Large-scale transcriptional profiling and functional assays reveal important roles for Rho-GTPase signalling and SCL during haematopoietic differentiation of human embryonic stem cells

• DOI: 10.1093/hmg/ddr431
• Publication Date: 2011-09-22T02:18:08Z
• Authors: Sun Yung; Maria Ledran; Inmaculada Moreno...; Ana Conesa; David Montaner; Joaquín Dopazo; Ian Dimmick; Nicholas J. Slater; Lamin Marenah; Pedro J. Real; Iliana Paraskevop...; Viviana Bisbal; Deborah Burks; Mauro Santibanez-...; Ruben Moreno; Joanne Mountford; Pablo Menendez; Lyle Armstrong; Majlinda Lako
• Keywords: 0301 basic medicine; Anemia, Hemolytic; Cell Line; Mice; 03 medical and health sciences; Erythroid Cells; Proto-Oncogene Proteins; HOXB4 EXPRESSION; Paracrine Communication; Basic Helix-Loop-Helix Transcription Factors; Animals; Cluster Analysis; Humans; Cell Lineage; Myeloid Cells; MACROPHAGES; Embryonic Stem Cells; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; LINEAGES; Cell Differentiation; IN-VITRO; Flow Cytometry; Hematopoietic Stem Cells; SCL/TAL1; PROGENITOR CELLS; ENDOTHELIUM; Acute Disease; ERYTHROPOIESIS; RAC1; GENERATION; Signal Transduction

Understanding the transcriptional cues that direct differentiation of human embryonic stem cells (hESCs) and human-induced pluripotent to defined functional cell types is essential for future clinical applications. In this study, we have compared profiles haematopoietic progenitors derived from hESCs at various developmental stages a feeder- serum-free method show largest changes occur during first 4 days differentiation. Data mining on basis molecular function revealed Rho-GTPase signalling as key regulator Inhibition pathway resulted in significant reduction numbers emerging throughout window, thereby uncovering previously unappreciated role development. Our analysis indicated SCL was 11th most upregulated transcript hESC process. Overexpression promoted meso-endodermal lineages, emergence erythro-megakaryocytic accelerated erythroid Importantly, intrasplenic transplantation SCL-overexpressing hESC-derived enhanced recovery induced acute anaemia without engraftment, suggesting paracrine-mediated effect.