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Chromatin Accessibility and Transcriptional Differences in Human Stem Cell-Derived Early-Stage Retinal Organoids.
Jones, Melissa K; Agarwal, Devansh; Mazo, Kevin W; Chopra, Manan; Jurlina, Shawna L; Dash, Nicholas; Xu, Qianlan; Ogata, Anna R; Chow, Melissa; Hill, Alex D; Kambli, Netra K; Xu, Guorong; Sasik, Roman; Birmingham, Amanda; Fisch, Kathleen M; Weinreb, Robert N; Enke, Ray A; Skowronska-Krawczyk, Dorota; Wahlin, Karl J.
Afiliação
  • Jones MK; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Agarwal D; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Mazo KW; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
  • Chopra M; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Jurlina SL; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Dash N; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Xu Q; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Ogata AR; Center for Translational Vision Research, University of California Irvine, Irvine, CA 92617, USA.
  • Chow M; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Hill AD; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Kambli NK; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Xu G; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
  • Sasik R; Department of Biotechnology, California State University Channel Islands, Camarillo, CA 93012, USA.
  • Birmingham A; Center for Computational Biology and Bioinformatics, University of California San Diego, La Jolla, CA 92093, USA.
  • Fisch KM; Center for Computational Biology and Bioinformatics, University of California San Diego, La Jolla, CA 92093, USA.
  • Weinreb RN; Center for Computational Biology and Bioinformatics, University of California San Diego, La Jolla, CA 92093, USA.
  • Enke RA; Center for Computational Biology and Bioinformatics, University of California San Diego, La Jolla, CA 92093, USA.
  • Skowronska-Krawczyk D; Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Diego, La Jolla, CA 92037, USA.
  • Wahlin KJ; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, USA.
Cells ; 11(21)2022 10 28.
Article em En | MEDLINE | ID: mdl-36359808
Retinogenesis involves the specification of retinal cell types during early vertebrate development. While model organisms have been critical for determining the role of dynamic chromatin and cell-type specific transcriptional networks during this process, an enhanced understanding of the developing human retina has been more elusive due to the requirement for human fetal tissue. Pluripotent stem cell (PSC) derived retinal organoids offer an experimentally accessible solution for investigating the developing human retina. To investigate cellular and molecular changes in developing early retinal organoids, we developed SIX6-GFP and VSX2-tdTomato (or VSX2-h2b-mRuby3) dual fluorescent reporters. When differentiated as 3D organoids these expressed GFP at day 15 and tdTomato (or mRuby3) at day 25, respectively. This enabled us to explore transcriptional and chromatin related changes using RNA-seq and ATAC-seq from pluripotency through early retina specification. Pathway analysis of developing organoids revealed a stepwise loss of pluripotency, while optic vesicle and retina pathways became progressively more prevalent. Correlating gene transcription with chromatin accessibility in early eye field development showed that retinal cells underwent a clear change in chromatin landscape, as well as gene expression profiles. While each dataset alone provided valuable information, considering both in parallel provided an informative glimpse into the molecular nature eye development.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Organoides / Células-Tronco Pluripotentes Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Organoides / Células-Tronco Pluripotentes Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article