<?xml version="1.0" encoding="utf-8"?>
<TEI xmlns="http://www.tei-c.org/ns/1.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:hal="http://hal.archives-ouvertes.fr/" xmlns:gml="http://www.opengis.net/gml/3.3/" xmlns:gmlce="http://www.opengis.net/gml/3.3/ce" version="1.1" xsi:schemaLocation="http://www.tei-c.org/ns/1.0 http://api.archives-ouvertes.fr/documents/aofr-sword.xsd">
  <teiHeader>
    <fileDesc>
      <titleStmt>
        <title>HAL TEI export of hal-01233240</title>
      </titleStmt>
      <publicationStmt>
        <distributor>CCSD</distributor>
        <availability status="restricted">
          <licence target="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1.0 - Universal</licence>
        </availability>
        <date when="2026-05-12T20:44:37+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia</title>
            <author role="aut">
              <persName>
                <forename type="first">Karim</forename>
                <surname>Si-Tayeb</surname>
              </persName>
              <email type="md5">66b4f1a529750a6a12eea8b5d3cd13a5</email>
              <email type="domain">inserm.fr</email>
              <idno type="idhal" notation="numeric">950195</idno>
              <idno type="halauthorid" notation="string">264758-950195</idno>
              <idno type="ORCID">https://orcid.org/0000-0003-4599-7441</idno>
              <idno type="IDREF">https://www.idref.fr/087483211</idno>
              <affiliation ref="#struct-182196"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Salam</forename>
                <surname>Idriss</surname>
              </persName>
              <idno type="halauthorid">968504-0</idno>
              <affiliation ref="#struct-182196"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Benoite</forename>
                <surname>Champon</surname>
              </persName>
              <idno type="halauthorid">516502-0</idno>
              <affiliation ref="#struct-182196"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Amandine</forename>
                <surname>Caillaud</surname>
              </persName>
              <email type="md5">a13d247447cde4e315e2fa70fc68893c</email>
              <email type="domain">univ-nantes.fr</email>
              <idno type="idhal" notation="string">amandine-caillaud</idno>
              <idno type="idhal" notation="numeric">1192867</idno>
              <idno type="halauthorid" notation="string">787869-1192867</idno>
              <idno type="ORCID">https://orcid.org/0000-0001-6409-2336</idno>
              <affiliation ref="#struct-182196"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Matthieu</forename>
                <surname>Pichelin</surname>
              </persName>
              <idno type="idhal" notation="numeric">1189031</idno>
              <idno type="halauthorid" notation="string">968505-1189031</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-6822-6132</idno>
              <affiliation ref="#struct-182196"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Lucie</forename>
                <surname>Arnaud</surname>
              </persName>
              <idno type="halauthorid">968506-0</idno>
              <affiliation ref="#struct-182196"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Patricia</forename>
                <surname>Lemarchand</surname>
              </persName>
              <email type="md5">bcee5c776e9e6053aa72acd9a570efb4</email>
              <email type="domain">univ-nantes.fr</email>
              <ptr type="url" target="https://www.univ-nantes.fr/patricia-lemarchand"/>
              <idno type="idhal" notation="string">patricia-lemarchand</idno>
              <idno type="idhal" notation="numeric">740416</idno>
              <idno type="halauthorid" notation="string">39018-740416</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/C-3247-2011</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-5330-2008</idno>
              <idno type="GOOGLE SCHOLAR">https://scholar.google.fr/citations?user=RHZwxCwAAAAJ&amp;hl=fr</idno>
              <idno type="IDREF">https://www.idref.fr/09290419X</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/C-3247-2011</idno>
              <affiliation ref="#struct-182196"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Cedric</forename>
                <surname>Le May</surname>
              </persName>
              <email type="md5">6b11eb547cec1040c6b9b89af990ed11</email>
              <email type="domain">univ-nantes.fr</email>
              <idno type="idhal" notation="string">cedric-le-may</idno>
              <idno type="idhal" notation="numeric">739600</idno>
              <idno type="halauthorid" notation="string">51853-739600</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-7554-792X</idno>
              <idno type="IDREF">https://www.idref.fr/089049853</idno>
              <affiliation ref="#struct-182196"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Kazem</forename>
                <surname>Zibara</surname>
              </persName>
              <idno type="idhal" notation="numeric">774971</idno>
              <idno type="halauthorid" notation="string">943705-774971</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-9887-072X</idno>
              <idno type="IDREF">https://www.idref.fr/151759235</idno>
              <orgName ref="#struct-303340"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Bertrand</forename>
                <surname>Cariou</surname>
              </persName>
              <email type="md5">1eed1f2b671cbc31cf91c6a2af157d87</email>
              <email type="domain">univ-nantes.fr</email>
              <idno type="idhal" notation="numeric">761594</idno>
              <idno type="halauthorid" notation="string">410249-761594</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-1580-8040</idno>
              <idno type="IDREF">https://www.idref.fr/075934981</idno>
              <affiliation ref="#struct-182196"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>Karim</forename>
                <surname>Si-Tayeb</surname>
              </persName>
              <email type="md5">5b7acd97ae65900bab2e0b020750485f</email>
              <email type="domain">univ-nantes.fr</email>
            </editor>
            <funder ref="#projeurop-92449"/>
            <funder>This work was supported by grants from the VaCaRMe project funded by the Région Pays de la Loire (K.S.-T., S.I., B.Cariou), the FP7 Marie Curie IRG 277188/IPSMILD (K.S.-T.), the CHU of Nantes (K.S.-T.), the Leducq Fundation (K.S.-T., C.L.M., B.Cariou), the Cariplo Fundazione (B.Cariou), the Fondation Genavie (K.S.-T., B.Cariou) and the Lebanese University President grant (K.Z.).</funder>
          </titleStmt>
          <editionStmt>
            <edition n="v1" type="current">
              <date type="whenSubmitted">2015-11-24 17:12:34</date>
              <date type="whenModified">2026-04-14 17:07:58</date>
              <date type="whenReleased">2015-11-27 13:26:05</date>
              <date type="whenProduced">2015-11-19</date>
              <date type="whenEndEmbargoed">2015-11-24</date>
              <ref type="file" target="https://hal.science/hal-01233240v1/document">
                <date notBefore="2015-11-24"/>
              </ref>
              <ref type="file" subtype="publisherPaid" n="1" target="https://hal.science/hal-01233240v1/file/Si-Tayeb%20et%20al%20DMM2015%20Urine-sample-derived%20human%20induced%20pluripotent%20stem%20cells%20as%20a%20model%20to%20study%20PCSK9-mediated%20autosomal%20dominant%20hypercholesterolemia.pdf" id="file-1233240-1312304">
                <date notBefore="2015-11-24"/>
              </ref>
              <ref type="externalLink" target="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728336"/>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="326520">
                <persName>
                  <forename>Karim</forename>
                  <surname>Si-Tayeb</surname>
                </persName>
                <email type="md5">5b7acd97ae65900bab2e0b020750485f</email>
                <email type="domain">univ-nantes.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-01233240</idno>
            <idno type="halUri">https://hal.science/hal-01233240</idno>
            <idno type="halBibtex">sitayeb:hal-01233240</idno>
            <idno type="halRefHtml">&lt;i&gt;Disease Models &amp; Mechanisms&lt;/i&gt;, 2015, &lt;a target="_blank" href="https://dx.doi.org/10.1242/dmm.022277"&gt;&amp;#x27E8;10.1242/dmm.022277&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">Disease Models &amp; Mechanisms, 2015, &amp;#x27E8;10.1242/dmm.022277&amp;#x27E9;</idno>
            <availability status="restricted">
              <licence target="https://about.hal.science/hal-authorisation-v1/">HAL Authorization<ref corresp="#file-1233240-1312304"/></licence>
            </availability>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno>
            <idno type="stamp" n="UNIV-NANTES">Université de Nantes</idno>
            <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
            <idno type="stamp" n="CARDIO" corresp="INSERM">Cardiovasculaire</idno>
            <idno type="stamp" n="OPENAIRE">OpenAIRE</idno>
            <idno type="stamp" n="THORAX-UMR">L'unité de recherche de l'institut du thorax (INSERM UMR1087, CNRS UMR6291)</idno>
            <idno type="stamp" n="NANTES-UNIVERSITE">Nantes Université</idno>
            <idno type="stamp" n="UNIV-NANTES-AV2022">Université de Nantes</idno>
            <idno type="stamp" n="UFR-MEDECINE-NANTES">UFR de médecine - Nantes Université</idno>
          </seriesStmt>
          <notesStmt>
            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>
            <biblStruct>
              <analytic>
                <title xml:lang="en">Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Karim</forename>
                    <surname>Si-Tayeb</surname>
                  </persName>
                  <email type="md5">66b4f1a529750a6a12eea8b5d3cd13a5</email>
                  <email type="domain">inserm.fr</email>
                  <idno type="idhal" notation="numeric">950195</idno>
                  <idno type="halauthorid" notation="string">264758-950195</idno>
                  <idno type="ORCID">https://orcid.org/0000-0003-4599-7441</idno>
                  <idno type="IDREF">https://www.idref.fr/087483211</idno>
                  <affiliation ref="#struct-182196"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Salam</forename>
                    <surname>Idriss</surname>
                  </persName>
                  <idno type="halauthorid">968504-0</idno>
                  <affiliation ref="#struct-182196"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Benoite</forename>
                    <surname>Champon</surname>
                  </persName>
                  <idno type="halauthorid">516502-0</idno>
                  <affiliation ref="#struct-182196"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Amandine</forename>
                    <surname>Caillaud</surname>
                  </persName>
                  <email type="md5">a13d247447cde4e315e2fa70fc68893c</email>
                  <email type="domain">univ-nantes.fr</email>
                  <idno type="idhal" notation="string">amandine-caillaud</idno>
                  <idno type="idhal" notation="numeric">1192867</idno>
                  <idno type="halauthorid" notation="string">787869-1192867</idno>
                  <idno type="ORCID">https://orcid.org/0000-0001-6409-2336</idno>
                  <affiliation ref="#struct-182196"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Matthieu</forename>
                    <surname>Pichelin</surname>
                  </persName>
                  <idno type="idhal" notation="numeric">1189031</idno>
                  <idno type="halauthorid" notation="string">968505-1189031</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-6822-6132</idno>
                  <affiliation ref="#struct-182196"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Lucie</forename>
                    <surname>Arnaud</surname>
                  </persName>
                  <idno type="halauthorid">968506-0</idno>
                  <affiliation ref="#struct-182196"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Patricia</forename>
                    <surname>Lemarchand</surname>
                  </persName>
                  <email type="md5">bcee5c776e9e6053aa72acd9a570efb4</email>
                  <email type="domain">univ-nantes.fr</email>
                  <ptr type="url" target="https://www.univ-nantes.fr/patricia-lemarchand"/>
                  <idno type="idhal" notation="string">patricia-lemarchand</idno>
                  <idno type="idhal" notation="numeric">740416</idno>
                  <idno type="halauthorid" notation="string">39018-740416</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/C-3247-2011</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-5330-2008</idno>
                  <idno type="GOOGLE SCHOLAR">https://scholar.google.fr/citations?user=RHZwxCwAAAAJ&amp;hl=fr</idno>
                  <idno type="IDREF">https://www.idref.fr/09290419X</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/C-3247-2011</idno>
                  <affiliation ref="#struct-182196"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Cedric</forename>
                    <surname>Le May</surname>
                  </persName>
                  <email type="md5">6b11eb547cec1040c6b9b89af990ed11</email>
                  <email type="domain">univ-nantes.fr</email>
                  <idno type="idhal" notation="string">cedric-le-may</idno>
                  <idno type="idhal" notation="numeric">739600</idno>
                  <idno type="halauthorid" notation="string">51853-739600</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-7554-792X</idno>
                  <idno type="IDREF">https://www.idref.fr/089049853</idno>
                  <affiliation ref="#struct-182196"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Kazem</forename>
                    <surname>Zibara</surname>
                  </persName>
                  <idno type="idhal" notation="numeric">774971</idno>
                  <idno type="halauthorid" notation="string">943705-774971</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-9887-072X</idno>
                  <idno type="IDREF">https://www.idref.fr/151759235</idno>
                  <orgName ref="#struct-303340"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Bertrand</forename>
                    <surname>Cariou</surname>
                  </persName>
                  <email type="md5">1eed1f2b671cbc31cf91c6a2af157d87</email>
                  <email type="domain">univ-nantes.fr</email>
                  <idno type="idhal" notation="numeric">761594</idno>
                  <idno type="halauthorid" notation="string">410249-761594</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-1580-8040</idno>
                  <idno type="IDREF">https://www.idref.fr/075934981</idno>
                  <affiliation ref="#struct-182196"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">82879</idno>
                <idno type="issn">1754-8403</idno>
                <idno type="eissn">1754-8411</idno>
                <title level="j">Disease Models &amp; Mechanisms</title>
                <imprint>
                  <publisher> Cambridge Company of Biologists</publisher>
                  <date type="datePub">2015-11-19</date>
                  <date type="dateEpub">2015-11-19</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1242/dmm.022277</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <keywords scheme="author">
                <term xml:lang="en">PCSK9</term>
                <term xml:lang="en">Autosomal dominant hypercholesterolemia</term>
                <term xml:lang="en">Urine-derived somatic cells</term>
                <term xml:lang="en">Hepatocyte differentiation</term>
                <term xml:lang="en">Human induced pluripotent stem cells</term>
                <term xml:lang="en">PCSK9</term>
              </keywords>
              <classCode scheme="halDomain" n="sdv.bdd.eo">Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis</classCode>
              <classCode scheme="halDomain" n="sdv.bc.bc">Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]</classCode>
              <classCode scheme="halDomain" n="sdv.mhep.csc">Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system</classCode>
              <classCode scheme="halDomain" n="sdv.mhep.heg">Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology</classCode>
              <classCode scheme="halDomain" n="sdv.bio">Life Sciences [q-bio]/Biotechnology</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halOldTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">
              <p>Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. We aimed to validate urine-sample-derived human induced pluripotent stem cells (UhiPSCs) as an appropriate tool to model PCSK9-mediated ADH and FHBL. To achieve our goal, urine-sample-derived somatic cells were reprogrammed into hiPSCs by using episomal vectors. UhiPSC were efficiently differentiated into hepatocyte-like cells (HLCs). Compared to control cells, cells originally derived from an individual with ADH (HLC-S127R) secreted less PCSK9 in the media (−38.5%; P=0.038) and had a 71% decrease (P&lt;0.001) of low-density lipoprotein (LDL) uptake, whereas cells originally derived from an individual with FHBL (HLC-R104C/V114A) displayed a strong decrease in PCSK9 secretion (−89.7%; P&lt;0.001) and had a 106% increase (P=0.0104) of LDL uptake. Pravastatin treatment significantly enhanced LDL receptor (LDLR) and PCSK9 mRNA gene expression, as well as PCSK9 secretion and LDL uptake in both control and S127R HLCs. Pravastatin treatment of multiple clones led to an average increase of LDL uptake of 2.19±0.77-fold in HLC-S127R compared to 1.38±0.49 fold in control HLCs (P&lt;0.01), in line with the good response to statin treatment of individuals carrying the S127R mutation (mean LDL cholesterol reduction=60.4%, n=5). In conclusion, urine samples provide an attractive and convenient source of somatic cells for reprogramming and hepatocyte differentiation, but also a powerful tool to further decipher PCSK9 mutations and function.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <org type="laboratory" xml:id="struct-182196" status="OLD">
          <idno type="IdRef">190708026</idno>
          <idno type="RNSR">201220396X</idno>
          <orgName>ITX - unité de recherche de l'institut du thorax</orgName>
          <orgName type="acronym">ITX</orgName>
          <date type="start">2012-01-01</date>
          <date type="end">2021-12-31</date>
          <desc>
            <address>
              <addrLine>8 quai Moncousu - BP 70721 - 44007 Nantes Cedex 1</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.umr1087.univ-nantes.fr/</ref>
          </desc>
          <listRelation>
            <relation name="U1087" active="#struct-303623" type="direct"/>
            <relation name="UMR6291" active="#struct-441569" type="direct"/>
            <relation active="#struct-531638" type="direct"/>
            <relation active="#struct-93263" type="indirect"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-303623" status="VALID">
          <idno type="IdRef">026388278</idno>
          <idno type="ROR">https://ror.org/02vjkv261</idno>
          <orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
          <orgName type="acronym">INSERM</orgName>
          <desc>
            <address>
              <addrLine>101, rue de Tolbiac, 75013 Paris</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inserm.fr</ref>
          </desc>
        </org>
        <org type="regroupinstitution" xml:id="struct-441569" status="VALID">
          <idno type="IdRef">02636817X</idno>
          <idno type="ISNI">0000000122597504</idno>
          <idno type="ROR">https://ror.org/02feahw73</idno>
          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.cnrs.fr/</ref>
          </desc>
        </org>
        <org type="regrouplaboratory" xml:id="struct-531638" status="OLD">
          <idno type="IdRef">076954927</idno>
          <orgName>Université de Nantes - UFR de Médecine et des Techniques Médicales</orgName>
          <orgName type="acronym">UFR MEDECINE</orgName>
          <date type="end">2021-12-31</date>
          <desc>
            <address>
              <addrLine>1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.medecine.univ-nantes.fr</ref>
          </desc>
          <listRelation>
            <relation active="#struct-93263" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-93263" status="OLD">
          <idno type="IdRef">026403447</idno>
          <idno type="ROR">https://ror.org/03gnr7b55</idno>
          <orgName>Université de Nantes</orgName>
          <orgName type="acronym">UN</orgName>
          <date type="end">2021-12-31</date>
          <desc>
            <address>
              <addrLine>1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.univ-nantes.fr/</ref>
          </desc>
        </org>
      </listOrg>
      <listOrg type="projects">
        <org type="europeanProject" xml:id="projeurop-92449" status="VALID">
          <idno type="number">277188</idno>
          <idno type="program">FP7-PEOPLE-2010-RG</idno>
          <idno type="call">FP7-PEOPLE-2010-RG</idno>
          <orgName>IPSMILD</orgName>
          <desc>HUMAN INDUCED PLURIPOTENT STEM CELLS AS A MODEL TO STUDY METABOLIC INHERITED LIVER DISEASES</desc>
          <date type="start">2011-01-12</date>
          <date type="end">2014-11-30</date>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>