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Alliance"],"accepted":{"date-parts":[[2024,3,14]]},"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:p>\n                    Glomerular filtration relies on the type IV collagen (ColIV) network of the glomerular basement membrane, namely, in the triple helical molecules containing the \u03b13, \u03b14, and \u03b15 chains of ColIV. Loss of function mutations in the genes encoding these chains (\n                    <jats:italic>Col4a3<\/jats:italic>\n                    ,\n                    <jats:italic>Col4a4<\/jats:italic>\n                    , and\n                    <jats:italic>Col4a5<\/jats:italic>\n                    ) is associated with the loss of renal function observed in Alport syndrome (AS). Precise understanding of the cellular basis for the patho-mechanism remains unknown and a specific therapy for this disease does not currently exist. Here, we generated a novel allele for the conditional deletion of\n                    <jats:italic>Col4a3<\/jats:italic>\n                    in different glomerular cell types in mice. We found that podocytes specifically generate \u03b13 chains in the developing glomerular basement membrane, and that its absence is sufficient to impair glomerular filtration as seen in AS. Next, we show that horizontal gene transfer, enhanced by TGF\u03b21 and using allogenic bone marrow\u2013derived mesenchymal stem cells and induced pluripotent stem cells, rescues\n                    <jats:italic>Col4a3<\/jats:italic>\n                    expression and revive kidney function in Col4a3-deficient AS mice. Our proof-of-concept study supports that horizontal gene transfer such as cell fusion enables cell-based therapy in Alport syndrome.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202402664","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T13:55:12Z","timestamp":1711979712000},"page":"e202402664","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic reprogramming with stem cells regenerates glomerular epithelial podocytes in Alport syndrome"],"prefix":"10.26508","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8514-8551","authenticated-orcid":true,"given":"Valerie S","family":"LeBleu","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"},{"name":"Northwestern University Feinberg School of Medicine and Kellogg School of Management, Chicago, IL, USA"},{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Baylor College of Medicine","place":[", Houston, TX, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Kanasaki","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7776-2896","authenticated-orcid":true,"given":"Sara","family":"Lovisa","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L","family":"Alge","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Baylor College of Medicine","place":[", Houston, TX, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiha","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqi","family":"Teng","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behzad","family":"Gerami-Naini","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-6887","authenticated-orcid":true,"given":"Noritoshi","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3584-4516","authenticated-orcid":true,"given":"Ignacio","family":"Revuelta","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Grau","sequence":"additional","affiliation":[{"name":"Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany"},{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1718-7687","authenticated-orcid":true,"given":"Jonathan P","family":"Sleeman","sequence":"additional","affiliation":[{"name":"Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany"},{"name":"Karlsruhe Institute of Technology (IBCS-BIP), Karlsruhe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangadhar","family":"Taduri","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akane","family":"Kizu","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Rafii","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Ansary Stem Cell Institute, Weill Cornell Medical College, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Hochedlinger","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, MA, USA"},{"name":"Harvard Stem Cell Institute, Boston, MA, 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