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

TitleA molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
Publication TypeJournal Article
Year of Publication2017
AuthorsMcGarvey AC, Rybtsov S, Souilhol C, Tamagno S, Rice R, Hills D, Godwin D, Rice D, Tomlinson SR, Medvinsky A
JournalJ Exp Med
Volume214
Issue12
Pagination3731-3751
Date Published2017 Dec 04
ISSN1540-9538
KeywordsAnimals, Aorta, Bone Morphogenetic Proteins, Carrier Proteins, Cell Differentiation, Cluster Analysis, Feedback, Physiological, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gonads, Hematopoietic Stem Cells, Mesoderm, Mesonephros, Mice, Inbred C57BL, Signal Transduction, Smad Proteins, Stem Cell Niche, Time Factors
Abstract

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.

DOI10.1084/jem.20162012
Alternate JournalJ. Exp. Med.
PubMed ID29093060
PubMed Central IDPMC5716029
Grant List / / Wellcome Trust / United Kingdom
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