The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis

St. Jude Children's Research Hospital—Washington University Pediatric Cancer Genome Project

doi:10.1016/j.neuron.2017.04.022

The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis

St. Jude Children's Research Hospital—Washington University Pediatric Cancer Genome Project

Research output: Contribution to journal › Article › peer-review

186 Scopus citations

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.

Original language	English (US)
Pages (from-to)	550-568.e10
Journal	Neuron
Volume	94
Issue number	3
DOIs	https://doi.org/10.1016/j.neuron.2017.04.022
State	Published - May 3 2017
Externally published	Yes

Keywords

DNA methylation
epigenetic memory
epigenetics
iPSCs
retinal development
retinoblastoma
rod photoreceptors

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2017.04.022

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title = "The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis",

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.",

keywords = "DNA methylation, epigenetic memory, epigenetics, iPSCs, retinal development, retinoblastoma, rod photoreceptors",

author = "{St. Jude Children's Research Hospital—Washington University Pediatric Cancer Genome Project} and Issam Aldiri and Beisi Xu and Lu Wang and Xiang Chen and Daniel Hiler and Lyra Griffiths and Marc Valentine and Abbas Shirinifard and Suresh Thiagarajan and Andras Sablauer and Barabas, {Marie Elizabeth} and Jiakun Zhang and Dianna Johnson and Sharon Frase and Xin Zhou and John Easton and Jinghui Zhang and Mardis, {Elaine R.} and Wilson, {Richard K.} and Downing, {James R.} and Dyer, {Michael A.}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

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doi = "10.1016/j.neuron.2017.04.022",

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AU - St. Jude Children's Research Hospital—Washington University Pediatric Cancer Genome Project

AU - Aldiri, Issam

AU - Xu, Beisi

AU - Wang, Lu

AU - Chen, Xiang

AU - Hiler, Daniel

AU - Griffiths, Lyra

AU - Valentine, Marc

AU - Shirinifard, Abbas

AU - Thiagarajan, Suresh

AU - Sablauer, Andras

AU - Barabas, Marie Elizabeth

AU - Zhang, Jiakun

AU - Johnson, Dianna

AU - Frase, Sharon

AU - Zhou, Xin

AU - Easton, John

AU - Zhang, Jinghui

AU - Mardis, Elaine R.

AU - Wilson, Richard K.

AU - Downing, James R.

AU - Dyer, Michael A.

PY - 2017/5/3

Y1 - 2017/5/3

N2 - 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.

AB - 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.

KW - DNA methylation

KW - epigenetic memory

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KW - iPSCs

KW - retinal development

KW - retinoblastoma

KW - rod photoreceptors

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The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis

Abstract

Keywords

ASJC Scopus subject areas

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