期刊
CELL
卷 163, 期 7, 页码 1663-1677出版社
CELL PRESS
DOI: 10.1016/j.cell.2015.11.013
关键词
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资金
- European Research Council
- I-CORE for chromatin and RNA regulation
- Israel Science foundation [782/11, 1050/12]
- BLUEPRINT FP7 consortium
- Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine
- Minerva Stiftung research grant
- National Human Genome Research Institute Center for Excellence in Genome Science [1P50HG006193]
- NovoNordisk Foundation (The Novo Nordisk Foundation section for Stem Cell Biology in Human Disease)
- Lundbeck Foundation [R108-2012-10312] Funding Source: researchfish
Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory mechanisms. Here, we comprehensively map myeloid progenitor sub-populations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting that the process is tightly regulated. Histone maps and knockout assays are consistent with early transcriptional priming, while traditional transplantation experiments suggest that in vivo priming may still allow for plasticity given strong perturbations. These data establish a reference model and general framework for studying hematopoiesis at single-cell resolution.
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