perandones, Claudia, Lee, Benhur, Apfelbaum, Gabriela, Mostoslavsky, Raúl, Mostoslavsky, Gustavo, Perdigón, Gabriela, and Chehín, Rosana Nieves

Published
2022
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9. A multimodal iPSC platform for cystic fibrosis drug testing

Author

Berical, Andrew, Lee, Rhianna E., Lu, Junjie, Beermann, Mary Lou, Le Suer, Jake A., Mithal, Aditya, Thomas, Dylan, Ranallo, Nicole, Peasley, Megan, Stuffer, Alex, Bukis, Katherine, Seymour, Rebecca, Harrington, Jan, Coote, Kevin, Valley, Hillary, Hurley, Killian, McNally, Paul, Mostoslavsky, Gustavo, Mahoney, John, Randell, Scott H., and Hawkins, Finn J.

Published
2022
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10. Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment

Author

Vanuytsel, Kim, Villacorta-Martin, Carlos, Lindstrom-Vautrin, Jonathan, Wang, Zhe, Garcia-Beltran, Wilfredo F., Vrbanac, Vladimir, Parsons, Dylan, Lam, Evan C., Matte, Taylor M., Dowrey, Todd W., Kumar, Sara S., Li, Mengze, Wang, Feiya, Yeung, Anthony K., Mostoslavsky, Gustavo, Dries, Ruben, Campbell, Joshua D., Belkina, Anna C., Balazs, Alejandro B., and Murphy, George J.

Published
2022
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12. Reconstructed Single-Cell Fate Trajectories Define Lineage Plasticity Windows during Differentiation of Human PSC-Derived Distal Lung Progenitors

Author

Hurley, Killian, Ding, Jun, Villacorta-Martin, Carlos, Herriges, Michael J., Jacob, Anjali, Vedaie, Marall, Alysandratos, Konstantinos D., Sun, Yuliang L., Lin, Chieh, Werder, Rhiannon B., Huang, Jessie, Wilson, Andrew A., Mithal, Aditya, Mostoslavsky, Gustavo, Oglesby, Irene, Caballero, Ignacio S., Guttentag, Susan H., Ahangari, Farida, Kaminski, Naftali, Rodriguez-Fraticelli, Alejo, Camargo, Fernando, Bar-Joseph, Ziv, and Kotton, Darrell N.

Published
2020
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13. Risks Associated With Lentiviral Vector Exposures and Prevention Strategies

Author

Schlimgen, Ryan, Howard, John, Wooley, Dawn, Thompson, Maureen, Baden, Lindsey R, Yang, Otto O, Christiani, David C, Mostoslavsky, Gustavo, Diamond, David V, Duane, Elizabeth Gilman, Byers, Karen, Winters, Thomas, Gelfand, Jeffrey A, Fujimoto, Gary, Hudson, T Warner, and Vyas, Jatin M

Subjects
Commerce, Management, Tourism and Services, Epidemiology, Public Health, Health Sciences, Human Resources and Industrial Relations, Genetics, Clinical Research, Patient Safety, Prevention, Clinical Trials and Supportive Activities, Biotechnology, HIV/AIDS, 2.2 Factors relating to the physical environment, Evaluation of treatments and therapeutic interventions, Aetiology, 6.1 Pharmaceuticals, Good Health and Well Being, Genetic Vectors, Health Personnel, Humans, Lentivirus, Occupational Exposure, Occupational Health, Risk Assessment, Nursing, Public Health and Health Services, Environmental & Occupational Health, Human resources and industrial relations, Public health
Abstract

Lentiviral vectors (LVVs) are powerful genetic tools that are being used with greater frequency in biomedical laboratories and clinical trials. Adverse events reported from initial clinical studies provide a basis for risk assessment of occupational exposures, yet many questions remain about the potential harm that LVVs may cause. We review those risks and provide a framework for principal investigators, Institutional Biosafety Committees, and occupational health professionals to assess and communicate the risks of exposure to staff. We also provide recommendations to federal research and regulatory agencies for tracking LVV exposures to evaluate long-term outcomes. U.S. Food and Drug Administration approved antiviral drugs for HIV have theoretical benefits in LVV exposures, although evidence to support their use is currently limited. If treatment is appropriate, we recommend a 7-day treatment with an integrase inhibitor with or without a reverse transcriptase inhibitor within 72 hours of exposure.

Published
2016

14. A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels

Author

Casalia, Mariana L., Casabona, Juan Cruz, García, Corina, Cavaliere Candedo, Verónica, Quintá, Héctor Ramiro, Farías, María Isabel, Gonzalez, Joaquín, Gonzalez Morón, Dolores, Córdoba, Marta, Consalvo, Damian, Mostoslavsky, Gustavo, Urbano, Francisco J., Pasquini, Juana, Murer, Mario Gustavo, Rela, Lorena, Kauffman, Marcelo A., and Pitossi, Fernando J.

Published
2021
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16. A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells

Author

Park, Seonmi, Gianotti-Sommer, Andreia, Molina-Estevez, Francisco Javier, Vanuytsel, Kim, Skvir, Nick, Leung, Amy, Rozelle, Sarah S., Shaikho, Elmutaz Mohammed, Weir, Isabelle, Jiang, Zhihua, Luo, Hong-Yuan, Chui, David H.K., Figueiredo, Maria Stella, Alsultan, Abdulraham, Al-Ali, Amein, Sebastiani, Paola, Steinberg, Martin H., Mostoslavsky, Gustavo, and Murphy, George J.

Published
2017
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19. Emergence of a Stage-Dependent Human Liver Disease Signature with Directed Differentiation of Alpha-1 Antitrypsin-Deficient iPS Cells

Author

Wilson, Andrew A., Ying, Lei, Liesa, Marc, Segeritz, Charis-Patricia, Mills, Jason A., Shen, Steven S., Jean, Jyhchang, Lonza, Geordie C., Liberti, Derek C., Lang, Alex H., Nazaire, Jean, Gower, Adam C., Müeller, Franz-Josef, Mehta, Pankaj, Ordóñez, Adriana, Lomas, David A., Vallier, Ludovic, Murphy, George J., Mostoslavsky, Gustavo, Spira, Avrum, Shirihai, Orian S., Ramirez, Maria I., Gadue, Paul, and Kotton, Darrell N.

Published
2015
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21. De Novo Hematopoiesis from the Fetal LUNG

Author

Yeung, Anthony K, primary, Villacorta-Martin, Carlos, additional, Lindstrom-Vautrin, Jonathan, additional, Belkina, Anna C, additional, Vanuytsel, Kim, additional, Dowrey, Todd, additional, Ysasi, Alexandra B, additional, Vrbanac, Vladimir, additional, Mostoslavsky, Gustavo, additional, Balazs, Alejandro, additional, and Murphy, George J, additional

Published
2022
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23. The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation

Author

Smith, Brenden W., Rozelle, Sarah S., Leung, Amy, Ubellacker, Jessalyn, Parks, Ashley, Nah, Shirley K., French, Deborah, Gadue, Paul, Monti, Stefano, Chui, David H.K., Steinberg, Martin H., Frelinger, Andrew L., Michelson, Alan D., Theberge, Roger, McComb, Mark E., Costello, Catherine E., Kotton, Darrell N., Mostoslavsky, Gustavo, Sherr, David H., and Murphy, George J.

Published
2013
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29. Variants in Interferon Lambda are Associated with Very Early Onset Inflammatory Bowel Disease

Author

Ouahed, Jodie D., primary, Broggi, Achille, additional, Glick, Abigail, additional, Haring, Robin T., additional, Field, Michael, additional, Chinnapen, Daniel, additional, Grey, Michael J., additional, Lencer, Wayne, additional, Steiner, Steven J., additional, Dennis-Heyward, Evida, additional, Shroyer, Noah, additional, Criss, Zachary, additional, Lin, Shih-Ching, additional, Zeng, Xi-Lei, additional, Crawford, Sue E., additional, Estes, Mary K., additional, Thiagarajah, Jay R., additional, Capilla, Amalia, additional, Scoon, Whitney, additional, Mostoslavsky, Gustavo, additional, Spence, Jason, additional, Klein, Christoph, additional, Muise, Aleixo M., additional, Horwitz, Bruce, additional, Zanoni, Ivan, additional, and Snapper, Scott B., additional

Published
2022
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32. DE-NOVO HEMATOPOIESIS FROM THE FETAL LUNG

Author

Yeung, Anthony K., primary, Villacorta-Martin, Carlos, additional, Lindstrom-Vautrin, Jonathan, additional, Belkina, Anna C., additional, Vanuytsel, Kim, additional, Dowrey, Todd W., additional, Ysasi, Alexandra B., additional, Vrbanac, Vladimir, additional, Mostoslavsky, Gustavo, additional, Balazs, Alejandro B., additional, and Murphy, George J., additional

Published
2022
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34. 3213 – MULTI-MODAL PROFILING OF HUMAN FETAL LIVER HEMATOPOIETIC STEM CELLS REVEALS THE MOLECULAR SIGNATURE OF ENGRAFTMENT

Author

Vanuytsel, Kim, primary, Villacorta-Martin, Carlos, additional, Lindstrom-Vautrin, Jonathan, additional, Wang, zhe, additional, Garcia-Beltran, Wilfredo, additional, Vrbanac, Vladimir, additional, Parsons, Dylan, additional, Lam, Evan, additional, Matte, Taylor, additional, Dowrey, Todd, additional, Kumar, sara, additional, Li, Mengze, additional, Wang, Feiya, additional, Yeung, Anthony, additional, Mostoslavsky, Gustavo, additional, Dries, Ruben, additional, Campbell, Joshua, additional, Belkina, Anna, additional, Balazs, Alejandro, additional, and Murphy, George, additional

Published
2022
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35. Longitudinal waning of mRNA vaccine-induced neutralizing antibodies against SARS-CoV-2 detected by an LFIA rapid test

Author

Wang, Qiao, Feng, Lili, Zhang, Haohai, Gao, Juehua, Mao, Changchuin, Landesman-Bollag, Esther, Mostoslavsky, Gustavo, Lunderberg, Justin M, Zheng, Weina, Hao, Shushun, and Gao, Wenda

Subjects
AcademicSubjects/SCI01030, rapid test, mRNA vaccine, SARS-CoV-2, Immunology, neutralizing antibody, Immunology and Allergy, Original Research Article, AcademicSubjects/SCI00100, LFIA
Abstract

While mRNA vaccines against SARS-CoV-2 were highly efficacious against severe illness and hospitalization, they seem to be less effective in preventing infection months after vaccination, especially with the Delta variant. Breakthrough infections might be due to higher infectivity of the variants, relaxed protective measures by the general public in “COVID-19 fatigue”, and/or waning immunity post-vaccination. Determining the neutralizing antibody levels in a longitudinal manner may address this issue, but technical complexity of classic assays precludes easy detection and quick answers. We developed a lateral flow immunoassay NeutraXpress™ (commercial name of the test kit by Antagen Diagnostics, Inc.), and tested fingertip blood samples of subjects receiving either Moderna or Pfizer vaccines at various time points. With this device, we confirmed the reported clinical findings that mRNA vaccine-induced neutralizing antibodies quickly wane after 3–6 months. Thus, using rapid tests to monitor neutralizing antibody status could help identify individuals at risk, prevent breakthrough infections and guide social behavior to curtail the spread of COVID-19. Statement of Significance. Mounting evidence suggests that mRNA vaccine-induced neutralizing antibody titres against SARS-CoV-2 wane in 3–6 months. Quick identification of fully vaccinated persons with high risk of breakthrough infections is key to control the COVID-19 pandemic. The described LFIA device having a control/sample dual-lane design serves this purpose with successful field-test data.

Published
2021

36. Elevated Humoral Immune Response to SARS-CoV-2 at High Altitudes Revealed by an Anti-RBD “In-House” ELISA

Author

Tomas-Grau, Rodrigo Hernán, primary, Ploper, Diego, additional, Ávila, César Luis, additional, Vera Pingitore, Esteban, additional, Maldonado Galdeano, Carolina, additional, Chaves, Silvina, additional, Socias, Sergio Benjamín, additional, Stagnetto, Agustín, additional, Navarro, Silvia Adriana, additional, Chahla, Rossana Elena, additional, Aguilar López, Mónica, additional, Llapur, Conrado Juan, additional, Aznar, Patricia, additional, Alcorta, María Elena, additional, Costas, Dardo, additional, Flores, Isolina, additional, Heinze, Dar, additional, Apfelbaum, Gabriela, additional, Mostoslavsky, Raul, additional, Mostoslavsky, Gustavo, additional, Cazorla, Silvia Inés, additional, Perdigón, Gabriela del Valle, additional, and Chehín, Rosana, additional

Published
2021
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38. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells

Author

Lafaille, Fabien G., Pessach, Itai M., Zhang, Shen-Ying, Ciancanelli, Michael J., Herman, Melina, Abhyankar, Avinash, Ying, Shui-Wang, Keros, Sotirios, Goldstein, Peter A., Mostoslavsky, Gustavo, Ordovas-Montanes, Jose, Jouanguy, Emmanuelle, Plancoulaine, Sabine, Tu, Edmund, Elkabetz, Yechiel, Muhsen, Saleh Al-, Tardieu, Marc, Schlaeger, Thorsten M., Daley, George Q., Abel, Laurent, Casanova, Jean-Laurent, Studer, Lorenz, and Notarangelo, Luigi D.

Subjects
Physiological aspects, Research, Health aspects, Virulence (Microbiology) -- Research -- Physiological aspects -- Health aspects, Toll-like receptors -- Physiological aspects -- Health aspects -- Research, Stem cells -- Physiological aspects -- Health aspects -- Research, Herpes simplex virus -- Physiological aspects -- Health aspects -- Research, Neurons -- Physiological aspects -- Health aspects -- Research
Abstract

Childhood HSE is a rare, life-threatening, central nervous system (CNS)-restricted complication of primary infection with HSV-1, an almost ubiquitous virus that is typically innocuous4. Children with HSE are not unusually [...], In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of toll-like receptor 3 (TLR3) immunity are prone to HSV-1 encephalitis (HSE) (1-3). We tested the hypothesis that the pathogenesis of HSE involves non-haematopoietic CNS-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were differentiated into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of interferon-β (IFN-β) and/or IFN-λ1 in response to stimulation by the dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-β and IFN-λ1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection. The rescue of UNC-93B- and TLR3deficient cells with the corresponding wild-type allele showed that the genetic defect was the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was rescued further by treatment with exogenous IFN-a or IFN-β (IFN-α/β) but not IFN-λ1. Thus, impaired TLR3- and UNC-93B-dependent IFN-α/β intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3-pathway deficiencies.

Published
2012
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39. Mouse ES and iPS cells can form similar definitive endoderm despite differences in imprinted genes

Author

Christodoulou, Constantina, Longmire, Tyler A., Shen, Steven S., Bourdon, Alice, Sommer, Cesar A., Gadue, Paul, Spira, Avrum, Gouon-Evans, Valerie, Murphy, George J., Mostoslavsky, Gustavo, and Kotton, Darrell N.

Subjects
R and D Systems, Harvard University. Harvard Stem Cell Institute, Analysis, Genes -- Analysis, Software industry -- Analysis, House mouse -- Analysis, Computer software industry -- Analysis, Mice -- Analysis
Abstract

The directed differentiation of iPS and ES cells into definitive endoderm (DE) would allow the derivation of otherwise inaccessible progenitors for endodermal tissues. However, a global comparison of the relative [...]

Published
2011
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42. A mechanosensitive transcriptional mechanism that controls angiogenesis

Author

Mammoto, Akiko, Connor, Kip M., Mammoto, Tadanori, Yung, Chong Wing, Huh, Dongeun, Aderman, Christopher M., Mostoslavsky, Gustavo, Smith, Lois E.H., and Ingber, Donald E.

Subjects
Physiological aspects, Research, Cell receptors -- Physiological aspects -- Research, Neovascularization -- Research -- Physiological aspects, Transcription (Genetics) -- Research -- Physiological aspects, DNA binding proteins -- Physiological aspects -- Research, Genetic transcription -- Research -- Physiological aspects
Abstract

Deregulation of angiogenesis-the growth of blood capillaries--contributes to the development of many diseases, including cancer, arthritis and blindness (1,2). Most US Food and Drug Administration (FDA)-approved angiogenesis inhibitors target the [...], Angiogenesis is controlled by physical interactions between cells and extracellular matrix as well as soluble angiogenic factors, such as VEGF. However, the mechanism by which mechanical signals integrate with other microenvironmental cues to regulate neovascularization remains unknown. Here we show that the Rho inhibitor, p190RhoGAP (also known as GRLF1), controls capillary network formation in vitro in human microvascular endothelial cells and retinal angiogenesis in vivo by modulating the balance of activities between two antagonistic transcription factors, TFII-I (also known as GTF21) and GATA2, that govern gene expression of the VEGF receptor VEGFR2 (also known as KDR). Moreover, this new angiogenesis signalling pathway is sensitive to extracellular matrix elasticity as well as soluble VEGF. This is, to our knowledge, the first known functional cross-antagonism between transcription factors that controls tissue morphogenesis, and that responds to both mechanical and chemical cues.

Published
2009

43. Additional file 8 of A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels

Author

Casalia, Mariana L., Casabona, Juan Cruz, Garc��a, Corina, Cavaliere Candedo, Ver��nica, Quint��, H��ctor Ramiro, Far��as, Mar��a Isabel, Gonzalez, Joaqu��n, Gonzalez Mor��n, Dolores, C��rdoba, Marta, Consalvo, Damian, Mostoslavsky, Gustavo, Urbano, Francisco J., Pasquini, Juana, Murer, Mario Gustavo, Rela, Lorena, Kauffman, Marcelo A., and Pitossi, Fernando J.

Abstract

Additional file 1: Table S8. Primer sequence to detect FGD6 mutation in IPS and derived cell lines.

Published
2021
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44. Additional file 5 of A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels

Author

Casalia, Mariana L., Casabona, Juan Cruz, Garc��a, Corina, Cavaliere Candedo, Ver��nica, Quint��, H��ctor Ramiro, Far��as, Mar��a Isabel, Gonzalez, Joaqu��n, Gonzalez Mor��n, Dolores, C��rdoba, Marta, Consalvo, Damian, Mostoslavsky, Gustavo, Urbano, Francisco J., Pasquini, Juana, Murer, Mario Gustavo, Rela, Lorena, Kauffman, Marcelo A., and Pitossi, Fernando J.

Subjects
ComputingMethodologies_PATTERNRECOGNITION
Abstract

Additional file 1: Table S5. Primary antibody list to label pluripotency markers in IPS lines.

Published
2021
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45. Additional file 3 of A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels

Author

Casalia, Mariana L., Casabona, Juan Cruz, Garc��a, Corina, Cavaliere Candedo, Ver��nica, Quint��, H��ctor Ramiro, Far��as, Mar��a Isabel, Gonzalez, Joaqu��n, Gonzalez Mor��n, Dolores, C��rdoba, Marta, Consalvo, Damian, Mostoslavsky, Gustavo, Urbano, Francisco J., Pasquini, Juana, Murer, Mario Gustavo, Rela, Lorena, Kauffman, Marcelo A., and Pitossi, Fernando J.

Abstract

Additional file 1: Table S3. Primers used to amplify endogenous pluripotency genes.

Published
2021
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46. Additional file 4 of A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels

Author

Casalia, Mariana L., Casabona, Juan Cruz, Garc��a, Corina, Cavaliere Candedo, Ver��nica, Quint��, H��ctor Ramiro, Far��as, Mar��a Isabel, Gonzalez, Joaqu��n, Gonzalez Mor��n, Dolores, C��rdoba, Marta, Consalvo, Damian, Mostoslavsky, Gustavo, Urbano, Francisco J., Pasquini, Juana, Murer, Mario Gustavo, Rela, Lorena, Kauffman, Marcelo A., and Pitossi, Fernando J.

Abstract

Additional file 1: Table S4. Primers list for EB lineage detection.

Published
2021
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47. Additional file 7 of A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels

Author

Casalia, Mariana L., Casabona, Juan Cruz, Garc��a, Corina, Cavaliere Candedo, Ver��nica, Quint��, H��ctor Ramiro, Far��as, Mar��a Isabel, Gonzalez, Joaqu��n, Gonzalez Mor��n, Dolores, C��rdoba, Marta, Consalvo, Damian, Mostoslavsky, Gustavo, Urbano, Francisco J., Pasquini, Juana, Murer, Mario Gustavo, Rela, Lorena, Kauffman, Marcelo A., and Pitossi, Fernando J.

Abstract

Additional file 1: Table S7. Antibody list for EB lineage detection.

Published
2021
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48. Additional file 6 of A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels

Author

Casalia, Mariana L., Casabona, Juan Cruz, Garc��a, Corina, Cavaliere Candedo, Ver��nica, Quint��, H��ctor Ramiro, Far��as, Mar��a Isabel, Gonzalez, Joaqu��n, Gonzalez Mor��n, Dolores, C��rdoba, Marta, Consalvo, Damian, Mostoslavsky, Gustavo, Urbano, Francisco J., Pasquini, Juana, Murer, Mario Gustavo, Rela, Lorena, Kauffman, Marcelo A., and Pitossi, Fernando J.

Abstract

Additional file 1: Table S6. Antibody list to characterize neuroepithelial tissue.

Published
2021
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49. Additional file 2 of A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels

Author

Casalia, Mariana L., Casabona, Juan Cruz, Garc��a, Corina, Cavaliere Candedo, Ver��nica, Quint��, H��ctor Ramiro, Far��as, Mar��a Isabel, Gonzalez, Joaqu��n, Gonzalez Mor��n, Dolores, C��rdoba, Marta, Consalvo, Damian, Mostoslavsky, Gustavo, Urbano, Francisco J., Pasquini, Juana, Murer, Mario Gustavo, Rela, Lorena, Kauffman, Marcelo A., and Pitossi, Fernando J.

Subjects
humanities
Abstract

Additional file 1: Table S2. Primers used to amplify bridge regions between genes found in STEMCCA.

Published
2021
Full Text
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50. Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome

Author

Austin, Karyn M., Gupta, Jr., Mohan L., Coats, Scott A., Tulpule, Asmin, Mostoslavsky, Gustavo, Balazs, Alejandro B., Mulligan, Richard C., Daley, George, Pellman, David, and Shimamura, Akiko

Subjects
Diagnosis, Usage, Complications and side effects, Research, Risk factors, Flow cytometry -- Usage -- Research, Genetic disorders -- Diagnosis -- Complications and side effects -- Research -- Risk factors, Acute myelocytic leukemia -- Risk factors -- Diagnosis -- Research -- Complications and side effects
Abstract

Introduction Shwachman-Diamond syndrome (SDS) is an autosomal recessively inherited disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and an increased risk of acute myeloid leukemia (reviewed in refs. (1), [...], Deficiencies in the SBDS gene result in Shwachman-Diamond syndrome (SDS), an inherited bone marrow failure syndrome associated with leukemia predisposition. SBDS encodes a highly conserved protein previously implicated in ribosome biogenesis. Using human primary bone marrow stromal cells (BMSCs), lymphoblasts, and skin fibroblasts, we show that SBDS stabilized the mitotic spindle to prevent genomic instability. SBDS colocalized with the mitotic spindle in control primary BMSCs, lymphoblasts, and skin fibroblasts and bound to purified microtubules. Recombinant SBDS protein stabilized microtubules in vitro. We observed that primary BMSCs and lymphoblasts from SDS patients exhibited an increased incidence of abnormal mitoses. Similarly, depletion of SBDS by siRNA in human skin fibroblasts resulted in increased mitotic abnormalities and aneuploidy that accumulated over time. Treatment of primary BMSCs and lymphoblasts from SDS patients with nocodazole, a microtubule destabilizing agent, led to increased mitotic arrest and apoptosis, consistent with spindle destabilization. Conversely, SDS patient cells were resistant to taxol, a microtubule stabilizing agent. These findings suggest that spindle instability in SDS contributes to bone marrow failure and leukemogenesis.

Published
2008

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