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Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros.
Ng, Elizabeth S; Azzola, Lisa; Bruveris, Freya F; Calvanese, Vincenzo; Phipson, Belinda; Vlahos, Katerina; Hirst, Claire; Jokubaitis, Vanta J; Yu, Qing C; Maksimovic, Jovana; Liebscher, Simone; Januar, Vania; Zhang, Zhen; Williams, Brenda; Conscience, Aude; Durnall, Jennifer; Jackson, Steven; Costa, Magdaline; Elliott, David; Haylock, David N; Nilsson, Susan K; Saffery, Richard; Schenke-Layland, Katja; Oshlack, Alicia; Mikkola, Hanna K A; Stanley, Edouard G; Elefanty, Andrew G.
Afiliación
  • Ng ES; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Azzola L; Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
  • Bruveris FF; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Calvanese V; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Phipson B; Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
  • Vlahos K; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, USA.
  • Hirst C; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, California, USA.
  • Jokubaitis VJ; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Yu QC; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Maksimovic J; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
  • Liebscher S; Department of Anatomy and Neuroscience, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia.
  • Januar V; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Shanghai, P.R. China.
  • Zhang Z; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Williams B; Department of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany.
  • Conscience A; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Durnall J; Commonwealth Scientific and Industrial Research Organisation (CSIRO), Manufacturing, Clayton, Victoria, Australia.
  • Jackson S; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
  • Costa M; Commonwealth Scientific and Industrial Research Organisation (CSIRO), Manufacturing, Clayton, Victoria, Australia.
  • Elliott D; Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
  • Haylock DN; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Nilsson SK; Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Saffery R; Australian Centre for Blood Diseases, Monash University, Alfred Medical Research Precinct, Melbourne, Victoria, Australia.
  • Schenke-Layland K; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Oshlack A; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
  • Mikkola HK; Commonwealth Scientific and Industrial Research Organisation (CSIRO), Manufacturing, Clayton, Victoria, Australia.
  • Stanley EG; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
  • Elefanty AG; Commonwealth Scientific and Industrial Research Organisation (CSIRO), Manufacturing, Clayton, Victoria, Australia.
Nat Biotechnol ; 34(11): 1168-1179, 2016 Nov.
Article en En | MEDLINE | ID: mdl-27748754
The ability to generate hematopoietic stem cells from human pluripotent cells would enable many biomedical applications. We find that hematopoietic CD34+ cells in spin embryoid bodies derived from human embryonic stem cells (hESCs) lack HOXA expression compared with repopulation-competent human cord blood CD34+ cells, indicating incorrect mesoderm patterning. Using reporter hESC lines to track the endothelial (SOX17) to hematopoietic (RUNX1C) transition that occurs in development, we show that simultaneous modulation of WNT and ACTIVIN signaling yields CD34+ hematopoietic cells with HOXA expression that more closely resembles that of cord blood. The cultures generate a network of aorta-like SOX17+ vessels from which RUNX1C+ blood cells emerge, similar to hematopoiesis in the aorta-gonad-mesonephros (AGM). Nascent CD34+ hematopoietic cells and corresponding cells sorted from human AGM show similar expression of cell surface receptors, signaling molecules and transcription factors. Our findings provide an approach to mimic in vitro a key early stage in human hematopoiesis for the generation of AGM-derived hematopoietic lineages from hESCs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Proteínas de Homeodominio / Neovascularización Fisiológica / Células Madre Embrionarias / Mesonefro Límite: Humans Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Proteínas de Homeodominio / Neovascularización Fisiológica / Células Madre Embrionarias / Mesonefro Límite: Humans Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos