RRC ID 52211
Author Aldiri I, Xu B, Wang L, Chen X, Hiler D, Griffiths L, Valentine M, Shirinifard A, Thiagarajan S, Sablauer A, Barabas ME, Zhang J, Johnson D, Frase S, Zhou X, Easton J, Zhang J, Mardis ER, Wilson RK, Downing JR, Dyer MA, St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project.
Title The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis.
Journal Neuron
Abstract In the developing retina, multipotent neural progenitors undergo unidirectional differentiation in a precise spatiotemporal order. Here we profile the epigenetic and transcriptional changes that occur during retinogenesis in mice and humans. Although some progenitor genes and cell cycle genes were epigenetically silenced during retinogenesis, the most dramatic change was derepression of cell-type-specific differentiation programs. We identified developmental-stage-specific super-enhancers and showed that most epigenetic changes are conserved in humans and mice. To determine how the epigenome changes during tumorigenesis and reprogramming, we performed integrated epigenetic analysis of murine and human retinoblastomas and induced pluripotent stem cells (iPSCs) derived from murine rod photoreceptors. The retinoblastoma epigenome mapped to the developmental stage when retinal progenitors switch from neurogenic to terminal patterns of cell division. The epigenome of retinoblastomas was more similar to that of the normal retina than that of retina-derived iPSCs, and we identified retina-specific epigenetic memory.
Volume 94(3)
Pages 550-568.e10
Published 2017-5-3
DOI 10.1016/j.neuron.2017.04.022
PII S0896-6273(17)30348-3
PMID 28472656
PMC PMC5508517
MeSH Animals Animals, Genetically Modified Carcinogenesis / genetics* Cell Differentiation / genetics* Cellular Reprogramming / genetics* DNA Methylation / genetics* Disease Models, Animal Epigenesis, Genetic* Histone Code / genetics* Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / metabolism Mice Mouse Embryonic Stem Cells / cytology Mouse Embryonic Stem Cells / metabolism Retina / embryology Retina / metabolism* Retinal Rod Photoreceptor Cells / cytology Retinoblastoma / genetics* Retinoblastoma Protein / genetics
IF 14.415
Times Cited 60
Resource
Human and Animal Cells Rx-GFP K/I EB5(AES0145)