Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors


Franziska Paul, Ya'ara Arkin, Amir Giladi, Diego Adhemar Jaitin, Ephraim Kenigsberg, Hadas Keren-Shaul, Deborah Winter, David Lara-Astiaso, Meital Gury, Assaf Weiner, Eyal David, Nadav Cohen, Felicia Kathrine Bratt Lauridsen, Simon Haas, Andreas Schlitzer, Alexander Mildner, Florent Ginhoux, Steffen Jung, Andreas Trumpp, Bo Torben Porse, Amos Tanay, Ido Amit


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.