Functional B-1 progenitor cells are present in the hematopoietic stem cell-deficient embryo and depend on Cbfβ for their development

Michihiro Kobayashi, W. Christopher Shelley, Wooseok Seo, Sasidhar Vemula, Yang Lin, Yan Liu, Reuben Kapur, Ichiro Taniuchi, Momoko Yoshimoto

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

The fetal liver is a major hematopoietic site containing progenitor cells that give rise to nearly all blood cells, including B-1 cells. Because the fetal liver is not a de novo site of hematopoietic stem cell (HSC) or progenitor-cell emergence, it must be seeded by yolk sac (YS)-derived erythromyeloid progenitors at embryonic day (E) 8.5-E10 and aorta-gonado-mesonephros (AGM)-derived HSCs at E10.5-E11.5. Although the B-1 progenitor cell pool in the fetal liver is considered to be of HSC origin, we have previously proposed that YS-derived B-1 progenitors may also contribute to this pool. Until now, it has been impossible to determine whether HSC-independent B-1 progenitor cells exist in the fetal liver. Here, we demonstrate the presence of transplantable fetal-liver B-1 and marginal zone B progenitor cells in genetically engineered HSC-deficient embryos. HSC-deficient YS and AGM tissues produce B-1 progenitors in vitro and thus may serve as sites of origin for the B-1 progenitors that seed the fetal liver. Furthermore, we have found that core-binding factor beta (Cbfβ) expression is required for fetal-liver B-1 progenitor cell maturation and expansion. Our data provide, to our knowledge, the first evidence for the presence of B-1 progenitor cells in the fetal liver that arise independently of HSCs and implicate Cbfβ as a critical molecule in the development of this lineage.

Original languageEnglish (US)
Pages (from-to)12151-12156
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number33
DOIs
StatePublished - Aug 19 2014

Keywords

  • Hemogenic endothelial cell
  • Immune layered model
  • TEK

ASJC Scopus subject areas

  • General

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