{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:43:08Z","timestamp":1791085388666,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2011,11,16]],"date-time":"2011-11-16T00:00:00Z","timestamp":1321401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders in humans and is a common genetic cause of infant mortality. The disease is caused by loss of the survival of motoneuron (SMN) protein, resulting in the degeneration of alpha motoneurons in spinal cord and muscular atrophy in the limbs and trunk. One function of SMN involves RNA splicing. It is unclear why a deficiency in a housekeeping function such as RNA splicing causes profound effects only on motoneurons but not on other cell types. One difficulty in studying SMA is the scarcity of patient's samples. The discovery that somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) raises the intriguing possibility of modeling human diseases in vitro. We reported the establishment of five iPSC lines from the fibroblasts of a type 1 SMA patient. Neuronal cultures derived from these SMA iPSC lines exhibited a reduced capacity to form motoneurons and an abnormality in neurite outgrowth. Ectopic SMN expression in these iPSC lines restored normal motoneuron differentiation and rescued the phenotype of delayed neurite outgrowth. These results suggest that the observed abnormalities are indeed caused by SMN deficiency and not by iPSC clonal variability. Further characterization of the cellular and functional deficits in motoneurons derived from these iPSCs may accelerate the exploration of the underlying mechanisms of SMA pathogenesis.<\/jats:p>","DOI":"10.1002\/stem.749","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T20:28:42Z","timestamp":1317241722000},"page":"2090-2093","source":"Crossref","is-referenced-by-count":81,"title":["Brief Report: Phenotypic Rescue of Induced Pluripotent Stem Cell-Derived Motoneurons of a Spinal Muscular Atrophy Patient"],"prefix":"10.1093","volume":"29","author":[{"given":"Tammy","family":"Chang","sequence":"first","affiliation":[{"name":"Department of VirologyBeckman Research Institute, City of Hope, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of VirologyBeckman Research Institute, City of Hope, Duarte, California, USA"},{"name":"Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Tsark","sequence":"additional","affiliation":[{"name":"Transgenic Mice CoreBeckman Research Institute, City of Hope, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Bates","sequence":"additional","affiliation":[{"name":"Department of BiologyBeckman Research Institute, City of Hope, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Huang","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-Jang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiing-Kuan","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of VirologyBeckman Research Institute, City of Hope, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,11,16]]},"reference":[{"key":"2022011216054970000_bib1","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1016\/S0140-6736(08)60921-6","article-title":"Spinal muscular atrophy","volume":"371","author":"Lunn","year":"2008","journal-title":"Lancet"},{"key":"2022011216054970000_bib2","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.neuron.2005.12.001","article-title":"Spinal muscular atrophy: A deficiency in a ubiquitous protein; a motor neuron-specific disease","volume":"48","author":"Monani","year":"2005","journal-title":"Neuron"},{"key":"2022011216054970000_bib3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrn2670","article-title":"Spinal muscular atrophy: Why do low levels of survival motor neuron protein make motor neurons sick?","volume":"10","author":"Burghes","year":"2009","journal-title":"Nat Rev"},{"key":"2022011216054970000_bib4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"2022011216054970000_bib5","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1093\/hmg\/4.10.1927","article-title":"Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: Evidence of homozygous deletions of the SMN gene in unaffected individuals","volume":"4","author":"Hahnen","year":"1995","journal-title":"Hum Mol Genet"},{"key":"2022011216054970000_bib6","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"Lorson","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011216054970000_bib7","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/hmg\/8.7.1177","article-title":"A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2","volume":"8","author":"Monani","year":"1999","journal-title":"Hum Mol Genet"},{"key":"2022011216054970000_bib8","doi-asserted-by":"crossref","first-page":"3555","DOI":"10.1002\/j.1460-2075.1996.tb00725.x","article-title":"A novel nuclear structure containing the survival of motor neurons protein","volume":"15","author":"Liu","year":"1996","journal-title":"EMBO J"},{"key":"2022011216054970000_bib9","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.yexcr.2004.03.022","article-title":"The SMN complex","volume":"296","author":"Gubitz","year":"2004","journal-title":"Exp Cell Res"},{"key":"2022011216054970000_bib10","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.tcb.2004.03.010","article-title":"Why do cells need an assembly machine for RNA\u2013protein complexes?","volume":"14","author":"Yong","year":"2004","journal-title":"Trends Cell Biol"},{"key":"2022011216054970000_bib11","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1093\/hmg\/11.14.1605","article-title":"Survival motor neuron (SMN) protein: Role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development","volume":"11","author":"Fan","year":"2002","journal-title":"Hum Mol Genet"},{"key":"2022011216054970000_bib12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0002-9440(10)65578-2","article-title":"Cell-specific survival motor neuron gene expression during human development of the central nervous system: Implications for the pathogenesis of spinal muscular atrophy","volume":"153","author":"Tizzano","year":"1998","journal-title":"Am J Pathol"},{"key":"2022011216054970000_bib13","doi-asserted-by":"crossref","first-page":"6627","DOI":"10.1523\/JNEUROSCI.23-16-06627.2003","article-title":"Active transport of the survival motor neuron protein and the role of exon-7 in cytoplasmic localization","volume":"23","author":"Zhang","year":"2003","journal-title":"J Neurosci"},{"key":"2022011216054970000_bib14","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1083\/jcb.200304128","article-title":"Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons","volume":"163","author":"Rossoll","year":"2003","journal-title":"J Cell Biol"},{"key":"2022011216054970000_bib15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nature06534","article-title":"Reprogramming of human somatic cells to pluripotency with defined factors","volume":"451","author":"Park","year":"2008","journal-title":"Nature"},{"key":"2022011216054970000_bib16","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"2022011216054970000_bib17","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"2022011216054970000_bib18","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nature05944","article-title":"In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state","volume":"448","author":"Wernig","year":"2007","journal-title":"Nature"},{"key":"2022011216054970000_bib19","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced pluripotent stem cell lines derived from human somatic cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"2022011216054970000_bib20","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nature07677","article-title":"Induced pluripotent stem cells from a spinal muscular atrophy patient","volume":"457","author":"Ebert","year":"2009","journal-title":"Nature"},{"key":"2022011216054970000_bib21","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/s12015-010-9138-1","article-title":"Robust enhancement of neural differentiation from human ES and iPS cells regardless of their innate difference in differentiation propensity","volume":"6","author":"Kim","year":"2010","journal-title":"Stem Cell Rev"},{"key":"2022011216054970000_bib22","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1073\/pnas.0910012107","article-title":"Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency","volume":"107","author":"Hu","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011216054970000_bib23","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature09342","article-title":"Epigenetic memory in induced pluripotent stem cells","volume":"467","author":"Kim","year":"2010","journal-title":"Nature"},{"key":"2022011216054970000_bib24","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nbt1063","article-title":"Specification of motoneurons from human embryonic stem cells","volume":"23","author":"Li","year":"2005","journal-title":"Nat Biotechnol"},{"key":"2022011216054970000_bib25","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/hmg\/ddl482","article-title":"Stat5 constitutive activation rescues defects in spinal muscular atrophy","volume":"16","author":"Ting","year":"2007","journal-title":"Hum Mol Genet"}],"container-title":["Stem Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fstem.749","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/stem.749","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/stem.749","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/29\/12\/2090\/41966719\/stmcls_29_12_2090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/29\/12\/2090\/41966719\/stmcls_29_12_2090.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T03:11:13Z","timestamp":1642561873000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stmcls\/article\/29\/12\/2090-2093\/6419990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,16]]},"references-count":25,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2011,11,16]]},"published-print":{"date-parts":[[2011,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/stem.749","relation":{},"ISSN":["1066-5099","1549-4918"],"issn-type":[{"value":"1066-5099","type":"print"},{"value":"1549-4918","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,12,1]]},"published":{"date-parts":[[2011,11,16]]}}}