title: Enforced expression of Hoxa5 in haematopoietic stem cells leads to aberrant erythropoiesis in vivo.
abstract: Hoxa5 is preferentially expressed in haematopoietic stem cells (HSCs) and multipotent progenitor cells (MPPs), and is more highly expressed in expanding HSCs. To date, little is known regarding the role of Hoxa5 in HSCs and downstream progenitor cells in vivo. In this study, we show that increased expression of Hoxa5 in haematopoietic stem cells leads to aberrant erythropoiesis in vivo. Hoxa5 differentially modifies the cell cycle of HSCs and lineage committed progenitor cells, depending on the cellular context. Hoxa5 drives HSCs, but not MPPs, through the cell cycle and arrests erythroid progenitor cells in G0 phase. Although the HSC pool shrinks after overexpression of Hoxa5, HSCs sustain the abilities of self-renewal and multipotency. In vivo, Hoxa5 has two effects on erythropoiesis: it causes a predominance of mature erythroid lineage cells and the partial apoptosis of erythroid progenitors. RNA-seq indicates that multiple biological processes, including erythrocyte homeostasis, cell metabolism, and apoptosis, are modified by Hoxa5. The results of this study indicate that Hoxa5 is a key regulator of the HSC cell cycle, and the inappropriate expression of Hoxa5 in lineage-committed progenitor cells leads to aberrant erythropoiesis.
authors.affiliation: a Department of Hematology ; Third Affiliated Hospital of Sun Yat-Sen University ; Guangzhou , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Xiangzhong
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Dong
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Liu
authors.forename: Tongjie
authors.initials: T
authors.lastname: Wang
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Geng
authors.forename: Shumin
authors.initials: S
authors.lastname: Fang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
authors.forename: Jiekai
authors.initials: J
authors.lastname: Chen
authors.forename: Guangjin
authors.initials: G
authors.lastname: Pan
authors.forename: Jinyong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology*; D019295:Computational Biology; D004920:Erythropoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D014157:Transcription Factors
chemical_list: D018398:Homeodomain Proteins; C059637:Hoxa5 protein, mouse; D010750:Phosphoproteins; D014157:Transcription Factors
keywords: BFU-E, burst-forming unit-erythroid; CFU-G, colony forming unit-granulocyte; CFU-GM, colony forming unit-granulocyte macrophage; CMP, common myeloid progenitor; GMP, granulocyte monocyte progenitor; HSC, haematopoietic stem cell; LSK, lineage negative, Sca1 positive, cKit positive; MEP, megakaryocyte-erythroid progenitor; MP, myeloid progenitor; MPP, multipotent progenitor; apoptosis; cell cycle; erythropoiesis; haematopoietic stem cells, Hoxa5