{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:53:48Z","timestamp":1790394828501,"version":"4.1.0"},"reference-count":13,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2016,7,30]],"date-time":"2016-07-30T00:00:00Z","timestamp":1469836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agenzia Spaziale Italiana (ASI) Progetto CoReA","award":["2013-084-R.0"],"award-info":[{"award-number":["2013-084-R.0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal Muscular Atrophy (SMA) is a neuromuscular disease caused by mutations in the Survival Motor Neuron 1 gene, resulting in very low levels of functional Survival of Motor Neuron (SMN) protein. SMA human induced Pluripotent Stem Cells (hiPSCs) represent a useful and valid model for the study of the disorder, as they provide in vitro the target cells. MicroRNAs (miRNAs) are often reported as playing a key role in regulating neuronal differentiation and fate specification. In this study SMA hiPSCs have been differentiated towards early motor neurons and their molecular and immunocytochemical profile were compared to those of wild type cells. Cell cycle proliferation was also evaluated by fluorescence-activated cell sorting (FACS). SMA hiPSCs showed an increased proliferation rate and also higher levels of stem cell markers. Moreover; when differentiated towards early motor neurons they expressed lower levels of NCAM and MN specific markers. The expression of miR-335-5p; already identified to control self-renewal or differentiation of mouse embryonic stem cells (mESCs); resulted to be reduced during the early steps of differentiation of SMA hiPSCs compared to wild type cells. These results suggest that we should speculate a role of this miRNA both in stemness characteristic and in differentiation efficiency of these cells.<\/jats:p>","DOI":"10.3390\/ijms17081231","type":"journal-article","created":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T03:47:39Z","timestamp":1470196059000},"page":"1231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["SMA Human iPSC-Derived Motor Neurons Show Perturbed Differentiation and Reduced miR-335-5p Expression"],"prefix":"10.3390","volume":"17","author":[{"given":"Michela","family":"Murdocca","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6467-8396","authenticated-orcid":false,"given":"Silvia","family":"Ciafr\u00e8","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Spitalieri","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Talarico","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-602X","authenticated-orcid":false,"given":"Giuseppe","family":"Novelli","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6227-4248","authenticated-orcid":false,"given":"Federica","family":"Sangiuolo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,7,30]]},"reference":[{"key":"ref_1","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":"ref_2","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/hmg\/6.8.1205","article-title":"The survival motor neuron protein in spinal muscular atrophy","volume":"6","author":"Coovert","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1006\/nbdi.1996.0010","article-title":"The neurobiology of childhood spinal muscular atrophy","volume":"3","author":"Crawford","year":"1996","journal-title":"Neurobiol. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1001\/archneurol.2010.89","article-title":"Stem cell model of spinal muscular atrophy","volume":"67","author":"Ebert","year":"2010","journal-title":"Arch. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.mcn.2014.12.005","article-title":"Pluripotent stem cell-based models of spinal muscular atrophy","volume":"64","author":"Frattini","year":"2015","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00441-014-1981-y","article-title":"The role of microRNAs in human stem cells, neuronal differentiation and subtype specification","volume":"359","author":"Stappert","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/stem.1315","article-title":"An OCT4-pRb axis, controlled by miR-335, integrates stem cell self-renewal and cell cycle control","volume":"31","author":"Schoeftner","year":"2013","journal-title":"Stem Cells"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18312","DOI":"10.3390\/ijms160818312","article-title":"A perturbed microRNA expression pattern characterizes embryonic neural stem cells derived from a severe mouse model of Spinal Muscular Atrophy (SMA)","volume":"16","author":"Luchetti","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0959-4388(00)00172-0","article-title":"Specification of neuronal fates in the ventral neural tube","volume":"11","author":"Briscoe","year":"2001","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0896-6273(01)80026-X","article-title":"Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity","volume":"23","author":"Arber","year":"1999","journal-title":"Neuron"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1089\/cell.2015.0003","article-title":"Generation of human induced pluripotent stem cells from extraembryonic tissues of fetuses affected by monogenic diseases","volume":"17","author":"Spitalieri","year":"2015","journal-title":"Cell. Reprogram."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/stem.2112","article-title":"Concise Review: Patient-derived stem cell research for monogenic disorders","volume":"34","author":"Qin","year":"2016","journal-title":"Stem Cells"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1523\/JNEUROSCI.0906-12.2013","article-title":"Accelerated high-yield generation of limb-innervating motor neurons from human stem cells","volume":"33","author":"Amoroso","year":"2013","journal-title":"J. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/8\/1231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:27:26Z","timestamp":1760210846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/8\/1231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,30]]},"references-count":13,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,8]]}},"alternative-id":["ijms17081231"],"URL":"https:\/\/doi.org\/10.3390\/ijms17081231","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,30]]}}}