Identification of multipotent progenitors that emerge prior to hematopoietic stem cells in embryonic development

Stem Cell Reports. 2014 Mar 20;2(4):457-72. doi: 10.1016/j.stemcr.2014.02.001. eCollection 2014 Apr 8.


Hematopoiesis in the embryo proceeds in a series of waves, with primitive erythroid-biased waves succeeded by definitive waves, within which the properties of hematopoietic stem cells (multilineage potential, self-renewal, and engraftability) gradually arise. Whereas self-renewal and engraftability have previously been examined in the embryo, multipotency has not been thoroughly addressed, especially at the single-cell level or within well-defined populations. To identify when and where clonal multilineage potential arises during embryogenesis, we developed a single-cell multipotency assay. We find that, during the initiation of definitive hematopoiesis in the embryo, a defined population of multipotent, engraftable progenitors emerges that is much more abundant within the yolk sac (YS) than the aorta-gonad-mesonephros (AGM) or fetal liver. These experiments indicate that multipotent cells appear in concert within both the YS and AGM and strongly implicate YS-derived progenitors as contributors to definitive hematopoiesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / metabolism
  • CD11a Antigen / genetics
  • Cell Differentiation
  • Cell Lineage
  • Colony-Forming Units Assay
  • Embryonic Development* / genetics
  • Female
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Immunophenotyping
  • Leukosialin / genetics
  • Leukosialin / metabolism
  • Mice
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • Phenotype
  • Proto-Oncogene Proteins c-kit / metabolism
  • Yolk Sac / embryology


  • Antigens, Surface
  • CD11a Antigen
  • Leukosialin
  • Proto-Oncogene Proteins c-kit