title: Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells.
abstract: We have developed a coculture system that establishes DLK(+) fetal hepatic progenitors as the authentic supportive cells for expansion of hematopoietic stem (HSCs) and progenitor cells. In 1-week cultures supplemented with serum and supportive cytokines, both cocultured DLK(+) fetal hepatic progenitors and their conditioned medium supported rapid expansion of hematopoietic progenitors and a small increase in HSC numbers. In 2- and 3-week cultures DLK(+) cells, but not their conditioned medium, continuously and significantly (>20-fold) expanded both hematopoietic stem and progenitor cells. Physical contact between HSCs and DLK(+) cells was crucial to maintaining this long-term expansion. Similar HSC expansion (approximately sevenfold) was achieved in cocultures using a serum-free, low cytokine- containing medium. In contrast, DLK(-) cells are incapable of expanding hematopoietic cells, demonstrating that hepatic progenitors are the principle supportive cells for HSC expansion in the fetal liver.
authors: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
authors: Song
authors: S
authors: Chou
authors: Johan
authors: J
authors: Flygare
authors: Harvey F
authors: HF
authors: Lodish
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D005333:Fetus; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D002135:Calcium-Binding Proteins; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D016207:Cytokines; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D049452:Green Fluorescent Proteins