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
Affiliations
Kathleen E. McGrath
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA
Jenna M. Frame
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA
Katherine H. Fegan
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA
James R. Bowen
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA
Simon J. Conway
Developmental Biology and Neonatal Medicine Program, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Seana C. Catherman
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA
Paul D. Kingsley
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA
Anne D. Koniski
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA
James Palis
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA
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.
