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

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 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 Pébay

作者机构：Department of Anatomy and NeuroscienceThe University of MelbourneParkvilleVIC 3010Australia Department of SurgeryThe University of MelbourneParkvilleVIC 3010Australia Centre for Eye Research AustraliaRoyal Victorian Eye and Ear HospitalEast MelbourneVIC 3002Australia Garvan Weizmann Centre for Cellular GenomicsGarvan Institute of Medical ResearchThe Kinghorn Cancer CentreDarlinghurstNSW 2010Australia Single Cell Open Research EndeavourThe Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Immunology DivisionThe Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Department of Medical BiologyThe University of MelbourneParkvilleVIC 3010Australia School of MedicineMenzies Institute for Medical ResearchUniversity of TasmaniaHobartTAS 7005Australia UNSW Cellular Genomics Futures InstituteSchool of Medical SciencesUniversity of New South WalesSydneyNSW 2052Australia 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2021年第19卷第2期

页      面：223-242页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：a National Health and Medical Research Council(NHMRC-Australia)Practitioner Fellowship(awarded to AWH) Career Development Fellowship(awarded to JEP) Senior Research Fellowship(Grant No.1154389,awarded to AP) an Australian Research Council Future Fellowship(Grant No.FT 140100047,awarded to AP) NHMRC project grants(Grant Nos.1138253 awarded to ELF and AP,as well as 1062820 and 1124812 awarded to SHN) a NHMRC synergy grant(Grant No.1181010 awarded to ELF and AP) grants from the Macular Disease Foundation Australia(awarded to AP,JEP AWH) the Jack Brockhoff Foundation(awarded to GEL) the DHB Foundation(awarded to GEL and AP) the Ophthalmic Research Institute of Australia(awarded to AP and AWH) Stem Cells Australia-the Australian Research Council Special Research Initiative in Stem Cell Science(awarded to SHN,AWH,JEP,and AP) the TMG Family Fund(awarded to AP and GEL) 

主　　题：Human embryonic stem cell Human pluripotent stem cell Retinal pigment epithelium Single-cell RNA sequencing Ageing 

摘      要：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.