{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:04:22Z","timestamp":1789524262890,"version":"build-2803163510"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,1,3]]},"abstract":"<jats:p>\n                    Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the gene coding for FIBRILLIN-1 (FBN1), an extracellular matrix protein. MFS is inherited as an autosomal dominant trait and displays major manifestations in the ocular, skeletal, and cardiovascular systems. Here we report molecular and phenotypic profiles of skeletogenesis in tissues differentiated from human embryonic stem cells and induced pluripotent stem cells that carry a heritable mutation in\n                    <jats:italic>FBN1<\/jats:italic>\n                    . We demonstrate that, as a biological consequence of the activation of TGF-\u03b2 signaling, osteogenic differentiation of embryonic stem cells with a\n                    <jats:italic>FBN1<\/jats:italic>\n                    mutation is inhibited; osteogenesis is rescued by inhibition of TGF-\u03b2 signaling. In contrast, chondrogenesis is not perturbated and occurs in a TGF-\u03b2 cell-autonomous fashion. Importantly, skeletal phenotypes observed in human embryonic stem cells carrying the monogenic\n                    <jats:italic>FBN1<\/jats:italic>\n                    mutation (MFS cells) are faithfully phenocopied by cells differentiated from induced pluripotent-stem cells derived independently from MFS patient fibroblasts. Results indicate a unique phenotype uncovered by examination of mutant pluripotent stem cells and further demonstrate the faithful alignment of phenotypes in differentiated cells obtained from both human embryonic stem cells and induced pluripotent-stem cells, providing complementary and powerful tools to gain further insights into human molecular pathogenesis, especially of MFS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1113442109","type":"journal-article","created":{"date-parts":[[2011,12,17]],"date-time":"2011-12-17T01:43:00Z","timestamp":1324086180000},"page":"215-220","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":63,"title":["Skeletogenic phenotype of human Marfan embryonic stem cells faithfully phenocopied by patient-specific induced-pluripotent stem cells"],"prefix":"10.1073","volume":"109","author":[{"given":"Natalina","family":"Quarto","sequence":"first","affiliation":[{"name":"Department of Surgery, Hagey 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