title: Sox17-mediated maintenance of fetal intra-aortic hematopoietic cell clusters.
abstract: During mouse development, definitive hematopoiesis is first detected around embryonic day 10.5 (E10.5) in the aorta-gonad-mesonephros (AGM) region, which exhibits intra-aortic cell clusters. These clusters are known to contain hematopoietic stem cells (HSCs). On the other hand, it is not clear how the cells in such clusters maintain their HSC phenotype and how they are triggered to differentiate. Here we found that an endodermal transcription factor marker, Sox17, and other F-group (SoxF) proteins, Sox7 and Sox18, were expressed in E10.5 intra-aortic cell clusters. Forced expression of any of these SoxF proteins, particularly Sox17, in E10.5 AGM CD45(low) c-Kit(high) cells, which are the major component of intra-aortic clusters, led to consistent formation of cell clusters in vitro during several passages of cocultures with stromal cells. Cluster-forming cells with constitutive Sox17 expression retained long-term bone marrow reconstitution activity in vivo. Notably, shutdown of exogenously introduced Sox17 gene expression resulted in immediate hematopoietic differentiation. These results indicate that SoxF proteins, especially Sox17, contribute to the maintenance of cell clusters containing HSCs in the midgestation AGM region. Furthermore, SoxF proteins play a pivotal role in controlling the HSC fate decision between indefinite self-renewal and differentiation during fetal hematopoiesis.
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nobuhisa
authors.forename: Mitsujiro
authors.initials: M
authors.lastname: Osawa
authors.forename: Mami
authors.initials: M
authors.lastname: Uemura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kishikawa
authors.forename: Maha
authors.initials: M
authors.lastname: Anani
authors.forename: Kaho
authors.initials: K
authors.lastname: Harada
authors.forename: Haruna
authors.initials: H
authors.lastname: Takagi
authors.forename: Kiyoka
authors.initials: K
authors.lastname: Saito
authors.forename: Masami
authors.initials: M
authors.lastname: Kanai-Azuma
authors.forename: Yoshiakira
authors.initials: Y
authors.lastname: Kanai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iwama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taga
mesh_terms: D000818:Animals; D001011:Aorta / Q000196:embryology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000196:embryology; D049452:Green Fluorescent Proteins / Q000235:genetics; D024002:HMGB Proteins / Q000235:genetics* / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008650:Mesonephros / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D034622:RNA Interference; D034741:RNA, Small Interfering; D055760:SOXF Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D024002:HMGB Proteins; D034741:RNA, Small Interfering; D055760:SOXF Transcription Factors; C511606:Sox17 protein, mouse; C490653:Sox18 protein, mouse; C102515:Sox7 protein, mouse; D049452:Green Fluorescent Proteins