The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate.

The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate.
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DOI:
10.1371/journal.pgen.1002403
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发表时间:
2011-12
期刊:
影响因子:
4.5
通讯作者:
Frye M
Frye M
中科院分区:
生物学2区
文献类型:
--
作者:
Blanco S;Kurowski A;Nichols J;Watt FM;Benitah SA;Frye M

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大多数成体组织的动态平衡是通过平衡干细胞的自我更新和分化来维持的,但转录后机制是否能够调节这一过程尚不清楚。在这里,我们确定了RNA甲基转移酶(MISU/NSUN2)是平衡干细胞自我更新和皮肤分化所必需的。在表皮中,这种甲基转移酶存在于特定亚群的毛囊干细胞中,这种亚群的毛囊干细胞准备进行谱系承诺,它的耗尽会导致干细胞的静止和异常分化。我们的结果表明,转录后RNA甲基化可以在控制干细胞命运方面发挥以前没有被认识到的作用。我们证明,MISU/NSUN2的RNA甲基转移酶活性是维持表皮分化程序所必需的,因此转录后机制参与控制干细胞自我更新和分化之间的平衡。
Homeostasis of most adult tissues is maintained by balancing stem cell self-renewal and differentiation, but whether post-transcriptional mechanisms can regulate this process is unknown. Here, we identify that an RNA methyltransferase (Misu/Nsun2) is required to balance stem cell self-renewal and differentiation in skin. In the epidermis, this methyltransferase is found in a defined sub-population of hair follicle stem cells poised to undergo lineage commitment, and its depletion results in enhanced quiescence and aberrant stem cell differentiation. Our results reveal that post-transcriptional RNA methylation can play a previously unappreciated role in controlling stem cell fate. We demonstrate that the RNA methyltransferase activity of Misu/NSun2 is required for the proper maintenance of the epidermal differentiation program, and thus post-transcriptional mechanisms are involved in controlling the balance between stem cell self-renewal and differentiation.
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