A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
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DOI：
10.1084/jem.20162012
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发表时间：
2017-12-04
期刊：
影响因子：
--
通讯作者：
Medvinsky A
中科院分区：
文献类型：
--
作者：
McGarvey AC;Rybtsov S;Souilhol C;Tamagno S;Rice R;Hills D;Godwin D;Rice D;Tomlinson SR;Medvinsky A
通过小鼠AGM区域的转录谱分析，McGarvey等人鉴定了HSC发育的潜在生态位调节因子。它们显示了BMPER在调节HSC成熟中的新功能，可能通过其对BMP信号传导的调节。在发育中的胚胎中，造血干细胞（HSC）从性腺-中肾（AGM）区域出现，但对这一过程的分子调控知之甚少。最近，从E9.5到E10.5的进展和极性沿着背腹轴已被确定为支持HSC生态位的明确界限。为了鉴定HSC成熟的新型分泌调节因子，我们对AGM区域和支持性OP 9细胞系中的这些时空转换进行了RNA测序。通过体外再聚集培养系统筛选几种蛋白质，我们确定BMPER为一种新的HSC发育的正调节因子。我们证明BMPER与BMP信号传导抑制相关，但由BMP 4转录诱导，这表明BMPER有助于精确控制AGM区域内的BMP活性，从而使HSC在BMP阴性环境中成熟。这些发现和我们的转录数据的可用性，通过一个可访问的接口应该提供深入了解的维护和潜在的衍生培养的HSC。
Through transcriptional profiling of the mouse AGM region, McGarvey et al. identify potential niche regulators of HSC development. They show a new function of BMPER in regulating HSC maturation, likely via its modulation of BMP signalling. 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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DOI：
10.1084/jem.20120993
发表时间：
2013-01-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guiu J;Shimizu R;D'Altri T;Fraser ST;Hatakeyama J;Bresnick EH;Kageyama R;Dzierzak E;Yamamoto M;Espinosa L;Bigas A
通讯作者：
Bigas A
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
16.6
作者：
Gama-Norton L;Ferrando E;Ruiz-Herguido C;Liu Z;Guiu J;Islam AB;Lee SU;Yan M;Guidos CJ;López-Bigas N;Maeda T;Espinosa L;Kopan R;Bigas A
通讯作者：
Bigas A
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
32.4
作者：
Cumano, A;Ferraz, JC;Godin, I
通讯作者：
Godin, I