title: Effects of let-7b and TLX on the proliferation and differentiation of retinal progenitor cells in vitro.
abstract: MicroRNAs manifest significant functions in brain neural stem cell (NSC) self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. Let-7b is expressed in the mammalian brain and regulates NSC proliferation and differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal. Whether let-7b and TLX act as important regulators in retinal progenitor cell (RPC) proliferation and differentiation remains unknown. Here, our data show that let-7b and TLX play important roles in controlling RPC fate determination in vitro. Let-7b suppresses TLX expression to negatively regulate RPC proliferation and accelerate the neuronal and glial differentiation of RPCs. The overexpression of let-7b downregulates TLX levels in RPCs, leading to reduced RPC proliferation and increased neuronal and glial differentiation, whereas antisense knockdown of let-7b produces robust TLX expression,enhanced RPC proliferation and decreased differentiation. Moreover, the inhibition of endogenous TLX by small interfering RNA suppresses RPC proliferation and promotes RPC differentiation. Furthermore, overexpression of TLX rescues let-7b-induced proliferation deficiency and weakens the RPC differentiation enhancement caused by let-7b alone. These results suggest that let-7b, by forming a negative feedback loop with TLX, provides a novel model to regulate the proliferation and differentiation of retinal progenitors in vitro.
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Ni
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Junzhao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Mengyu
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C490258:Nr2e1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; C542687:mirnlet7 microRNA, mouse