The mirn23a and mirn23b microrna clusters are necessary for proper hematopoietic progenitor cell production and differentiation.
The mirn23a and mirn23b microrna clusters are necessary for proper hematopoietic progenitor cell production and differentiation.
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DOI：
10.1016/j.exphem.2017.12.007
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发表时间：
2018-03
影响因子：
2.6
通讯作者：
Dahl R
中科院分区：
文献类型：
--
作者：
Kurkewich JL;Boucher A;Klopfenstein N;Baskar R;Kapur R;Dahl R
缺乏 microRNA (miRNA) 簇 mirn23a 的小鼠表现出 B 淋巴细胞生成增加，但以骨髓生成为代价，而造血干细胞和祖细胞 (HSPC) 群体则没有变化。哺乳动物拥有旁系同源的 mirn23b 基因，该基因可以产生 3 种成熟的 miRNA（miR -23b、24-1 和 -27b），这些 miRNA 具有与其 mirn23a 对应物相同的种子/mRNA 靶向序列。为了评估 mirn23a 和 mirn23b 的复合删除是否会加剧 mirn23a−/− 小鼠中观察到的造血表型，我们生成了复合 mirn23a−/−mirn23bfl/fl：Mx1-Cre 条件敲除小鼠，并测定了 mirn23b 切除后的造血发育。成人骨髓中这两个基因的缺失进一步使 HSPC 向 B 细胞分化，而骨髓细胞则受到损害，这表明对调节细胞分化具有剂量依赖性作用。引人注目的是，双基因敲除小鼠的骨髓细胞结构减少，HSC 和祖细胞群显着减少，这种表型在仅缺乏 mirn23a 的小鼠中未观察到。竞争性移植测定显示，移植后 6 周和 12 周时，mirn23a−/−mirn23b−/− HSPC 对造血谱系的贡献降低。没有观察到 mirn23a−/−b−/− HSPC 的增殖缺陷，但与野生型和 mirn23a−/− 细胞相比，双敲除细胞的凋亡率更高。总之，我们的数据表明，mirn23a/mirn23b miRNA 的完全丢失会导致血液产量减少，并以浓度依赖性方式影响谱系输出。
Mice deficient for microRNA (miRNA) cluster mirn23a exhibit increased B lymphopoiesis at the expense of myelopoiesis while hematopoietic stem and progenitor (HSPC) populations are unchanged. Mammals possess a paralogous mirn23b gene that can give rise to 3 mature miRNAs (miRs -23b, 24-1, and -27b) that have identical seed/mRNA targeting sequences to their mirn23a counterparts. To assess whether compound deletion of mirn23a and mirn23b exacerbates the hematopoietic phenotype observed in mirn23a−/− mice, we generated a compound mirn23a−/−mirn23bfl/fl: Mx1-Cre conditional knockout mouse and assayed hematopoietic development after excision of mirn23b. Loss of both genes in adult bone marrow further skewed HSPC differentiation towards B cells at the expense of myeloid cells demonstrating a dosage dependent effect on regulating cell differentiation. Strikingly, double knockout mice had decreased bone marrow cellularity with significantly decreased HSC and progenitor populations, a phenotype not observed in mice deficient for mirn23a alone. Competitive transplant assays showed decreased contribution of mirn23a−/−mirn23b−/− HSPCs to hematopoietic lineages at 6 and 12 weeks post transplant. Defects in the proliferation of mirn23a−/−b−/− HSPCs was not observed, however double knockout cells were more apoptotic compared to both wildtype and mirn23a−/− cells. Together, our data shows that complete loss of mirn23a/mirn23b miRNAs results in decreased blood production and affects lineage output in a concentration dependent manner.
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DOI：
10.1084/jem.20090831
发表时间：
2010-03-15
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Han YC;Park CY;Bhagat G;Zhang J;Wang Y;Fan JB;Liu M;Zou Y;Weissman IL;Gu H
通讯作者：
Gu H
造血干细胞：转录调控，离体扩张和临床应用。
影响因子：
2.5
作者：
Aggarwal R;Lu J;Pompili VJ;Das H
通讯作者：
Das H
影响因子：
8.8
作者：
Park CY;Jeker LT;Carver-Moore K;Oh A;Liu HJ;Cameron R;Richards H;Li Z;Adler D;Yoshinaga Y;Martinez M;Nefadov M;Abbas AK;Weiss A;Lanier LL;de Jong PJ;Bluestone JA;Srivastava D;McManus MT
通讯作者：
McManus MT
影响因子：
2.6
作者：
Kong, Kimi Y.;Owens, Kristin S.;Rogers, Jason H.;Mullenix, Jason;Velu, Chinavenmeni S.;Grimes, H. Leighton;Dahl, Richard
通讯作者：
Dahl, Richard
影响因子：
82.9
作者：
通讯作者：
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