{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:42:53Z","timestamp":1760150573421,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Western New York Stem Cell Science","award":["(WNYSTEM Grant 2015)","(CRF Grant 2012)"],"award-info":[{"award-number":["(WNYSTEM Grant 2015)","(CRF Grant 2012)"]}]},{"name":"The Cystinosis Research Foundation","award":["(WNYSTEM Grant 2015)","(CRF Grant 2012)"],"award-info":[{"award-number":["(WNYSTEM Grant 2015)","(CRF Grant 2012)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystinosis is an autosomal recessive disease resulting from mutations in ctns, which encodes for cystinosin, a proton-coupled cystine transporter that exports cystine from lysosomes. The major clinical form, infantile cystinosis, is associated with renal failure due to the malfunctioning of the renal proximal tubule (RPT). To examine the hypothesis that the malfunctioning of the cystinotic RPT arises from defective differentiation, human-induced pluripotent stem cells (hiPSCs) were generated from human dermal fibroblasts from an individual with infantile cystinosis, as well as a normal individual. The results indicate that both the cystinotic and normal hiPSCs are pluripotent and can form embryoid bodies (EBs) with the three primordial germ layers. When the normal hiPSCs were subjected to a differentiation regime that induces RPT formation, organoids containing tubules with lumens emerged that expressed distinctive RPT proteins, including villin, the Na+\/H+ Exchanger (NHE) isoform 3 (NHE3), and the NHE Regulatory Factor 1 (NHERF1). The formation of tubules with lumens was less pronounced in organoids derived from cystinotic hiPSCs, although the organoids expressed villin, NHE3, and NHERF1. These observations can be attributed to an impairment in differentiation and\/or by other defects which cause cystinotic RPTs to have an increased propensity to undergo apoptosis or other types of programmed cell death.<\/jats:p>","DOI":"10.3390\/ijms242317004","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T09:39:12Z","timestamp":1701337152000},"page":"17004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Studies with Human-Induced Pluripotent Stem Cells Reveal That CTNS Mutations Can Alter Renal Proximal Tubule Differentiation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0188-7363","authenticated-orcid":false,"given":"Ramkumar","family":"Thiyagarajan","sequence":"first","affiliation":[{"name":"Division of Geriatric Medicine, University of Kansas Medical Center, University of Kansas, Kansas City, KS 66160, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-3885","authenticated-orcid":false,"given":"Mary","family":"Taub","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1093\/hmg\/ddh152","article-title":"Molecular pathogenesis of cystinosis: Effect of CTNS mutations on the transport activity and subcellular localization of cystinosin","volume":"13","author":"Kalatzis","year":"2004","journal-title":"Hum. 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