Sox17-Mediated Maintenance of Fetal Intra-Aortic Hematopoietic Cell Clusters

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 t...

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Bibliographic Details
Published in:Molecular and cellular biology 2014-06, Vol.34 (11), p.1976-1990
Main Authors: Nobuhisa, Ikuo, Osawa, Mitsujiro, Uemura, Mami, Kishikawa, Yoko, Anani, Maha, Harada, Kaho, Takagi, Haruna, Saito, Kiyoka, Kanai-Azuma, Masami, Kanai, Yoshiakira, Iwama, Atsushi, Taga, Tetsuya
Format: Article
Language:English
Subjects:
Animals
Aorta - embryology
Bone Marrow Cells - cytology
Bone Marrow Cells - metabolism
Bone Marrow Transplantation
Cell Lineage - genetics
Cells, Cultured
Embryo, Mammalian - cytology
Embryo, Mammalian - metabolism
Gene Expression Regulation, Developmental
Gonads - embryology
Green Fluorescent Proteins - genetics
Hematopoiesis - genetics
Hematopoietic Stem Cells - cytology
HMGB Proteins - genetics
HMGB Proteins - metabolism
Mesonephros - embryology
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
RNA Interference
RNA, Small Interfering
SOXF Transcription Factors - genetics
SOXF Transcription Factors - metabolism
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Summary: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.
ISSN:1098-5549
0270-7306
1098-5549
DOI:10.1128/MCB.01485-13