Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation.
Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation.
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DOI：
10.3389/fncel.2022.1096872
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发表时间：
2022
影响因子：
5.3
通讯作者：
White, Patricia M.
中科院分区：
文献类型：
--
作者：
Piekna-Przybylska, Dorota;Na, Daxiang;Zhang, Jingyuan;Baker, Cameron;Ashton, John M.;White, Patricia M.
耳蜗毛细胞(Hcs)死亡引起的听力损失可以通过支持细胞(SCs)的脱分化和增殖来恢复，就像在鸟类中观察到的那样。在之前的一篇报道中，ERBB2在一组耳蜗干细胞中的激活促进了邻近细胞中SOX2的广泛下调，促进了HC样细胞的增殖和分化。在这里，我们分析了激活ERBB2的新生小鼠耳蜗干细胞的单细胞转录本，目的是识别潜在的分泌效应物。ERBB2在体内的诱导产生了一个新的细胞群体，该细胞具有基因网络的从头表达。这些配体和它们的调节器被称为小整合素结合配体n连接的糖蛋白(兄弟)，可以改变Noch信号并促进细胞在其他系统中的存活、增殖和分化。我们验证了网络成员的mRNA表达，然后将我们的分析扩展到更老的阶段。年轻成体干细胞中的ERBB2信号也促进了基因网络成员的蛋白表达。此外，我们还在Corti器官中发现了增殖的耳蜗胞聚体。我们的结果表明，ERBB2信号在耳蜗干细胞中的异位激活可以改变微环境，促进细胞增殖和细胞重排。综上所述，这些结果提示了一种在成年哺乳动物耳蜗中诱导干细胞样活性的新机制。
Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. We validated mRNA expression of network members, and then extended our analysis to older stages. ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. Furthermore, we found proliferating cochlear cell aggregates in the organ of Corti. Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea.
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影响因子：
8.8
作者：
Jan TA;Eltawil Y;Ling AH;Chen L;Ellwanger DC;Heller S;Cheng AG
通讯作者：
Cheng AG
影响因子：
11.2
作者：
Garg P;Sarma D;Jeppsson S;Patel NR;Gewirtz AT;Merlin D;Sitaraman SV
通讯作者：
Sitaraman SV
影响因子：
7.3
作者：
Burns JC;Stone JS
通讯作者：
Stone JS
影响因子：
5.2
作者：
Hedberg-Oldfors, Carola;Darin, Niklas;Oldfors, Anders
通讯作者：
Oldfors, Anders
影响因子：
56.9
作者：
CORWIN, JT;COTANCHE, DA
通讯作者：
COTANCHE, DA