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

Alison C McGarvey, Stanislav Rybtsov, Céline Souilhol, Sara Tamagno, Ritva Rice, David Hills, Duncan Godwin, David Rice, Simon R Tomlinson, Alexander Medvinsky

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3731-3751
Number of pages21
JournalJournal of Experimental Medicine
Volume214
Issue number12
DOIs
Publication statusPublished - 1 Nov 2017

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