Distinct Sources of Hematopoietic Progenitors Emerge before HSCs and Provide Functional Blood Cells in the Mammalian Embryo

Kathleen E. McGrath, Jenna M. Frame, Katherine H. Fegan, James R. Bowen, Simon J. Conway, Seana C. Catherman, Paul D. Kingsley, Anne D. Koniski, James Palis

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Hematopoietic potential arises in mammalian embryos before adult-repopulating hematopoietic stem cells (HSCs). At embryonic day 9.5 (E9.5), we show the first murine definitive erythro-myeloid progenitors (EMPs) have an immunophenotype distinct from primitive hematopoietic progenitors, maturing megakaryocytes and macrophages, and rare B cell potential. EMPs emerge in the yolk sac with erythroid and broad myeloid, but not lymphoid, potential. EMPs migrate to the fetal liver and rapidly differentiate, including production of circulating neutrophils by E11.5. Although the surface markers, transcription factors, and lineage potential associated with EMPs overlap with those found in adult definitive hematopoiesis, they are present in unique combinations or proportions that result in a specialized definitive embryonic progenitor. Furthermore, we find that embryonic stem cell (ESC)-derived hematopoiesis recapitulates early yolk sac hematopoiesis, including primitive, EMP, and rare B cell potential. EMPs do not have long-term potential when transplanted in immunocompromised adults, but they can provide transient adult-like RBC reconstitution. Yolk-sac-derived definitive erythro-myeloid progenitors (EMPs) can be prospectively identified and distinguished from HSC-independent primitive and B cell hematopoietic emergence. Embryonic stem cell maturation produces yolk-sac-like HSC-independent hematopoietic potential. EMPs colonize and differentiate in the early fetal liver, including granulopoiesis. In adults, EMPs can provide transient adult-like RBC reconstitution.

Original languageEnglish (US)
Pages (from-to)1892-1904
Number of pages13
JournalCell Reports
Volume11
Issue number12
DOIs
StatePublished - Jun 30 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    McGrath, K. E., Frame, J. M., Fegan, K. H., Bowen, J. R., Conway, S. J., Catherman, S. C., Kingsley, P. D., Koniski, A. D., & Palis, J. (2015). Distinct Sources of Hematopoietic Progenitors Emerge before HSCs and Provide Functional Blood Cells in the Mammalian Embryo. Cell Reports, 11(12), 1892-1904. https://doi.org/10.1016/j.celrep.2015.05.036