Augmented Production of Platelets From Cord Blood With Euchromatic Histone Lysine Methyltransferase Inhibition.
Augmented Production of Platelets From Cord Blood With Euchromatic Histone Lysine Methyltransferase Inhibition.
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通过抑制常染色质组蛋白赖氨酸甲基转移酶来提高脐带血血小板的产量
DOI：
10.1093/stcltm/szac048
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发表时间：
2022-09-21
影响因子：
6
通讯作者：
中科院分区：
文献类型：
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作者：
脐带血造血干/祖细胞（CB-HSPCs）作为一种有前途的功能性血小板来源，有望缓解日益增长的血小板输注需求，但其分子机制不明确和血小板生成不足限制了其临床应用。在这里，我们对超过16160个细胞进行了单细胞分析，以构建CB-HSPC人类巨核细胞生成的动态分子景观，使我们能够首次发现新生巨核细胞（MK）的细胞异质性和独特特征，并为科学界提供独特的资源。通过使用该模型，我们定义了从巨核细胞-红系祖细胞（MEP）通过巨核细胞祖细胞（MKP）分化为MK的分化过程的遗传程序，并确定了常染色质组蛋白赖氨酸甲基转移酶（EHMT）的抑制剂，当在分化的早期阶段应用时，可显著增加最终的血小板生成。在机制水平上，我们发现EHMT抑制剂选择性地诱导MEP和MKP的扩增。总之，我们发现了人类巨核细胞生成的新机制，并为未来血小板的大规模生成和临床应用提供了一种新的化学策略。
Cord blood hematopoietic stem/progenitor cells (CB-HSPCs) have emerged as a promising supply for functional platelets to potentially alleviate the increasing demand for platelet transfusions, but the clinical application has been limited by the undefined molecular mechanism and insufficient platelet production. Here, we performed single-cell profiling of more than 16 160 cells to construct a dynamic molecular landscape of human megakaryopoiesis from CB-HSPCs, enabling us to uncover, for the first time, cellular heterogeneity and unique features of neonatal megakaryocytes (MKs) and to also offer unique resources for the scientific community. By using this model, we defined the genetic programs underlying the differentiation process from megakaryocyte-erythroid progenitors (MEPs) to MKs via megakaryocyte progenitors (MKPs) and identified inhibitors of euchromatic histone lysine methyltransferase (EHMT), which, when applied at the early stage of differentiation, significantly increase the final platelet production. At the mechanistic level, we found that EHMT inhibitors act to selectively induce the expansion of MEPs and MKPs. Together, we uncover new mechanistic insights into human megakaryopoiesis and provide a novel chemical strategy for future large-scale generation and clinical applications of platelets.
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DOI：
10.1083/jcb.201304054
发表时间：
2013-06-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Machlus KR;Italiano JE Jr
通讯作者：
Italiano JE Jr
影响因子：
20.6
作者：
Xie X;Liu M;Zhang Y;Wang B;Zhu C;Wang C;Li Q;Huo Y;Guo J;Xu C;Hu L;Pang A;Ma S;Wang L;Cao W;Chen S;Li Q;Zhang S;Zhao X;Zhou W;Luo H;Zheng G;Jiang E;Feng S;Chen L;Shi L;Cheng H;Hao S;Zhu P;Cheng T
通讯作者：
Cheng T
影响因子：
6
作者：
Liu C;Huang B;Wang H;Zhou J
通讯作者：
Zhou J
人类巨核细胞的细胞异质性和免疫亚群的表征
DOI：
10.1002/advs.202100921
发表时间：
2021-08
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Liu C;Wu D;Xia M;Li M;Sun Z;Shen B;Liu Y;Jiang E;Wang H;Su P;Shi L;Xiao Z;Zhu X;Zhou W;Wang Q;Gao X;Cheng T;Zhou J
通讯作者：
Zhou J
影响因子：
4.2
作者：
Sweis, Ramzi F.;Pliushchev, Marina;Pappano, William N.
通讯作者：
Pappano, William N.