Loading…

Novel roles for voltage‐gated T‐type Ca2+ and ClC‐2 channels in phagocytosis and angiogenic factor balance identified in human iPSC‐derived RPE

Human‐induced pluripotent stem cell (hiPSC)‐derived retinal pigment epithelium (RPE) is a powerful tool for pathophysiological studies and preclinical therapeutic screening, as well as a source for clinical cell transplantation. Thus, it must be validated for maturity and functionality to ensure cor...

Full description

Saved in:
Bibliographic Details
Published in:The FASEB journal 2021-04, Vol.35 (4), p.e21406-n/a
Main Authors: Mamaeva, Daria, Jazouli, Zhour, DiFrancesco, Mattia L., Erkilic, Nejla, Dubois, Gregor, Hilaire, Cecile, Meunier, Isabelle, Boukhaddaoui, Hassan, Kalatzis, Vasiliki
Format: Article
Language:English
Subjects:
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page n/a
container_issue 4
container_start_page e21406
container_title The FASEB journal
container_volume 35
creator Mamaeva, Daria
Jazouli, Zhour
DiFrancesco, Mattia L.
Erkilic, Nejla
Dubois, Gregor
Hilaire, Cecile
Meunier, Isabelle
Boukhaddaoui, Hassan
Kalatzis, Vasiliki
description Human‐induced pluripotent stem cell (hiPSC)‐derived retinal pigment epithelium (RPE) is a powerful tool for pathophysiological studies and preclinical therapeutic screening, as well as a source for clinical cell transplantation. Thus, it must be validated for maturity and functionality to ensure correct data readouts and clinical safety. Previous studies have validated hiPSC‐derived RPE as morphologically characteristic of the tissue in the human eye. However, information concerning the expression and functionality of ion channels is still limited. We screened hiPSC‐derived RPE for the polarized expression of a panel of L‐type (CaV1.1, CaV1.3) and T‐type (CaV3.1, CaV3.3) Ca2+ channels, K+ channels (Maxi‐K, Kir4.1, Kir7.1), and the Cl− channel ClC‐2 known to be expressed in native RPE. We also tested the roles of these channels in key RPE functions using specific inhibitors. In addition to confirming the native expression profiles and function of certain channels, such as L‐type Ca2+ channels, we show for the first time that T‐type Ca2+ channels play a role in both phagocytosis and vascular endothelial growth factor (VEGF) secretion. Moreover, we demonstrate that Maxi‐K and Kir7.1 channels are involved in the polarized secretion of VEGF and pigment epithelium‐derived factor (PEDF). Furthermore, we show a novel localization for ClC‐2 channel on the apical side of hiPSC‐derived RPE, with an overexpression at the level of fluid‐filled domes, and demonstrate that it plays an important role in phagocytosis, as well as VEGF and PEDF secretion. Taken together, hiPSC‐derived RPE is a powerful model for advancing fundamental knowledge of RPE functions.
doi_str_mv 10.1096/fj.202002754R
format article
fullrecord <record><control><sourceid>proquest_wiley</sourceid><recordid>TN_cdi_proquest_miscellaneous_2501851184</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2501851184</sourcerecordid><originalsourceid>FETCH-LOGICAL-p1636-96eb3916290896d08e0fcd94fa44541cebe1f4df8b27446022dc1f7fe1fa03ce3</originalsourceid><addsrcrecordid>eNpFkM1u2zAQhImiAeomOebOY4BA7pKiaOmYCHZbIEiC_JwFmlrKNGhSFWUHvuURcsv79UlKJwVy2sVg9sPOEHLGYMqgkj_MesqBA_BZIe6_kAkrcshkKeErmUBZ8UzKvPxGvse4BgAGTE7I203YoaNDcBipCQPdBTeqDv--vHZqxJY-pm3c90hrxS-o8i2tXZ00TvVKeY8uUutpv1Jd0PsxRBvfTcp3NnToraZG6TGBl8opr5HaFv1ojU3sdLjabpSn9u7hwGxxsLuk39_NT8iRUS7i6f95TJ4W88f6V3Z9-_N3fXmd9UzmMqskLvOKSV6lgLKFEsHothJGCVEIpnGJzIjWlEs-E0IC561mZmaSqiDXmB-T8w9uP4Q_W4xjs7FRo0u_YtjGhhfAyoKxUiSr-LA-W4f7ph_sRg37hkFzaL8x6-az_WbxcMU5EyDzf-r5fuA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2501851184</pqid></control><display><type>article</type><title>Novel roles for voltage‐gated T‐type Ca2+ and ClC‐2 channels in phagocytosis and angiogenic factor balance identified in human iPSC‐derived RPE</title><source>Wiley:Jisc Collections:Wiley Read and Publish Open Access 2024-2025 (reading list)</source><creator>Mamaeva, Daria ; Jazouli, Zhour ; DiFrancesco, Mattia L. ; Erkilic, Nejla ; Dubois, Gregor ; Hilaire, Cecile ; Meunier, Isabelle ; Boukhaddaoui, Hassan ; Kalatzis, Vasiliki</creator><creatorcontrib>Mamaeva, Daria ; Jazouli, Zhour ; DiFrancesco, Mattia L. ; Erkilic, Nejla ; Dubois, Gregor ; Hilaire, Cecile ; Meunier, Isabelle ; Boukhaddaoui, Hassan ; Kalatzis, Vasiliki</creatorcontrib><description>Human‐induced pluripotent stem cell (hiPSC)‐derived retinal pigment epithelium (RPE) is a powerful tool for pathophysiological studies and preclinical therapeutic screening, as well as a source for clinical cell transplantation. Thus, it must be validated for maturity and functionality to ensure correct data readouts and clinical safety. Previous studies have validated hiPSC‐derived RPE as morphologically characteristic of the tissue in the human eye. However, information concerning the expression and functionality of ion channels is still limited. We screened hiPSC‐derived RPE for the polarized expression of a panel of L‐type (CaV1.1, CaV1.3) and T‐type (CaV3.1, CaV3.3) Ca2+ channels, K+ channels (Maxi‐K, Kir4.1, Kir7.1), and the Cl− channel ClC‐2 known to be expressed in native RPE. We also tested the roles of these channels in key RPE functions using specific inhibitors. In addition to confirming the native expression profiles and function of certain channels, such as L‐type Ca2+ channels, we show for the first time that T‐type Ca2+ channels play a role in both phagocytosis and vascular endothelial growth factor (VEGF) secretion. Moreover, we demonstrate that Maxi‐K and Kir7.1 channels are involved in the polarized secretion of VEGF and pigment epithelium‐derived factor (PEDF). Furthermore, we show a novel localization for ClC‐2 channel on the apical side of hiPSC‐derived RPE, with an overexpression at the level of fluid‐filled domes, and demonstrate that it plays an important role in phagocytosis, as well as VEGF and PEDF secretion. Taken together, hiPSC‐derived RPE is a powerful model for advancing fundamental knowledge of RPE functions.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.202002754R</identifier><language>eng</language><subject>Ca2+ and K+ channels ; ClC‐2 chloride channel ; iPSC‐derived RPE ; phagocytosis ; secretion</subject><ispartof>The FASEB journal, 2021-04, Vol.35 (4), p.e21406-n/a</ispartof><rights>2021 Federation of American Societies for Experimental Biology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-9626-8807</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Mamaeva, Daria</creatorcontrib><creatorcontrib>Jazouli, Zhour</creatorcontrib><creatorcontrib>DiFrancesco, Mattia L.</creatorcontrib><creatorcontrib>Erkilic, Nejla</creatorcontrib><creatorcontrib>Dubois, Gregor</creatorcontrib><creatorcontrib>Hilaire, Cecile</creatorcontrib><creatorcontrib>Meunier, Isabelle</creatorcontrib><creatorcontrib>Boukhaddaoui, Hassan</creatorcontrib><creatorcontrib>Kalatzis, Vasiliki</creatorcontrib><title>Novel roles for voltage‐gated T‐type Ca2+ and ClC‐2 channels in phagocytosis and angiogenic factor balance identified in human iPSC‐derived RPE</title><title>The FASEB journal</title><description>Human‐induced pluripotent stem cell (hiPSC)‐derived retinal pigment epithelium (RPE) is a powerful tool for pathophysiological studies and preclinical therapeutic screening, as well as a source for clinical cell transplantation. Thus, it must be validated for maturity and functionality to ensure correct data readouts and clinical safety. Previous studies have validated hiPSC‐derived RPE as morphologically characteristic of the tissue in the human eye. However, information concerning the expression and functionality of ion channels is still limited. We screened hiPSC‐derived RPE for the polarized expression of a panel of L‐type (CaV1.1, CaV1.3) and T‐type (CaV3.1, CaV3.3) Ca2+ channels, K+ channels (Maxi‐K, Kir4.1, Kir7.1), and the Cl− channel ClC‐2 known to be expressed in native RPE. We also tested the roles of these channels in key RPE functions using specific inhibitors. In addition to confirming the native expression profiles and function of certain channels, such as L‐type Ca2+ channels, we show for the first time that T‐type Ca2+ channels play a role in both phagocytosis and vascular endothelial growth factor (VEGF) secretion. Moreover, we demonstrate that Maxi‐K and Kir7.1 channels are involved in the polarized secretion of VEGF and pigment epithelium‐derived factor (PEDF). Furthermore, we show a novel localization for ClC‐2 channel on the apical side of hiPSC‐derived RPE, with an overexpression at the level of fluid‐filled domes, and demonstrate that it plays an important role in phagocytosis, as well as VEGF and PEDF secretion. Taken together, hiPSC‐derived RPE is a powerful model for advancing fundamental knowledge of RPE functions.</description><subject>Ca2+ and K+ channels</subject><subject>ClC‐2 chloride channel</subject><subject>iPSC‐derived RPE</subject><subject>phagocytosis</subject><subject>secretion</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpFkM1u2zAQhImiAeomOebOY4BA7pKiaOmYCHZbIEiC_JwFmlrKNGhSFWUHvuURcsv79UlKJwVy2sVg9sPOEHLGYMqgkj_MesqBA_BZIe6_kAkrcshkKeErmUBZ8UzKvPxGvse4BgAGTE7I203YoaNDcBipCQPdBTeqDv--vHZqxJY-pm3c90hrxS-o8i2tXZ00TvVKeY8uUutpv1Jd0PsxRBvfTcp3NnToraZG6TGBl8opr5HaFv1ojU3sdLjabpSn9u7hwGxxsLuk39_NT8iRUS7i6f95TJ4W88f6V3Z9-_N3fXmd9UzmMqskLvOKSV6lgLKFEsHothJGCVEIpnGJzIjWlEs-E0IC561mZmaSqiDXmB-T8w9uP4Q_W4xjs7FRo0u_YtjGhhfAyoKxUiSr-LA-W4f7ph_sRg37hkFzaL8x6-az_WbxcMU5EyDzf-r5fuA</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Mamaeva, Daria</creator><creator>Jazouli, Zhour</creator><creator>DiFrancesco, Mattia L.</creator><creator>Erkilic, Nejla</creator><creator>Dubois, Gregor</creator><creator>Hilaire, Cecile</creator><creator>Meunier, Isabelle</creator><creator>Boukhaddaoui, Hassan</creator><creator>Kalatzis, Vasiliki</creator><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9626-8807</orcidid></search><sort><creationdate>202104</creationdate><title>Novel roles for voltage‐gated T‐type Ca2+ and ClC‐2 channels in phagocytosis and angiogenic factor balance identified in human iPSC‐derived RPE</title><author>Mamaeva, Daria ; Jazouli, Zhour ; DiFrancesco, Mattia L. ; Erkilic, Nejla ; Dubois, Gregor ; Hilaire, Cecile ; Meunier, Isabelle ; Boukhaddaoui, Hassan ; Kalatzis, Vasiliki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p1636-96eb3916290896d08e0fcd94fa44541cebe1f4df8b27446022dc1f7fe1fa03ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Ca2+ and K+ channels</topic><topic>ClC‐2 chloride channel</topic><topic>iPSC‐derived RPE</topic><topic>phagocytosis</topic><topic>secretion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mamaeva, Daria</creatorcontrib><creatorcontrib>Jazouli, Zhour</creatorcontrib><creatorcontrib>DiFrancesco, Mattia L.</creatorcontrib><creatorcontrib>Erkilic, Nejla</creatorcontrib><creatorcontrib>Dubois, Gregor</creatorcontrib><creatorcontrib>Hilaire, Cecile</creatorcontrib><creatorcontrib>Meunier, Isabelle</creatorcontrib><creatorcontrib>Boukhaddaoui, Hassan</creatorcontrib><creatorcontrib>Kalatzis, Vasiliki</creatorcontrib><collection>MEDLINE - Academic</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mamaeva, Daria</au><au>Jazouli, Zhour</au><au>DiFrancesco, Mattia L.</au><au>Erkilic, Nejla</au><au>Dubois, Gregor</au><au>Hilaire, Cecile</au><au>Meunier, Isabelle</au><au>Boukhaddaoui, Hassan</au><au>Kalatzis, Vasiliki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel roles for voltage‐gated T‐type Ca2+ and ClC‐2 channels in phagocytosis and angiogenic factor balance identified in human iPSC‐derived RPE</atitle><jtitle>The FASEB journal</jtitle><date>2021-04</date><risdate>2021</risdate><volume>35</volume><issue>4</issue><spage>e21406</spage><epage>n/a</epage><pages>e21406-n/a</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Human‐induced pluripotent stem cell (hiPSC)‐derived retinal pigment epithelium (RPE) is a powerful tool for pathophysiological studies and preclinical therapeutic screening, as well as a source for clinical cell transplantation. Thus, it must be validated for maturity and functionality to ensure correct data readouts and clinical safety. Previous studies have validated hiPSC‐derived RPE as morphologically characteristic of the tissue in the human eye. However, information concerning the expression and functionality of ion channels is still limited. We screened hiPSC‐derived RPE for the polarized expression of a panel of L‐type (CaV1.1, CaV1.3) and T‐type (CaV3.1, CaV3.3) Ca2+ channels, K+ channels (Maxi‐K, Kir4.1, Kir7.1), and the Cl− channel ClC‐2 known to be expressed in native RPE. We also tested the roles of these channels in key RPE functions using specific inhibitors. In addition to confirming the native expression profiles and function of certain channels, such as L‐type Ca2+ channels, we show for the first time that T‐type Ca2+ channels play a role in both phagocytosis and vascular endothelial growth factor (VEGF) secretion. Moreover, we demonstrate that Maxi‐K and Kir7.1 channels are involved in the polarized secretion of VEGF and pigment epithelium‐derived factor (PEDF). Furthermore, we show a novel localization for ClC‐2 channel on the apical side of hiPSC‐derived RPE, with an overexpression at the level of fluid‐filled domes, and demonstrate that it plays an important role in phagocytosis, as well as VEGF and PEDF secretion. Taken together, hiPSC‐derived RPE is a powerful model for advancing fundamental knowledge of RPE functions.</abstract><doi>10.1096/fj.202002754R</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-9626-8807</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 0892-6638
ispartof The FASEB journal, 2021-04, Vol.35 (4), p.e21406-n/a
issn 0892-6638
1530-6860
language eng
recordid cdi_proquest_miscellaneous_2501851184
source Wiley:Jisc Collections:Wiley Read and Publish Open Access 2024-2025 (reading list)
subjects Ca2+ and K+ channels
ClC‐2 chloride channel
iPSC‐derived RPE
phagocytosis
secretion
title Novel roles for voltage‐gated T‐type Ca2+ and ClC‐2 channels in phagocytosis and angiogenic factor balance identified in human iPSC‐derived RPE
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T21%3A50%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_wiley&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Novel%20roles%20for%20voltage%E2%80%90gated%20T%E2%80%90type%20Ca2+%20and%20ClC%E2%80%902%20channels%20in%20phagocytosis%20and%20angiogenic%20factor%20balance%20identified%20in%20human%20iPSC%E2%80%90derived%20RPE&rft.jtitle=The%20FASEB%20journal&rft.au=Mamaeva,%20Daria&rft.date=2021-04&rft.volume=35&rft.issue=4&rft.spage=e21406&rft.epage=n/a&rft.pages=e21406-n/a&rft.issn=0892-6638&rft.eissn=1530-6860&rft_id=info:doi/10.1096/fj.202002754R&rft_dat=%3Cproquest_wiley%3E2501851184%3C/proquest_wiley%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-p1636-96eb3916290896d08e0fcd94fa44541cebe1f4df8b27446022dc1f7fe1fa03ce3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2501851184&rft_id=info:pmid/&rfr_iscdi=true