Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates Epithelial Progenitor Expansion during Organogenesis.
Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates Epithelial Progenitor Expansion during Organogenesis.
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DOI：
10.1016/j.devcel.2016.12.001
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发表时间：
2017-01-09
影响因子：
11.8
通讯作者：
Hoffman MP
中科院分区：
文献类型：
--
作者：
Hayashi T;Lombaert IM;Hauser BR;Patel VN;Hoffman MP
上皮-间充质相互作用涉及器官发生期间组织之间的基本通信，并且主要由生长因子和细胞外基质调节。目前还不清楚含有RNA的外泌体是否是调节上皮-间充质相互作用的移动的遗传信号。在这里，我们确定了加载有间充质特异性成熟miRNA的外泌体贡献了从间充质到上皮的移动的遗传信号。加载到外泌体中的成熟间充质miR-133 b-3 p从间充质转运到不表达原代miR-133 b-3 p的唾液上皮。在培养物中敲低miR-133 B-3 p降低了终芽形态发生，减少了上皮KIT+祖细胞的增殖，并增加了靶基因Disco相互作用蛋白2同源物B（Dip 2 B）的表达。DIP 2B参与DNA甲基化，在有丝分裂期间与5-甲基胞嘧啶一起定位于KIT+祖细胞亚群的前期细胞核中。总之，miR-133 b-3 p从间充质到上皮的外泌体转运减少了DIP 2B，DIP 2B可能在器官发生期间充当负责KIT+祖细胞扩增的基因的表观遗传调节剂。
Epithelial-mesenchymal interactions involve fundamental communication between tissues during organogenesis and are primarily regulated by growth factors and extracellular matrix. It is unclear whether RNA-containing exosomes are mobile genetic signals regulating epithelial-mesenchymal interactions. Here we identify that exosomes loaded with mesenchyme-specific mature miRNA contribute mobile genetic signals from mesenchyme to epithelium. The mature mesenchymal miR-133b-3p, loaded into exosomes was transported from mesenchyme to the salivary epithelium, which did not express primary miR-133b-3p. Knockdown of miR-133b-3p in culture decreased endbud morphogenesis, reduced proliferation of epithelial KIT+ progenitors and increased expression of a target gene, Disco-interacting protein 2 homolog B (Dip2b). DIP2B, which is involved in DNA methylation, was localized with 5-methylcytosine in the prophase nucleus of a subset of KIT+ progenitors during mitosis. In summary, exosomal transport of miR-133b-3p from mesenchyme to epithelium decreases DIP2B, which may function as an epigenetic regulator of genes responsible for KIT+ progenitor expansion during organogenesis.
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影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
影响因子：
3.7
作者：
Kosaka N;Ochiya T
通讯作者：
Ochiya T
影响因子：
5.4
作者：
Edgar JR
通讯作者：
Edgar JR
影响因子：
2.7
作者：
Hayashi, Toru;Koyama, Noriko;Kashimata, Masanori
通讯作者：
Kashimata, Masanori
影响因子：
4.6
作者：
Rebustini, Ivan T.;Hayashi, Toru;Hoffman, Matthew P.
通讯作者：
Hoffman, Matthew P.