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761 results on '"Lako, Majlinda"'

2. PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects

Author

Atkinson, Robert, Georgiou, Maria, Yang, Chunbo, Szymanska, Katarzyna, Lahat, Albert, Vasconcelos, Elton J. R., Ji, Yanlong, Moya Molina, Marina, Collin, Joseph, Queen, Rachel, Dorgau, Birthe, Watson, Avril, Kurzawa-Akanbi, Marzena, Laws, Ross, Saxena, Abhijit, Shyan Beh, Chia, Siachisumo, Chileleko, Goertler, Franziska, Karwatka, Magdalena, Davey, Tracey, Inglehearn, Chris F., McKibbin, Martin, Lührmann, Reinhard, Steel, David H., Elliott, David J., Armstrong, Lyle, Urlaub, Henning, Ali, Robin R., Grellscheid, Sushma-Nagaraja, Johnson, Colin A., Mozaffari-Jovin, Sina, and Lako, Majlinda

Published
2024
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5. Retinal cells derived from patients with DRAM2-dependent CORD21 dystrophy exhibit key lysosomal enzyme deficiency and lysosomal content accumulation

Author

Tsikandelova, Rozaliya, Galo, Eldo, Cerniauskas, Edvinas, Hallam, Dean, Georgiou, Maria, Cerna-Chavez, Rodrigo, Atkinson, Robert, Palmowski, Pavel, Burté, Florence, Davies, Tracey, Steel, David H., McKibbin, Martin, Bond, Jacquelyn, Haggarty, Jennifer, Whitfield, Phil, Korolchuk, Viktor, Armstrong, Lyle, Yang, Chunbo, Dorgau, Birthe, Kurzawa-Akanbi, Marzena, and Lako, Majlinda

Published
2024
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8. An introduction to the mathematical modelling of iPSCs

Author

Wadkin, Laura E, Orozco-Fuentes, Sirio, Neganova, Irina, Lako, Majlinda, Parker, Nicholas G, and Shukurov, Anvar

Subjects
Quantitative Biology - Cell Behavior
Abstract

The aim of this chapter is to convey the importance and usefulness of mathematical modelling as a tool to achieve a deeper understanding of stem cell biology. We introduce key mathematical concepts (random walk theory, differential equations and agent-based modelling) which form the basis of current descriptions of induced pluripotent stem cells. We hope to encourage a meaningful dialogue between biologists and mathematicians and highlight the value of such an interdisciplinary approach.

Published
2020

9. OCT4 expression in human embryonic stem cells: spatio-temporal dynamics and fate transitions

Author

Wadkin, Laura E, Orozco-Fuentes, Sirio, Neganova, Irina, Lako, Majlinda, Barrio, R A, Baggaley, A W, Parker, Nicholas G, and Shukurov, Anvar

Subjects
Quantitative Biology - Cell Behavior
Abstract

The improved in-vitro regulation of human embryonic stem cell (hESC) pluripotency and differentiation trajectories is required for their promising clinical applications. The temporal and spatial quantification of the molecular interactions controlling pluripotency is also necessary for the development of successful mathematical and computational models. Here we use time-lapse experimental data of OCT4-mCherry fluorescence intensity to quantify the temporal and spatial dynamics of the pluripotency transcription factor OCT4 in a growing hESC colony in the presence and absence of BMP4. We characterise the internal self-regulation of OCT4 using the Hurst exponent and autocorrelation analysis, quantify the intra-cellular fluctuations and consider the diffusive nature of OCT4 evolution for individual cells and pairs of their descendants. We find that OCT4 abundance in the daughter cells fluctuates sub-diffusively, showing anti-persistent self-regulation. We obtain the stationary probability distributions governing hESC transitions amongst the different cell states and establish the times at which pro-fate cells (which later give rise to pluripotent or differentiated cells) cluster in the colony. By quantifying the similarities between the OCT4 expression amongst neighbouring cells, we show that hESCs express similar OCT4 to cells within their local neighbourhood within the first two days of the experiment and before BMP4 treatment. Our framework allows us to quantify the relevant properties of proliferating hESC colonies and the procedure is widely applicable to other transcription factors and cell populations.

Published
2020

14. Quantification of the morphological characteristics of hESC colonies

Author

Orozco-Fuentes, Sirio, Neganova, Irina, Wadkin, Laura E., Baggaley, Andrew W., Barrio, Rafael A., Lako, Majlinda, Shukurov, Anvar, and Parker, Nicholas G.

Subjects
Quantitative Biology - Quantitative Methods, Quantitative Biology - Cell Behavior
Abstract

The maintenance of the pluripotent state in human embryonic stem cells (hESCs) is critical for further application in regenerative medicine, drug testing and studies of fundamental biology. Currently, the selection of the best quality cells and colonies for propagation is typically performed by eye, in terms of the displayed morphological features, such as prominent/abundant nucleoli and a colony with a tightly packed appearance and a well-defined edge. Using image analysis and computational tools, we precisely quantify these properties using phase-contrast images of hESC colonies of different sizes (0.1 -- 1.1$\, \text{mm}^2$) during days 2, 3 and 4 after plating. Our analyses reveal noticeable differences in their structure influenced directly by the colony area $A$. Large colonies ($A > 0.6 \, \text{mm}^2$) have cells with smaller nuclei and a short intercellular distance when compared with small colonies ($A < 0.2 \, \text{mm}^2$). The gaps between the cells, which are present in small and medium sized colonies with $A \le 0.6 \, \text{mm}^2$, disappear in large colonies ($A > 0.6 \, \text{mm}^2$) due to the proliferation of the cells in the bulk. This increases the colony density and the number of nearest neighbours. We also detect the self-organisation of cells in the colonies where newly divided (smallest) cells cluster together in patches, separated from larger cells at the final stages of the cell cycle. This might influence directly cell-to-cell interactions and the community effects within the colonies since the segregation induced by size differences allows the interchange of neighbours as the cells proliferate and the colony grows. Our findings are relevant to efforts to determine the quality of hESC colonies and establish colony characteristics database.

Published
2019

16. Conjunctival epithelial cells resist productive SARS-CoV-2 infection

Author

Jackson, Robert M., Hatton, Catherine F., Spegarova, Jarmila Stremenova, Georgiou, Maria, Collin, Joseph, Stephenson, Emily, Verdon, Bernard, Haq, Iram J., Hussain, Rafiqul, Coxhead, Jonathan M., Mudhar, Hardeep-Singh, Wagner, Bart, Hasoon, Megan, Davey, Tracey, Rooney, Paul, Khan, C.M. Anjam, Ward, Chris, Brodlie, Malcolm, Haniffa, Muzlifah, Hambleton, Sophie, Armstrong, Lyle, Figueiredo, Francisco, Queen, Rachel, Duncan, Christopher J.A., and Lako, Majlinda

Published
2022
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18. A single cell atlas of human cornea that defines its development, limbal progenitor cells and their interactions with the immune cells

Author

Collin, Joseph, Queen, Rachel, Zerti, Darin, Bojic, Sanja, Dorgau, Birthe, Moyse, Nicky, Molina, Marina Moya, Yang, Chunbo, Dey, Sunanda, Reynolds, Gary, Hussain, Rafiqul, Coxhead, Jonathan M., Lisgo, Steven, Henderson, Deborah, Joseph, Agatha, Rooney, Paul, Ghosh, Saurabh, Clarke, Lucy, Connon, Che, Haniffa, Muzlifah, Figueiredo, Francisco, Armstrong, Lyle, and Lako, Majlinda

Published
2021
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22. Germline TET2 loss of function causes childhood immunodeficiency and lymphoma

Author

Stremenova Spegarova, Jarmila, Lawless, Dylan, Mohamad, Siti Mardhiana Binti, Engelhardt, Karin R., Doody, Gina, Shrimpton, Jennifer, Rensing-Ehl, Anne, Ehl, Stephan, Rieux-Laucat, Frederic, Cargo, Catherine, Griffin, Helen, Mikulasova, Aneta, Acres, Meghan, Morgan, Neil V., Poulter, James A., Sheridan, Eamonn G., Chetcuti, Philip, O'Riordan, Sean, Anwar, Rashida, Carter, Clive R., Przyborski, Stefan, Windebank, Kevin, Cant, Andrew J., Lako, Majlinda, Bacon, Chris M., Savic, Sinisa, and Hambleton, Sophie

Published
2020
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23. Investigating light sensitivity in bipolar disorder (HELIOS-BD)

Author

Roguski, Amber, primary, Needham, Nicole, additional, MacGillivray, Tom, additional, Martinovic, Jasna, additional, Dhillon, Baljean, additional, Riha, Renata L., additional, Armstrong, Lyle, additional, Campbell, Iain, additional, Ferguson, Amy, additional, Hilgen, Gerrit, additional, Lako, Majlinda, additional, Ritter, Philipp, additional, Santhi, Nayantara, additional, von Schantz, Malcolm, additional, Spitschan, Manuel, additional, and Smith, Daniel J., additional

Published
2024
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27. Decellularised extracellular matrix-derived peptides from neural retina and retinal pigment epithelium enhance the expression of synaptic markers and light responsiveness of human pluripotent stem cell derived retinal organoids

Author

Dorgau, Birthe, Felemban, Majed, Hilgen, Gerrit, Kiening, Martin, Zerti, Darin, Hunt, Nicola Claire, Doherty, Mary, Whitfield, Phil, Hallam, Dean, White, Kathryn, Ding, Yuchun, Krasnogor, Natalio, Al-Aama, Jumana, Asfour, Hani Z., Sernagor, Evelyne, and Lako, Majlinda

Published
2019
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28. Reproducibility of Molecular Phenotypes after Long-Term Differentiation to Human iPSC-Derived Neurons: A Multi-Site Omics Study

Author

Volpato, Viola, Smith, James, Sandor, Cynthia, Ried, Janina S., Baud, Anna, Handel, Adam, Newey, Sarah E., Wessely, Frank, Attar, Moustafa, Whiteley, Emma, Chintawar, Satyan, Verheyen, An, Barta, Thomas, Lako, Majlinda, Armstrong, Lyle, Muschet, Caroline, Artati, Anna, Cusulin, Carlo, Christensen, Klaus, Patsch, Christoph, Sharma, Eshita, Nicod, Jerome, Brownjohn, Philip, Stubbs, Victoria, Heywood, Wendy E., Gissen, Paul, De Filippis, Roberta, Janssen, Katharina, Reinhardt, Peter, Adamski, Jerzy, Royaux, Ines, Peeters, Pieter J., Terstappen, Georg C., Graf, Martin, Livesey, Frederick J., Akerman, Colin J., Mills, Kevin, Bowden, Rory, Nicholson, George, Webber, Caleb, Cader, M. Zameel, and Lakics, Viktor

Published
2018
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29. Extracellular matrix component expression in human pluripotent stem cell-derived retinal organoids recapitulates retinogenesis in vivo and reveals an important role for IMPG1 and CD44 in the development of photoreceptors and interphotoreceptor matrix

Author

Felemban, Majed, Dorgau, Birthe, Hunt, Nicola Claire, Hallam, Dean, Zerti, Darin, Bauer, Roman, Ding, Yuchun, Collin, Joseph, Steel, David, Krasnogor, Natalio, Al-Aama, Jumana, Lindsay, Susan, Mellough, Carla, and Lako, Majlinda

Published
2018
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34. Deciphering the spatio-temporal transcriptional and chromatin accessibility of human retinal organoid development at the single cell level

Author

Dorgau, Birthe, primary, Collin, Joseph, additional, Rozanska, Agata, additional, Boczonadi, Veronika, additional, MoyaMolina, Marina, additional, Hussain, Rafiqul, additional, Coxhead, Jonathan, additional, Dhanaseelan, Tamilvendhan, additional, Armstrong, Lyle, additional, Queen, Rachel, additional, and Lako, Majlinda, additional

Published
2023
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37. Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency

Author

Muñoz-López, Alvaro, Romero-Moya, Damià, Prieto, Cristina, Ramos-Mejía, Verónica, Agraz-Doblas, Antonio, Varela, Ignacio, Buschbeck, Marcus, Palau, Anna, Carvajal-Vergara, Xonia, Giorgetti, Alessandra, Ford, Anthony, Lako, Majlinda, Granada, Isabel, Ruiz-Xivillé, Neus, Rodríguez-Perales, Sandra, Torres-Ruíz, Raul, Stam, Ronald W., Fuster, Jose Luis, Fraga, Mario F., Nakanishi, Mahito, Cazzaniga, Gianni, Bardini, Michela, Cobo, Isabel, Bayon, Gustavo F., Fernandez, Agustin F., Bueno, Clara, and Menendez, Pablo

Published
2016
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41. Incorporating microglia‐like cells in human induced pluripotent stem cell‐derived retinal organoids

Author

Chichagova, Valeria, primary, Georgiou, Maria, additional, Carter, Madeleine, additional, Dorgau, Birthe, additional, Hilgen, Gerrit, additional, Collin, Joseph, additional, Queen, Rachel, additional, Chung, Git, additional, Ajeian, Jila, additional, Moya‐Molina, Marina, additional, Kustermann, Stefan, additional, Pognan, Francois, additional, Hewitt, Philip, additional, Schmitt, Michael, additional, Sernagor, Evelyne, additional, Armstrong, Lyle, additional, and Lako, Majlinda, additional

Published
2023
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42. Single cell RNA sequencing reveals transcriptional changes of human choroidal and retinal pigment epithelium cells during fetal development, in healthy adult and intermediate age-related macular degeneration

Author

Collin, Joseph, primary, Hasoon, Megan S R, additional, Zerti, Darin, additional, Hammadi, Sarah, additional, Dorgau, Birthe, additional, Clarke, Lucy, additional, Steel, David, additional, Hussain, Rafiqul, additional, Coxhead, Jonathan, additional, Lisgo, Steven, additional, Queen, Rachel, additional, and Lako, Majlinda, additional

Published
2023
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44. Retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina

Author

Kurzawa‐Akanbi, Marzena, primary, Whitfield, Phillip, additional, Burté, Florence, additional, Bertelli, Pietro Maria, additional, Pathak, Varun, additional, Doherty, Mary, additional, Hilgen, Birthe, additional, Gliaudelytė, Lina, additional, Platt, Mark, additional, Queen, Rachel, additional, Coxhead, Jonathan, additional, Porter, Andrew, additional, Öberg, Maria, additional, Fabrikova, Daniela, additional, Davey, Tracey, additional, Beh, Chia Shyan, additional, Georgiou, Maria, additional, Collin, Joseph, additional, Boczonadi, Veronika, additional, Härtlova, Anetta, additional, Taggart, Michael, additional, Al‐Aama, Jumana, additional, Korolchuk, Viktor I, additional, Morris, Christopher M, additional, Guduric‐Fuchs, Jasenka, additional, Steel, David H, additional, Medina, Reinhold J, additional, Armstrong, Lyle, additional, and Lako, Majlinda, additional

Published
2022
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47. Retinal organoids provide unique insights into molecular signatures of inherited retinal disease throughout retinogenesis.

Author

Watson, Avril and Lako, Majlinda

Subjects
*RETINAL diseases, *GENETIC disorders, *INDUCED pluripotent stem cells, *RETINITIS pigmentosa, *ORGANOIDS
Abstract

The demand for induced pluripotent stem cells (iPSC)‐derived retinal organoid and retinal pigment epithelium (RPE) models for the modelling of inherited retinopathies has increased significantly in the last decade. These models are comparable with foetal retinas up until the later stages of retinogenesis, expressing all of the key neuronal markers necessary for retinal function. These models have proven to be invaluable in the understanding of retinogenesis, particular in the context of patient‐specific diseases. Inherited retinopathies are infamously described as clinically and phenotypically heterogeneous, such that developing gene/mutation‐specific animal models in each instance of retinal disease is not financially or ethically feasible. Further to this, many animal models are insufficient in the study of disease pathogenesis due to anatomical differences and failure to recapitulate human disease phenotypes. In contrast, iPSC‐derived retinal models provide a high throughput platform which is physiologically relevant for studying human health and disease. They also serve as a platform for drug screening, gene therapy approaches and in vitro toxicology of novel therapeutics in pre‐clinical studies. One unique characteristic of stem cell‐derived retinal models is the ability to mimic in vivo retinogenesis, providing unparalleled insights into the effects of pathogenic mutations in cells of the developing retina, in a highly accessible way. This review aims to give the reader an overview of iPSC‐derived retinal organoids and/or RPE in the context of disease modelling of several inherited retinopathies including Retinitis Pigmentosa, Stargardt disease and Retinoblastoma. We describe the ability of each model to recapitulate in vivo disease phenotypes, validate previous findings from animal models and identify novel pathomechanisms that underpin individual IRDs. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa

Author

Buskin, Adriana, Zhu, Lili, Chichagova, Valeria, Basu, Basudha, Mozaffari-Jovin, Sina, Dolan, David, Droop, Alastair, Collin, Joseph, Bronstein, Revital, Mehrotra, Sudeep, Farkas, Michael, Hilgen, Gerrit, White, Kathryn, Pan, Kuan-Ting, Treumann, Achim, Hallam, Dean, Bialas, Katarzyna, Chung, Git, Mellough, Carla, Ding, Yuchun, Krasnogor, Natalio, Przyborski, Stefan, Zwolinski, Simon, Al-Aama, Jumana, Alharthi, Sameer, Xu, Yaobo, Wheway, Gabrielle, Szymanska, Katarzyna, McKibbin, Martin, Inglehearn, Chris F., Elliott, David J., Lindsay, Susan, Ali, Robin R., Steel, David H., Armstrong, Lyle, Sernagor, Evelyne, Urlaub, Henning, Pierce, Eric, Lührmann, Reinhard, Grellscheid, Sushma-Nagaraja, Johnson, Colin A., and Lako, Majlinda

Published
2018
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