CRB1 is required for recycling by RAB11A+ vesicles in human retinal organoids.

Autor:	Buck TM; Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the Netherlands., Quinn PMJ; Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the Netherlands., Pellissier LP; Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam 1105 BA, the Netherlands., Mulder AA; Department of Cell & Chemical Biology, Leiden University Medical Center (LUMC), Leiden 2300 RC, the Netherlands., Jongejan A; Bioinformatics Laboratory, Epidemiology & Data Science, Amsterdam University Medical Centers, Amsterdam 1105 AZ, the Netherlands., Lu X; Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the Netherlands., Boon N; Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the Netherlands., Koot D; Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the Netherlands., Almushattat H; Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the Netherlands., Arendzen CH; Leiden University Medical Center hiPSC Hotel, Leiden 2333 ZA, the Netherlands., Vos RM; Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam 1105 BA, the Netherlands., Bradley EJ; Department of Genome Analysis, Amsterdam University Medical Centers, Amsterdam 1105 AZ, the Netherlands., Freund C; Leiden University Medical Center hiPSC Hotel, Leiden 2333 ZA, the Netherlands., Mikkers HMM; Department of Cell & Chemical Biology, Leiden University Medical Center (LUMC), Leiden 2300 RC, the Netherlands; Leiden University Medical Center hiPSC Hotel, Leiden 2333 ZA, the Netherlands., Boon CJF; Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the Netherlands; Department of Ophthalmology, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam 1000 AE, the Netherlands., Moerland PD; Bioinformatics Laboratory, Epidemiology & Data Science, Amsterdam University Medical Centers, Amsterdam 1105 AZ, the Netherlands., Baas F; Department of Genome Analysis, Amsterdam University Medical Centers, Amsterdam 1105 AZ, the Netherlands; Department of Clinical Genetics/LDGA, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands., Koster AJ; Department of Cell & Chemical Biology, Leiden University Medical Center (LUMC), Leiden 2300 RC, the Netherlands., Neefjes J; Department of Cell & Chemical Biology, Leiden University Medical Center (LUMC), Leiden 2300 RC, the Netherlands., Berlin I; Department of Cell & Chemical Biology, Leiden University Medical Center (LUMC), Leiden 2300 RC, the Netherlands., Jost CR; Department of Cell & Chemical Biology, Leiden University Medical Center (LUMC), Leiden 2300 RC, the Netherlands., Wijnholds J; Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the Netherlands; Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam 1105 BA, the Netherlands. Electronic address: j.wijnholds@lumc.nl.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2023 Sep 12; Vol. 18 (9), pp. 1793-1810. Date of Electronic Publication: 2023 Aug 03.
DOI:	10.1016/j.stemcr.2023.07.001
Abstrakt:	CRB1 gene mutations can cause early- or late-onset retinitis pigmentosa, Leber congenital amaurosis, or maculopathy. Recapitulating human CRB1 phenotypes in animal models has proven challenging, necessitating the development of alternatives. We generated human induced pluripotent stem cell (iPSC)-derived retinal organoids of patients with retinitis pigmentosa caused by biallelic CRB1 mutations and evaluated them against autologous gene-corrected hiPSCs and hiPSCs from healthy individuals. Patient organoids show decreased levels of CRB1 and NOTCH1 expression at the retinal outer limiting membrane. Proximity ligation assays show that human CRB1 and NOTCH1 can interact via their extracellular domains. CRB1 patient organoids feature increased levels of WDFY1+ vesicles, fewer RAB11A+ recycling endosomes, decreased VPS35 retromer complex components, and more degradative endolysosomal compartments relative to isogenic control organoids. Taken together, our data demonstrate that patient-derived retinal organoids enable modeling of retinal degeneration and highlight the importance of CRB1 in early endosome maturation receptor recycling in the retina. Competing Interests: Conflict of interests The authors declare no competing interests. The LUMC is holder of patent number PCT/NL2014/050549, which describes the potential clinical use of CRB2; J.W. and L.P.P. are listed as co-inventor of this patent, and J.W. is an employee of the LUMC. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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