Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina.
Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina.
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DOI：
10.1016/j.celrep.2022.110849
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发表时间：
2022-06-14
期刊：
影响因子：
8.8
通讯作者：
Blackshaw, Seth
中科院分区：
文献类型：
--
作者：
Hoang, Thanh;Kim, Dong Won;Appel, Haley;Pannullo, Nicole A.;Leavey, Patrick;Ozawa, Manabu;Zheng, Sika;Yu, Minzhong;Peachey, Neal S.;Blackshaw, Seth
直接将胶质细胞重编程为神经元是替代因损伤或神经退行性疾病而失去的神经元的一种潜在的有前途的方法。最近有报道称，敲低多嘧啶束结合蛋白Ptbp1可诱导视网膜神经胶质细胞有效转化为功能性神经元。在这里，我们使用遗传谱系追踪、单细胞RNA测序（scRNA-seq）和视网膜电图分析的组合来表明，在成人视网膜<s:1>神经胶质细胞中，选择性诱导pptp1的杂合或纯合功能丧失突变体不会导致任何可检测水平的神经元转换。在pptbp1缺失后，在神经胶质中仅观察到少量基因表达变化，胶质细胞的特性得以维持。这些发现强调了使用遗传操作和谱系追踪方法研究细胞类型转换的重要性。Hoang等人利用Ptbp1在成人视网膜下部<s:1> ller胶质细胞中功能的遗传缺失，表明Ptbp1的缺失不会将成人视网膜下部<s:1> ller胶质细胞转化为神经元，也不会显著改变下部<s:1> ller胶质细胞的转录特性。
Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Müller glia into functional neurons. Here, we use a combination of genetic lineage tracing, single-cell RNA sequencing (scRNA-seq), and electroretinogram analysis to show that selective induction of either heterozygous or homozygous loss-of-function mutants of Ptbp1 in adult retinal Müller glia does not lead to any detectable level of neuronal conversion. Only a few changes in gene expression are observed in Müller glia following Ptbp1 deletion, and glial identity is maintained. These findings highlight the importance of using genetic manipulation and lineage-tracing methods in studying cell-type conversion. Using genetic loss of function of Ptbp1 in adult retinal Müller glia, Hoang et al. show that Ptbp1 deletion does not convert adult retinal Müller glia into neurons or significantly change Müller glial transcriptional identity.
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影响因子：
8.8
作者：
Ling JP;Chhabra R;Merran JD;Schaughency PM;Wheelan SJ;Corden JL;Wong PC
通讯作者：
Wong PC
DOI：
10.1126/science.abb8598
发表时间：
2020-11-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hoang T;Wang J;Boyd P;Wang F;Santiago C;Jiang L;Yoo S;Lahne M;Todd LJ;Jia M;Saez C;Keuthan C;Palazzo I;Squires N;Campbell WA;Rajaii F;Parayil T;Trinh V;Kim DW;Wang G;Campbell LJ;Ash J;Fischer AJ;Hyde DR;Qian J;Blackshaw S
通讯作者：
Blackshaw S
影响因子：
64.8
作者：
Qian H;Kang X;Hu J;Zhang D;Liang Z;Meng F;Zhang X;Xue Y;Maimon R;Dowdy SF;Devaraj NK;Zhou Z;Mobley WC;Cleveland DW;Fu XD
通讯作者：
Fu XD
DOI：
10.1073/pnas.1107488109
发表时间：
2012-03-20
影响因子：
11.1
作者：
de Melo, Jimmy;Miki, Katsuaki;Blackshaw, Seth
通讯作者：
Blackshaw, Seth
影响因子：
64.5
作者：
Xue Y;Ouyang K;Huang J;Zhou Y;Ouyang H;Li H;Wang G;Wu Q;Wei C;Bi Y;Jiang L;Cai Z;Sun H;Zhang K;Zhang Y;Chen J;Fu XD
通讯作者：
Fu XD