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Publication : A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.

First Author  McGarvey AC Year  2017
Journal  J Exp Med Volume  214
Issue  12 Pages  3731-3751
PubMed ID  29093060 Mgi Jnum  J:251966
Mgi Id  MGI:6106548 Doi  10.1084/jem.20162012
Citation  McGarvey AC, et al. (2017) A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation. J Exp Med 214(12):3731-3751
abstractText  In the developing embryo, hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region, but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA sequencing over these spatiotemporal transitions in the AGM region and supportive OP9 cell line. Screening several proteins through an ex vivo reaggregate culture system, we identify BMPER as a novel positive regulator of HSC development. We demonstrate that BMPER is associated with BMP signaling inhibition, but is transcriptionally induced by BMP4, suggesting that BMPER contributes to the precise control of BMP activity within the AGM region, enabling the maturation of HSCs within a BMP-negative environment. These findings and the availability of our transcriptional data through an accessible interface should provide insight into the maintenance and potential derivation of HSCs in culture.
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