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Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling

Akbari, Soheil; Sevinc, Gulben Gurhan; Ersoy, Nevin; Basak, Onur; Kaplan, Kubra; Sevinc, Kenan; Ozel, Erkin; Sengun, Berke; Enustun, Eray; Ozcimen, Burcu; Bagriyanik, Alper; Arslan, Nur; Onder, Tamer Tevfik; Erdal, Esra


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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/75351</identifier>
  <creators>
    <creator>
      <creatorName>Akbari, Soheil</creatorName>
      <givenName>Soheil</givenName>
      <familyName>Akbari</familyName>
    </creator>
    <creator>
      <creatorName>Sevinc, Gulben Gurhan</creatorName>
      <givenName>Gulben Gurhan</givenName>
      <familyName>Sevinc</familyName>
      <affiliation>Koc Univ, Fac Med, TR-34450 Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Ersoy, Nevin</creatorName>
      <givenName>Nevin</givenName>
      <familyName>Ersoy</familyName>
      <affiliation>Dokuz Eylul Univ, Hlth Sci Inst, Dept Histol &amp; Embryol, TR-35340 Izmir, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Basak, Onur</creatorName>
      <givenName>Onur</givenName>
      <familyName>Basak</familyName>
    </creator>
    <creator>
      <creatorName>Kaplan, Kubra</creatorName>
      <givenName>Kubra</givenName>
      <familyName>Kaplan</familyName>
    </creator>
    <creator>
      <creatorName>Sevinc, Kenan</creatorName>
      <givenName>Kenan</givenName>
      <familyName>Sevinc</familyName>
      <affiliation>Koc Univ, Fac Med, TR-34450 Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Ozel, Erkin</creatorName>
      <givenName>Erkin</givenName>
      <familyName>Ozel</familyName>
      <affiliation>Koc Univ, Fac Med, TR-34450 Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Sengun, Berke</creatorName>
      <givenName>Berke</givenName>
      <familyName>Sengun</familyName>
      <affiliation>Koc Univ, Fac Med, TR-34450 Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Enustun, Eray</creatorName>
      <givenName>Eray</givenName>
      <familyName>Enustun</familyName>
      <affiliation>Koc Univ, Fac Med, TR-34450 Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Ozcimen, Burcu</creatorName>
      <givenName>Burcu</givenName>
      <familyName>Ozcimen</familyName>
      <affiliation>Koc Univ, Fac Med, TR-34450 Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Bagriyanik, Alper</creatorName>
      <givenName>Alper</givenName>
      <familyName>Bagriyanik</familyName>
    </creator>
    <creator>
      <creatorName>Arslan, Nur</creatorName>
      <givenName>Nur</givenName>
      <familyName>Arslan</familyName>
    </creator>
    <creator>
      <creatorName>Onder, Tamer Tevfik</creatorName>
      <givenName>Tamer Tevfik</givenName>
      <familyName>Onder</familyName>
      <affiliation>Koc Univ, Fac Med, TR-34450 Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Erdal, Esra</creatorName>
      <givenName>Esra</givenName>
      <familyName>Erdal</familyName>
    </creator>
  </creators>
  <titles>
    <title>Robust, Long-Term Culture Of Endoderm-Derived Hepatic Organoids For Disease Modeling</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2019</publicationYear>
  <dates>
    <date dateType="Issued">2019-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/75351</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.stemcr.2019.08.007</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (&amp;gt;16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASST) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner.</description>
  </descriptions>
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