Haematopoietic stem and progenitor cell heterogeneity is inherited from the embryonic endothelium.
Haematopoietic stem and progenitor cell heterogeneity is inherited from the embryonic endothelium.
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DOI：
10.1038/s41556-023-01187-9
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发表时间：
2023-08
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
造血干细胞和祖细胞（HSPC）产生红系、淋巴系和髓系谱系。HSPC在胚胎中通过AGM（Akta-gonad-mesonephros）中的造血内皮细胞的转分化产生。AGM中的HSPC在分化和增殖输出方面是异质的，但这些内在差异是如何获得的仍然没有答案。在这里，我们发现斑马鱼中microRNA（miR）-128的缺失导致AGM中HSPC的扩增，其具有不同的细胞周期状态和向红系和淋巴祖细胞的倾斜。在造血内皮细胞向HSPC转化之前，在分化中操纵miR-128，重现了斑马鱼和人类多能干细胞中的谱系偏斜。miR-128通过转录后抑制Wnt抑制剂csnk 1a 1和Notch配体jag 1b促进AGM中的Wnt和Notch信号传导。cskn 1a 1的去阻遏导致复制型和红细胞偏向的HSPC，而jag 1b的去阻遏导致G2/M和淋巴偏向的HSPC，对各自的血液谱系具有长期影响。我们认为HSPC异质性产生于AGM内皮，部分由Wnt和Notch信号传导编程。Ghersi等人报道造血干细胞和祖细胞异质性建立在造血内皮水平上，并且至少部分地由microRNA-128介导的Wnt和Notch信号传导的调节来调节。
Definitive haematopoietic stem and progenitor cells (HSPCs) generate erythroid, lymphoid and myeloid lineages. HSPCs are produced in the embryo via transdifferentiation of haemogenic endothelial cells in the aorta–gonad–mesonephros (AGM). HSPCs in the AGM are heterogeneous in differentiation and proliferative output, but how these intrinsic differences are acquired remains unanswered. Here we discovered that loss of microRNA (miR)-128 in zebrafish leads to an expansion of HSPCs in the AGM with different cell cycle states and a skew towards erythroid and lymphoid progenitors. Manipulating miR-128 in differentiating haemogenic endothelial cells, before their transition to HSPCs, recapitulated the lineage skewing in both zebrafish and human pluripotent stem cells. miR-128 promotes Wnt and Notch signalling in the AGM via post-transcriptional repression of the Wnt inhibitor csnk1a1 and the Notch ligand jag1b. De-repression of cskn1a1 resulted in replicative and erythroid-biased HSPCs, whereas de-repression of jag1b resulted in G2/M and lymphoid-biased HSPCs with long-term consequence on the respective blood lineages. We propose that HSPC heterogeneity arises in the AGM endothelium and is programmed in part by Wnt and Notch signalling. Ghersi et al. report that haematopoietic stem and progenitor cell heterogeneity is established on the haemogenic endothelium level and is, at least in part, regulated by microRNA-128-mediated modulation of Wnt and Notch signalling.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
人类多能干细胞定向分化确定性造血内皮和造血祖细胞
影响因子：
4.8
作者：
Ditadi, Andrea;Sturgeon, Christopher M.
通讯作者：
Sturgeon, Christopher M.
影响因子：
8.8
作者：
Dignum T;Varnum-Finney B;Srivatsan SR;Dozono S;Waltner O;Heck AM;Ishida T;Nourigat-McKay C;Jackson DL;Rafii S;Trapnell C;Bernstein ID;Hadland B
通讯作者：
Hadland B
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