Abstract

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 subpopulations 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.

Dataset information:

Genomic assay	scRNA-seq	Samples	Neutrophils, monocytes, DCs, basophils, eosinophils, erythroid and lymphoid progenitors
Method for deriving gene sets	EM-based clustering	Number of gene sets	19
Figure source	Figure 1	Data source	Table S3

Associated gene sets:

Gene set #	Description	No. of genes
1	Erythroid progenitors	286
2	Erythroid progenitors	141
3	Erythroid progenitors	93
4	Erythroid progenitors	33
5	Erythroid progenitors	121
6	Erythroid progenitors	68
7	Erythroid progenitors	129
8	Erythroid progenitors	198
9	Neutrophil	131
10	Monocyte	44
11	DC	285
12	Basophil	55
13	Basophil	230
14	Monocyte	53
15	Monocyte	39
16	Neutrophil	56
17	Neutrophil	130
18	Eosinophil	636
19	Lymphoid	302

A total of 3030 genes are associated with this dataset.