期刊
STEM CELL REPORTS
卷 8, 期 2, 页码 334-345出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2016.12.020
关键词
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资金
- RCUK-Medical Research Council
- Heatley Merck Sharpe and Dohme studentship
- Oxford Martin School [LC0910-004]
- Wellcome Trust [WTISSF121302, 090532/Z/09/Z]
- Monument Trust Discovery Award from Parkinson's UK [2581970, SC037554]
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford
- NIHR Comprehensive Local Research Network
- Medical Research Council [1238223] Funding Source: researchfish
Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knockouts and lineage tracing, but their applicability to human development has not been formally demonstrated. Here, we use human induced pluripotent stem cells (iPSCs) as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knockout strategy, we show that human iPSC-derived monocytes/ macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU. 1)-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells.
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