title: Expression of Pitx2 in stromal cells is required for normal hematopoiesis.
abstract: Although the expression of Pitx2, a bicoid family homeodomain transcription factor, is highly regulated during hematopoiesis, its function during this process was not documented; we thus studied hematopoiesis in Pitx2-null mice. We found that Pitx2(-/-) embryos display hypoplastic livers with reduced numbers of hematopoietic cells, but these cells had normal hematopoietic potential, as evidenced by colony-forming assays, immature progenitor cell assays, and long-term repopulation assays. Because the microenvironment is also crucial to the development of normal hematopoiesis, we established Pitx2(-/-) and Pitx2(+/+) stromas from fetal liver and studied their hematopoietic supportive capacity. We showed that the frequency of cobblestone area-forming cells was 4-fold decreased when using Pitx2(-/-) stromal cells compared with Pitx2(+/+) stromal cells, whatever the Pitx2 genotype of hematopoietic cells tested in this assay. This defect was rescued by expression of Pitx2 into Pitx2(-/-) fetal liver stromal cells, demonstrating a major and direct role of Pitx2 in the hematopoietic supportive capacity of fetal liver stroma. Finally, we showed a reduced capacity of MS5 stromal cells expressing Pitx2 RNAi to support human hematopoiesis. Altogether these data showed that Pitx2 has major functions in the hematopoietic supportive capacity of fetal liver and adult bone marrow stromal cells.
authors.affiliation: Institut Cochin, Département d'Hématologie, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kieusseian
authors.forename: Jalila
authors.initials: J
authors.lastname: Chagraoui
authors.forename: Cécile
authors.initials: C
authors.lastname: Kerdudo
authors.forename: Philippe-Emmanuel
authors.initials: PE
authors.lastname: Mangeot
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Gage
authors.forename: Nicole
authors.initials: N
authors.lastname: Navarro
authors.forename: Brigitte
authors.initials: B
authors.lastname: Izac
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Forget
authors.forename: Anne
authors.initials: A
authors.lastname: Dubart-Kupperschmitt
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006720:Homozygote; D016086:Lentivirus / Q000235:genetics; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2