Embryonic hematopoiesis in vertebrate somites gives rise to definitive hematopoietic stem cells

J Mol Cell Biol. 2016 Aug;8(4):288-301. doi: 10.1093/jmcb/mjw024. Epub 2016 Jun 1.


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.

Keywords: blood; definitive hematopoiesis; embryos; primitive hematopoiesis; somite; stem cells; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Animals, Genetically Modified
  • Blood Cells / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / radiation effects
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / radiation effects
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / radiation effects
  • Green Fluorescent Proteins / metabolism
  • Hematopoiesis* / radiation effects
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / radiation effects
  • Light
  • Mesoderm / cytology
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / radiation effects
  • Somites / cytology*
  • Somites / embryology*
  • Somites / radiation effects
  • Zebrafish / embryology*
  • Zebrafish / genetics


  • Green Fluorescent Proteins