Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells
Author(s)Chou, Song; Lodish, Harvey F.
MetadataShow full item record
Previously we showed that the ~2% of fetal liver cells reactive with an anti-CD3ε 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 α-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.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
Chou, Song and Harvey F. Lodish."Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells." PNAS, April 27, 2010 vol. 107 no. 17 7799-7804. ©2010 by the National Academy of Sciences.
Final published version