Large-scale transcriptional profiling and functional assays reveal important roles for Rho-GTPase signalling and SCL during haematopoietic differentiation of human embryonic stem cells
| العنوان: | Large-scale transcriptional profiling and functional assays reveal important roles for Rho-GTPase signalling and SCL during haematopoietic differentiation of human embryonic stem cells |
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| المؤلفون: | Viviana Bisbal, Pedro J. Real, Sun Yung, Lyle Armstrong, Rubén Moreno, Joaquín Dopazo, David Montaner, Deborah J. Burks, Majlinda Lako, Ana Conesa, Lamin Marenah, Iliana Paraskevopoulou, Mauro Santibanez-Koref, Joanne C. Mountford, Maria H. Ledran, Ian Dimmick, Nicholas J. Slater, Pablo Menendez, Inmaculada Moreno-Gimeno |
| المصدر: | Human Molecular Genetics. 20:4932-4946 |
| بيانات النشر: | Oxford University Press (OUP), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | rho GTP-Binding Proteins, Anemia, Hemolytic, Cell type, Biology, Cell Line, Mice, Erythroid Cells, Proto-Oncogene Proteins, Paracrine Communication, Basic Helix-Loop-Helix Transcription Factors, Genetics, Animals, Cluster Analysis, Humans, Cell Lineage, Myeloid Cells, Progenitor cell, Induced pluripotent stem cell, Molecular Biology, Embryonic Stem Cells, T-Cell Acute Lymphocytic Leukemia Protein 1, Genetics (clinical), Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Cell Differentiation, General Medicine, Flow Cytometry, Hematopoietic Stem Cells, Embryonic stem cell, Cell biology, Gene expression profiling, Transplantation, Haematopoiesis, Cell culture, Acute Disease, embryonic structures, Transcriptome, Signal Transduction, Stem Cell Transplantation |
| الوصف: | Understanding the transcriptional cues that direct differentiation of human embryonic stem cells (hESCs) and human-induced pluripotent stem cells to defined and functional cell types is essential for future clinical applications. In this study, we have compared transcriptional profiles of haematopoietic progenitors derived from hESCs at various developmental stages of a feeder- and serum-free differentiation method and show that the largest transcriptional changes occur during the first 4 days of differentiation. Data mining on the basis of molecular function revealed Rho-GTPase signalling as a key regulator of differentiation. Inhibition of this pathway resulted in a significant reduction in the numbers of emerging haematopoietic progenitors throughout the differentiation window, thereby uncovering a previously unappreciated role for Rho-GTPase signalling during human haematopoietic development. Our analysis indicated that SCL was the 11th most upregulated transcript during the first 4 days of the hESC differentiation process. Overexpression of SCL in hESCs promoted differentiation to meso-endodermal lineages, the emergence of haematopoietic and erythro-megakaryocytic progenitors and accelerated erythroid differentiation. Importantly, intrasplenic transplantation of SCL-overexpressing hESC-derived haematopoietic cells enhanced recovery from induced acute anaemia without significant cell engraftment, suggesting a paracrine-mediated effect. |
| تدمد: | 1460-2083 0964-6906 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1a96aead7ea02948a18a6d1514901b44 https://doi.org/10.1093/hmg/ddr431 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1a96aead7ea02948a18a6d1514901b44 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602083 09646906 |
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