{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:26:54Z","timestamp":1760059614901,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Excellence at the Department of Translational Medicine (DIMET), Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["FG_19_2023","68155","2022CAWRK5"],"award-info":[{"award-number":["FG_19_2023","68155","2022CAWRK5"]}]},{"name":"DIG-ALS, AriSLA Foundation","award":["FG_19_2023","68155","2022CAWRK5"],"award-info":[{"award-number":["FG_19_2023","68155","2022CAWRK5"]}]},{"name":"CSP\u2014Compagnia San Paolo Trapezio","award":["FG_19_2023","68155","2022CAWRK5"],"award-info":[{"award-number":["FG_19_2023","68155","2022CAWRK5"]}]},{"name":"PRIN 2022","award":["FG_19_2023","68155","2022CAWRK5"],"award-info":[{"award-number":["FG_19_2023","68155","2022CAWRK5"]}]},{"name":"Bando per la Ricerca Roche 2024","award":["FG_19_2023","68155","2022CAWRK5"],"award-info":[{"award-number":["FG_19_2023","68155","2022CAWRK5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting motor neurons with a phenotypic and genetic heterogeneity and elusive molecular mechanisms. With the present pilot study, we investigated different genetic mutations (C9orf72, TARDBP, and KIF5A) associated with ALS by generating induced pluripotent stem cells (iPSCs) from peripheral blood of ALS patients and healthy donors. iPSCs showed the typical morphology, expressed stem cell markers both at RNA (OCT4, SOX2, KLF4, and c-Myc) and protein (Oct4, Sox2, SSEA3, and Tra1-60) levels. Moreover, embryoid bodies expressing the three germ-layer markers and neurospheres expressing neural progenitor markers were generated. Importantly, the transcriptomic profiles of iPSCs and neurospheres were analyzed to highlight the differences between ALS patients and healthy controls. Interestingly, the differentially expressed genes (DEGs) shared across all ALS iPSCs are linked to extracellular matrix, highlighting its importance in ALS progression. In contrast, ALS neurospheres displayed widespread deficits in neuronal pathways, although these DEGs were varied among patients, reflecting the disease\u2019s heterogeneity. Overall, we generated iPSC lines from ALS patients with diverse genetic backgrounds offering a tool for unravelling the intricate molecular landscape of ALS, paving the way for identifying key pathways implicated in pathogenesis and the disease\u2019s phenotypic variability.<\/jats:p>","DOI":"10.3390\/cells14130958","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T10:44:41Z","timestamp":1750761881000},"page":"958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Transcriptomic Differences in Induced Pluripotent Stem Cells and Neural Progenitors from Amyotrophic Lateral Sclerosis Patients Carrying Different Mutations: A Pilot Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Chiara","family":"Sgromo","sequence":"first","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0053-0098","authenticated-orcid":false,"given":"Martina","family":"Tosi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5738-213X","authenticated-orcid":false,"given":"Cristina","family":"Olgasi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-1880","authenticated-orcid":false,"given":"Fabiola","family":"De Marchi","sequence":"additional","affiliation":[{"name":"ALS Centre, Neurology Unit, Department of Translational Medicine, Maggiore della Carit\u00e0 Hospital, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-8335","authenticated-orcid":false,"given":"Francesco","family":"Favero","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"},{"name":"CAAD (Center on Autoimmune and Allergic Diseases), Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Venturin","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Piola","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5003-831X","authenticated-orcid":false,"given":"Alessia","family":"Cucci","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Corrado","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-9120","authenticated-orcid":false,"given":"Letizia","family":"Mazzini","sequence":"additional","affiliation":[{"name":"ALS Centre, Neurology Unit, Department of Translational Medicine, Maggiore della Carit\u00e0 Hospital, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"D\u2019Alfonso","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"},{"name":"CAAD (Center on Autoimmune and Allergic Diseases), Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Follenzi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi del Piemonte Orientale, 28100 Novara, Italy"},{"name":"Dipartimento Attivit\u00e0 Integrate Ricerca Innovazione, Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e C. Arrigo, 15122 Alessandria, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic Lateral Sclerosis","volume":"400","author":"Feldman","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1474-4422(21)00414-2","article-title":"Emerging Insights into the Complex Genetics and Pathophysiology of Amyotrophic Lateral Sclerosis","volume":"21","author":"Goutman","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/jnc.15255","article-title":"Cellular and Physiological Functions of C9ORF72 and Implications for ALS\/FTD","volume":"157","author":"Pang","year":"2021","journal-title":"J. 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