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Transcriptomic Profiling of Human Pluripotent Stem Cell-derived Retinal Pigment Epithelium over Time

Genomics, Proteomics & Bioinformatics 2021年第2期19卷 223-242页

作者： Grace E.Lidgerwood anne senabouth Casey J.A.Smith-Anttila Vikkitharan Gnanasambandapillai Dominik C.Kaczorowski Daniela Amann-Zalcenstein Erica L.Fletcher Shalin H.Naik Alex W.Hewitt Joseph E.Powell Alice Pebay Department of Anatomy and Neuroscience The University of MelbourneParkvilleVIC 3010Australia Department of Surgery The University of MelbourneParkvilleVIC 3010Australia Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC 3002Australia Garvan Weizmann Centre for Cellular Genomics Garvan Institute of Medical ResearchThe Kinghorn Cancer CentreDarlinghurstNSW 2010Australia Single Cell Open Research Endeavour The Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Immunology Division The Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Department of Medical Biology The University of MelbourneParkvilleVIC 3010Australia School of Medicine Menzies Institute for Medical ResearchUniversity of TasmaniaHobartTAS 7005Australia UNSW Cellular Genomics Futures Institute School of Medical SciencesUniversity of New South WalesSydneyNSW 2052Australia

Human pluripotent stem cell(h PSC)-derived progenies are immature versions of cells,presenting a potential limitation to the accurate modelling of diseases associated with maturity or ***,it is important to characterise how closely cells used in culture resemble their native *** order to select appropriate time points of retinal pigment epithelium(RPE)cultures that reflect native counterparts,we characterised the transcriptomic profiles of the h PSC-derived RPE cells from 1-and 12-month *** differentiated the human embryonic stem cell line H9 into RPE cells,performed single-cell RNA-sequencing of a total of 16,576 cells to assess themolecular changes of the RPE cells across these two culture time *** results indicate the stability of the RPE transcriptomic signature,with no evidence of an epithelial–mesenchymal transition,and with the maturing populations of the RPE observed with time in *** of Gene Ontology pathways revealed that as the cultures age,RPE cells upregulate expression of genes involved in metal binding and antioxidant *** might reflect an increased ability to handle oxidative stress as cells *** with native human RPE data confirms a maturing transcriptional profile of RPE cells in *** results suggest that long-term in vitro culture of RPE cells allows the modelling of specific phenotypes observed in native mature *** work highlights the transcriptional landscape of h PSC-derived RPE cells as they age in culture,which provides a reference for native and patient samples to be benchmarked against.

关键词： Human embryonic stem cell Human pluripotent stem cell Retinal pigment epithelium Single-cell RNA sequencing Ageing

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