Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells.
Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells.
复制标题
Med23 充当造血干细胞骨髓潜能的看门人。
DOI：
10.1038/s41467-018-06282-2
复制
发表时间：
2018-09-14
影响因子：
16.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Chen X;Zhao J;Gu C;Cui Y;Dai Y;Song G;Liu H;Shen H;Liu Y;Wang Y;Xing H;Zhu X;Hao P;Guo F;Liu X
为了应对清髓性应激，HSC被迅速激活以补充髓系祖细胞，同时保持自我更新的全部潜力以确保终身造血。然而，在生理应激过程中协调HSC活动的关键因素在很大程度上仍然未知。在这里，我们报告说，Med23控制激活的造血干细胞的骨髓潜能。造血系统中Med23的消融导致淋巴细胞减少。Med23缺陷的HSC经历骨髓偏向性分化并失去自我更新能力。有趣的是，Med23缺陷型HSC更容易在生理应激下被激活。从机制上讲，Med23在维持干细胞基因表达和抑制髓系基因表达方面起着重要作用。Med23在HSC中下调，并且Med23缺失导致清髓性应激下更好的存活。总之，我们的研究结果确定Med23作为造血干细胞的髓样潜能的看门人，从而提供了独特的见解Med23介导的转录调控，造血干细胞的髓样潜能和造血干细胞激活应激之间的关系。骨髓中的造血干细胞（HSC）是静止的，但在应激反应中被激活。在这里，作者表明Med23的缺失导致HSC响应于应激的更大激活和增强的骨髓潜能，Med23也维持了干细胞基因表达并抑制了骨髓基因。
In response to myeloablative stresses, HSCs are rapidly activated to replenish myeloid progenitors, while maintaining full potential of self-renewal to ensure life-long hematopoiesis. However, the key factors that orchestrate HSC activities during physiological stresses remain largely unknown. Here we report that Med23 controls the myeloid potential of activated HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Med23-deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are much easier to be activated in response to physiological stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is downregulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identify Med23 as a gatekeeper of myeloid potential of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid potential of HSCs and HSC activation upon stresses. Hematopoietic stem cells (HSCs) in the bone marrow are quiescent, but are activated in response to stress. Here, the authors show that loss of Med23 leads to greater activation and enhanced myeloid potential of HSCs in response to stress, also Med23 maintains stemness gene expression and suppresses myeloid genes.
登录
查看更多内容
影响因子：
82.9
作者：
通讯作者：
--
小鼠胚胎头部作为造血干细胞发育的场所
影响因子：
23.9
作者：
Li, Zhuan;Lan, Yu;Liu, Bing
通讯作者：
Liu, Bing
人类原始生殖细胞的转录组和 DNA 甲基化组景观
影响因子：
64.5
作者：
Guo, Fan;Yan, Liying;Qiao, Jie
通讯作者：
Qiao, Jie
MED12独立于介质激酶活性来控制HSC特异性增强剂以控制造血。
影响因子：
23.9
作者：
Aranda-Orgilles B;Saldaña-Meyer R;Wang E;Trompouki E;Fassl A;Lau S;Mullenders J;Rocha PP;Raviram R;Guillamot M;Sánchez-Díaz M;Wang K;Kayembe C;Zhang N;Amoasii L;Choudhuri A;Skok JA;Schober M;Reinberg D;Sicinski P;Schrewe H;Tsirigos A;Zon LI;Aifantis I
通讯作者：
Aifantis I
影响因子：
56.9
作者：
Hashimoto, Satoru;Boissel, Sarah;Colleaux, Laurence
通讯作者：
Colleaux, Laurence