Indian Institute of Science Education and Research, Mohali, India.
Indian Institute of Science Education and Research, Mohali, India
Life Sci Alliance. 2019 Oct 8;2(5). doi: 10.26508/lsa.201900548. Print 2019 Oct.
Octamer-binding transcription factor 4 (Oct4, also known as Pou5F3) is an essential pluripotency-inducing factor, governing a plethora of biological functions during cellular reprogramming. Retina regeneration in zebrafish involves reprogramming of Müller glia (MG) into a proliferating population of progenitors (MGPCs) with stem cell-like characteristics, along with up-regulation of pluripotency-inducing factors. However, the significance of Oct4 during retina regeneration remains elusive. In this study, we show an early panretinal induction of Oct4, which is essential for MG reprogramming through the regulation of several regeneration-associated factors such as Ascl1a, Lin28a, Sox2, Zeb, E-cadherin, and various miRNAs, namely, , /, and / We also show the crucial roles played by Oct4 during cell cycle exit of MGPCs in collaboration with members of nucleosome remodeling and deacetylase complex such as Hdac1. Notably, Oct4 regulates Tgf-β signaling negatively during MG reprogramming, and positively to cause cycle exit of MGPCs. Our study reveals unique mechanistic involvement of Oct4, during MG reprogramming and cell cycle exit in zebrafish, which may also account for the inefficient retina regeneration in mammals.
八聚体结合转录因子 4（Oct4，也称为 Pou5F3）是一种必需的多能性诱导因子，在细胞重编程过程中控制着大量的生物学功能。斑马鱼的视网膜再生涉及 Müller 胶质细胞（MG）向具有干细胞样特征的增殖祖细胞（MGPC）的重编程，同时上调多能性诱导因子。然而，Oct4 在视网膜再生中的意义仍然难以捉摸。在这项研究中，我们显示了 Oct4 的全视网膜早期诱导，这对于通过调节几个与再生相关的因子（如 Ascl1a、Lin28a、Sox2、Zeb、E-cadherin 和各种 miRNA，即 miR-124、miR-143 和 miR-200c）来调控 MG 重编程是必需的。我们还表明，Oct4 与核小体重塑和去乙酰化酶复合物（如 Hdac1）的成员一起，在 MGPCs 的细胞周期退出过程中发挥着关键作用。值得注意的是，Oct4 在 MG 重编程期间负调控 TGF-β 信号，而在 MGPCs 的细胞周期退出期间正调控 TGF-β 信号。我们的研究揭示了 Oct4 在斑马鱼 MG 重编程和细胞周期退出过程中的独特机制参与，这也可能解释了哺乳动物中效率低下的视网膜再生。
