{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:01:06Z","timestamp":1791165666019,"version":"4.1.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,4,27]]},"abstract":"<jats:p>Most lysosomal storage diseases (LSDs) are life-threatening genetic diseases. The pathogenesis of these diseases is poorly understood. Induced pluripotent stem (iPS) cell technology offers new opportunities for both mechanistic studies and development of stem cell\u2013 based therapies. Here we report the generation of disease-specific iPS cells from mouse models of Fabry disease, globoid cell leukodystrophy (GLD), and mucopolysaccharidosis VII (MPSVII). These mouse model\u2013derived iPS cells showed defects in disease-specific enzyme activities and significant accumulation of substrates for these enzymes. In the lineage-directed differentiation studies, Fabry-iPS and GLD-iPS cells were efficiently differentiated into disease-relevant cell types, such as cardiomyocytes and neural stem cells, which might be useful in mechanistic and therapeutic studies. Notably, MPSVII-iPS cells demonstrated a markedly impaired ability to form embryoid bodies (EBs) in vitro. MPSVII-EBs exibited elevated levels of hyaluronan and its receptor CD44, and markedly reduced expression levels of E-cadherin and cell-proliferating marker. Partial correction of enzyme deficiency in MSPVII-iPS cells led to improved EB formation and reversal of aberrant protein expression. These data indicate a potential mechanism for the partial lethality of MPSVII mice in utero, and suggest a possible abnormality of embryonic development in MPSVII patients. Thus, our study demonstrates the unique promise of iPS cells for studying the pathogenesis and treatment of LSDs.<\/jats:p>","DOI":"10.1073\/pnas.1002758107","type":"journal-article","created":{"date-parts":[[2010,4,12]],"date-time":"2010-04-12T23:45:08Z","timestamp":1271115908000},"page":"7886-7891","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":43,"title":["Induced pluripotent stem cells derived from mouse models of lysosomal storage disorders"],"prefix":"10.1073","volume":"107","author":[{"given":"Xing-Li","family":"Meng","sequence":"first","affiliation":[{"name":"Departments of aGene Therapy, and"},{"name":"Genetic Diseases and Genome Science, Jikei University School of Medicine, Tokyo 105-8461, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Song","family":"Shen","sequence":"additional","affiliation":[{"name":"Departments of aGene Therapy, and"},{"name":"Genetic Diseases and Genome Science, Jikei University School of Medicine, Tokyo 105-8461, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho","family":"Kawagoe","sequence":"additional","affiliation":[{"name":"Genetic Diseases and Genome Science, Jikei University School of Medicine, Tokyo 105-8461, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toya","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Departments of aGene Therapy, and"},{"name":"Genetic Diseases and Genome Science, Jikei University School of Medicine, Tokyo 105-8461, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roscoe O.","family":"Brady","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikatsu","family":"Eto","sequence":"additional","affiliation":[{"name":"Genetic Diseases and Genome Science, Jikei University School of Medicine, Tokyo 105-8461, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,4,12]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.3.249"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004399900075"},{"key":"e_1_3_3_3_2","first-page":"3733","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Desnick RJ","year":"2001","unstructured":"RJ Desnick, YA Ioannou, CM Eng, a-Galactosidase A deficiency: Fabry disease. 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