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Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12151-6. doi: 10.1073/pnas.1407370111. Epub 2014 Aug 4.

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

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Department of Pediatrics, Wells Center for Pediatric Research and.
Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences-Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama 230-0045, Japan.
Department of Pediatrics, Wells Center for Pediatric Research andDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202; and.
Department of Pediatrics, Wells Center for Pediatric Research and


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.


TEK; hemogenic endothelial cell; immune layered model

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