title: Embryonic hematopoiesis in vertebrate somites gives rise to definitive hematopoietic stem cells.
abstract: Hematopoietic stem cells (HSCs) replenish all types of blood cells. It is debating whether HSCs in adults solely originate from the aorta-gonad-mesonephros (AGM) region, more specifically, the dorsal aorta, during embryogenesis. Here, we report that somite hematopoiesis, a previously unwitnessed hematopoiesis, can generate definitive HSCs (dHSCs) in zebrafish. By transgenic lineage tracing, we found that a subset of cells within the forming somites emigrate ventromedially and mix with lateral plate mesoderm-derived primitive hematopoietic cells before the blood circulation starts. These somite-derived hematopoietic precursors and stem cells (sHPSCs) subsequently enter the circulation and colonize the kidney of larvae and adults. RNA-seq analysis reveals that sHPSCs express hematopoietic genes with sustained expression of many muscle/skeletal genes. Embryonic sHPSCs transplanted into wild-type embryos expand during growth and survive for life time with differentiation into various hematopoietic lineages, indicating self-renewal and multipotency features. Therefore, the embryonic origin of dHSCs in adults is not restricted to the AGM.
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China mengam@mail.tsinghua.edu.cn jhqiu2008@126.com.
authors.forename: Juhui
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, and Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing 100871, China Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China Center for Molecular and Translational Medicine, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yixia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Biological Sciences, China Agricultural University, Beijing 100083, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shenghong
authors.initials: S
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, and Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing 100871, China Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China Center for Molecular and Translational Medicine, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Fuchou
authors.initials: F
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China mengam@mail.tsinghua.edu.cn jhqiu2008@126.com.
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
mesh_terms: D000375:Aging; D000818:Animals; D030801:Animals, Genetically Modified; D001773:Blood Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000528:radiation effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000528:radiation effects; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006410:Hematopoiesis / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D008027:Light; D008648:Mesoderm / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000528:radiation effects; D019170:Somites / Q000166:cytology* / Q000196:embryology* / Q000528:radiation effects; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
chemical_list: D049452:Green Fluorescent Proteins
keywords: blood; definitive hematopoiesis; embryos; primitive hematopoiesis; somite; stem cells; zebrafish