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.

在发育中的胚胎中，造血干细胞 (HSC) 从主动脉-性腺-中肾 (AGM) 区域出现，但对该过程的分子调控知之甚少。最近，从 E9.5 到 E10.5 的进展以及沿背腹轴的极性已被确定为支持性 HSC 生态位的明确界限。为了识别 HSC 成熟的新分泌调节剂，我们对 AGM 区域和支持性 OP9 细胞系中的这些时空转换进行了 RNA 测序。通过离体再聚集培养系统筛选几种蛋白质，我们将 BMPER 确定为 HSC 发育的新型正调节剂。我们证明 BMPER 与 BMP 信号传导抑制有关，但由 BMP4 转录诱导，表明 BMPER 有助于精确控制 AGM 区域内的 BMP 活性，使 HSC 在 BMP 阴性环境中成熟。这些发现以及我们通过可访问界面获得的转录数据应该可以深入了解 HSC 在培养中的维持和潜在衍生。