title: Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors.
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.
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yang
authors.affiliation: Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Montrell
authors.initials: M
authors.lastname: Seay
authors.affiliation: Department of Neurobiology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Jin
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, HI, USA.
authors.forename: Lana Xia
authors.initials: LX
authors.lastname: Garmire
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, HI, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Hematology, Yale Comprehensive Cancer Center and Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT, USA.|JiangXi Key Laboratory of Systems Biomedicine, Jiujiang University, Jiangxi, PR China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Genetics, Stanford University, Palo, Alto, CA, USA.
authors.forename: Ghia
authors.initials: G
authors.lastname: Euskirchen
authors.affiliation: Hematology, Yale Comprehensive Cancer Center and Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Halene
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Kluger
authors.affiliation: Department of Genetics, Stanford University, Palo, Alto, CA, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Snyder
authors.affiliation: Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT, USA.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Guangdong Key Laboratory of Biochip Technology, Southern Medical University, Guangzhou, Guangdong, PR China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Sherman Morton
authors.initials: SM
authors.lastname: Weissman
mesh_terms: D000740:Anemia / Q000235:genetics; D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D004920:Erythropoiesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D017423:Sequence Analysis, RNA / Q000379:methods; D059010:Single-Cell Analysis / Q000379:methods*; D000072056:Transcription Factor HES-1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C489734:Hes1 protein, mouse; D000072056:Transcription Factor HES-1; D014157:Transcription Factors