RT Journal Article
SR Electronic
T1 Oct4 mediates Müller glia reprogramming and cell cycle exit during retina regeneration in zebrafish
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900548
DO 10.26508/lsa.201900548
VO 2
IS 5
A1 Poonam Sharma
A1 Shivangi Gupta
A1 Mansi Chaudhary
A1 Soumitra Mitra
A1 Bindia Chawla
A1 Mohammad Anwar Khursheed
A1 Rajesh Ramachandran
YR 2019
UL https://www.life-science-alliance.org/content/2/5/e201900548.abstract
AB 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, let-7a, miR-200a/miR-200b, and miR-143/miR-145. 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.