title: Hematopoietic stem cells from fancc(-/-) mice have lower growth and differentiation potential in response to growth factors.
abstract: Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow (BM) failure. We have previously shown that stem cells from the FA group C mouse model have lower long-term primary and secondary reconstitution ability, and that bone marrow of Fancc(-/-) mice contained fewer lineage-negative (Lin(-))Thy1.2(low)Sca-1(+)c-kit(+) CD34(+) cells but normal levels of Lin(-)Thy1.2(low)Sca-1(+)c-kit(+)CD34(-) primitive cells. These data suggest that CD34(+) primitive cells have either a lower growth or differentiation potential, or that these cells have greater apoptosis levels. To investigate the role Fancc might have on the growth and differentiation potentials of primitive hematopoietic stem cells, we used a single-cell culture system and monitored cell viability, doubling potential, and apoptosis levels of Fancc(-/-) primitive Lin(-)Thy1.2(-)Sca-1(+) (LTS)-CD34(+) and LTS-CD34(-) stem cells. Results showed that Fancc(-/-) LTS-CD34(-) and LTS-CD34(+) cells had altered growth and apoptosis responses to combinations of stimulatory cytokines, most dramatically in response to a combination of factors that included interleukin-3 (IL-3) and IL-6. In addition, Fancc(-/-) LTS-CD34(-) and LTS-CD34(+) cells showed a lower differentiation potential than Fancc(+/+) cells. These results support a role for Fancc in the growth and differentiation of primitive hematopoietic cells and suggest that an altered response to stimulatory cytokines may contribute to BM aplasia in FA patients.
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004351:Drug Resistance / Q000235:genetics* / Q000276:immunology; D005199:Fanconi Anemia / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D007377:Interleukin-3 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019089:Stem Cell Factor / Q000378:metabolism / Q000494:pharmacology; D013926:Thrombopoietin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018952:Antigens, CD34; D018797:Cell Cycle Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; C497652:Fancc protein, mouse; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D007377:Interleukin-3; D015850:Interleukin-6; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011506:Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D013926:Thrombopoietin