4.8 Article

Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1003586107

Keywords

bone marrow transplantation; growth factors; hematopoiesis; stem cell niche

Funding

  1. National Institutes of Health (NIH) [DK067356]

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Previously we showed that the similar to 2% of fetal liver cells reactive with an anti-CD3 epsilon monoclonal antibody support ex vivo expansion of both fetal liver and bone marrow hematopoietic stem cells (HSCs); these cells express two proteins important for HSC ex vivo expansion, IGF2, and angiopoietin-like 3. Here we show that these cells do not express any CD3 protein and are not T cells; rather, we purified these HSC-supportive stromal cells based on the surface phenotype of SCF+DLK+. Competitive repopulating experiments showthat SCF+DLK+ cells support themaintenance of HSCs in ex vivo culture. These are the principal fetal liver cells that express not only angiopoietin-like 3 and IGF2, but also SCF and thrombopoietin, two other growth factors important for HSC expansion. They are also the principal fetal liver cells that express CXCL12, a factor required for HSC homing, and also a-fetoprotein (AFP), indicating that they are fetal hepatic stem or progenitor cells. Immunocytochemistry shows that>93% of the SCF+ cells express DLK and Angptl3, and a portion of SCF+ cells also expresses CXCL12. Thus SCF+DLK+ cells are a highly homogenous population that express a complete set of factors for HSC expansion and are likely the primary stromal cells that support HSC expansion in the fetal liver.

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