An interactive resource of molecular signalling in the developing human haematopoietic stem cell niche.
An interactive resource of molecular signalling in the developing human haematopoietic stem cell niche.
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DOI：
10.1242/dev.201972
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发表时间：
2023-12-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
主动脉-性腺-中肾 (AGM) 区域中从卡内基期 (CS) 14 到 CS17 的最终人类造血干细胞 (HSC) 的出现是一个严格调控的过程。此前，我们对该时期末的人类 AGM 区域（CS16/CS17）进行了空间转录组分析，并鉴定了参与 HSC 发育的分泌因子。在这里，我们扩展了我们的分析，以研究在 HSC 出现的整个时期内背主动脉周围的背腹极化信号的进展。我们的结果表明，CS13-CS14 转变过程中腹侧信号复杂性急剧增加，这与最终 HSC 的首次出现相一致。我们进一步观察到 CS17 信号传导的阶段特异性变化，这可能支持小鼠模型中描述的 HSC 的逐步成熟。在线界面中还提供了丰富的数据资源，可以对 AGM 区域的空间定义域之间的分子相互作用进行计算机分析。对于研究人类 HSC 发育机制的研究人员以及开发从多能干细胞生成临床相关 HSC 的体外方法的研究人员来说，该资源将特别感兴趣。摘要：在空间和单细胞水平上对人类发育造血干细胞生态位中的分子信号传导进行深入和交互式探索。
The emergence of definitive human haematopoietic stem cells (HSCs) from Carnegie Stage (CS) 14 to CS17 in the aorta-gonad-mesonephros (AGM) region is a tightly regulated process. Previously, we conducted spatial transcriptomic analysis of the human AGM region at the end of this period (CS16/CS17) and identified secreted factors involved in HSC development. Here, we extend our analysis to investigate the progression of dorso-ventral polarised signalling around the dorsal aorta over the entire period of HSC emergence. Our results reveal a dramatic increase in ventral signalling complexity from the CS13-CS14 transition, coinciding with the first appearance of definitive HSCs. We further observe stage-specific changes in signalling up to CS17, which may underpin the step-wise maturation of HSCs described in the mouse model. The data-rich resource is also presented in an online interface enabling in silico analysis of molecular interactions between spatially defined domains of the AGM region. This resource will be of particular interest for researchers studying mechanisms underlying human HSC development as well as those developing in vitro methods for the generation of clinically relevant HSCs from pluripotent stem cells. Summary: An in-depth and interactive exploration of molecular signalling in the human developmental haematopoietic stem cell niche at the spatial and single cell level.
影响因子：
5.2
作者：
Gur-Cohen S;Kollet O;Graf C;Esmon CT;Ruf W;Lapidot T
通讯作者：
Lapidot T
DOI：
10.1016/j.regen.2021.100050
发表时间：
2021-08
期刊：
Journal of immunology and regenerative medicine
影响因子：
--
作者：
Fidanza A;Forrester LM
通讯作者：
Forrester LM
影响因子：
11.8
作者：
Wilkinson, Robert N.;Pouget, Claire;Gering, Martin;Russell, Angela J.;Davies, Stephen G.;Kimelman, David;Patient, Roger
通讯作者：
Patient, Roger