First Author | Chou S | Year | 2010 |
Journal | Proc Natl Acad Sci U S A | Volume | 107 |
Issue | 17 | Pages | 7799-804 |
PubMed ID | 20385801 | Mgi Jnum | J:159378 |
Mgi Id | MGI:4442525 | Doi | 10.1073/pnas.1003586107 |
Citation | Chou S, et al. (2010) Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells. Proc Natl Acad Sci U S A 107(17):7799-804 |
abstractText | Previously we showed that the ~2% of fetal liver cells reactive with an anti-CD3epsilon 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 show that SCF(+)DLK(+) cells support the maintenance 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 alpha-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. |