Lookup NU author(s): Ian Dimmick,
Dr Nicholas Slater,
Professor Lyle Armstrong,
Professor Majlinda Lako
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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.
Author(s): Yung S, Ledran M, Moreno-Gimeno I, Conesa A, Montaner D, Dopazo J, Dimmick I, Slater NJ, Marenah L, Real PJ, Paraskevopoulou I, Bisbal V, Burks D, Santibanez-Koref M, Moreno R, Mountford J, Menendez P, Armstrong L, Lako M
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Print publication date: 21/09/2011
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
PubMed id: 21937587
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