Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros
| Autor: | Vincenzo Calvanese, Magdaline Costa, Aude Conscience, Vanta J. Jokubaitis, Claire E Hirst, Katerina Vlahos, Alicia Oshlack, Belinda Phipson, Freya Bruveris, Brenda Williams, Hanna K. A. Mikkola, Simone Liebscher, Andrew G. Elefanty, Qing C Yu, Elizabeth Ng, Edouard G. Stanley, Vania Januar, Katja Schenke-Layland, Zhen Zhang, Richard Saffery, Susan K. Nilsson, David A. Elliott, Lisa Azzola, Jennifer Durnall, Steven Anthony Jackson, Jovana Maksimovic, David N. Haylock |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cellular differentiation Biomedical Engineering CD34 Bioengineering Embryoid body Biology Applied Microbiology and Biotechnology Embryonic stem cell Cell biology Endothelial stem cell 03 medical and health sciences 030104 developmental biology Cord blood embryonic structures Molecular Medicine Stem cell Biotechnology Adult stem cell |
| Zdroj: | Nature Biotechnology. 34:1168-1179 |
| ISSN: | 1546-1696 1087-0156 |
| DOI: | 10.1038/nbt.3702 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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