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Nucleic Acids Res. 2016 Dec 20. pii: gkw1214. doi: 10.1093/nar/gkw1214. [Epub ahead of print]

Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors.

Author information

1
Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA.
2
Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
3
Department of Neurobiology, Yale School of Medicine, New Haven, CT 06520, USA.
4
Epidemiology Program, University of Hawaii Cancer Center, HI 96813, USA.
5
Hematology, Yale Comprehensive Cancer Center and Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
6
JiangXi Key Laboratory of Systems Biomedicine, Jiujiang University, Jiangxi 332000, PR China.
7
Department of Genetics, Stanford University, Palo, Alto, CA 94305, USA.
8
Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
9
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Guangdong Key Laboratory of Biochip Technology, Southern Medical University, Guangzhou 510515, Guangdong, PR China Xinghua.Pan@Yale.edu.
10
Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA Sherman.weissman@yale.edu.

Abstract

Molecular changes underlying stem cell differentiation are of fundamental interest. scRNA-seq on murine hematopoietic stem cells (HSC) and their progeny MPP1 separated the cells into 3 main clusters with distinct features: active, quiescent, and an un-characterized cluster. Induction of anemia resulted in mobilization of the quiescent to the active cluster and of the early to later stage of cell cycle, with marked increase in expression of certain transcription factors (TFs) while maintaining expression of interferon response genes. Cells with surface markers of long term HSC increased the expression of a group of TFs expressed highly in normal cycling MPP1 cells. However, at least Id1 and Hes1 were significantly activated in both HSC and MPP1 cells in anemic mice. Lineage-specific genes were differently expressed between cells, and correlated with the cell cycle stages with a specific augmentation of erythroid related genes in the G2/M phase. Most lineage specific TFs were stochastically expressed in the early precursor cells, but a few, such as Klf1, were detected only at very low levels in few precursor cells. The activation of these factors may correlate with stages of differentiation. This study reveals effects of cell cycle progression on the expression of lineage specific genes in precursor cells, and suggests that hematopoietic stress changes the balance of renewal and differentiation in these homeostatic cells.

PMID:
28003475
DOI:
10.1093/nar/gkw1214
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