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Human induced pluripotent stem cell-derived macrophages share ontogeny with MYB-independent tissue-resident macrophages

ABSTRACT: Tissue-resident macrophages such as microglia, Kupffer 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 knock-outs 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 knock-out strategy we show that human iPSC-derived monocytes/macrophages develop in a 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 and Langerhans cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE93285 | GEO | 2017/01/07

SECONDARY ACCESSION(S): PRJNA360466

REPOSITORIES: GEO

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