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|a Chou, Song
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|a Massachusetts Institute of Technology. Department of Biology
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|a Whitehead Institute for Biomedical Research
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|a Lodish, Harvey F.
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|a Chou, Song
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|a Lodish, Harvey F.
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|a Lodish, Harvey F
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|a Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells
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|b National Academy of Sciences,
|c 2011-03-03T18:40:37Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/61386
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|a 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.
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|a National Institutes of Health (U.S.) (NIH) Grant DK067356)
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|a National Institutes of Health (U.S.) (NIH National Research Service Award Fellowship)
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|a en_US
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|a Article
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|t Proceedings of the National Academy of Sciences of the United States of America
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