Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells.
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.
Chou
Song
S
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Lodish
Harvey F
HF
D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism; D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; C513121:IGF2 protein, mouse; D000509:alpha-Fetoproteins; D007335:Insulin-Like Growth Factor II
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