{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:52:49Z","timestamp":1753890769667,"version":"3.41.2"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\u03b1-Synuclein (\u03b1Syn) is a small, disordered protein that becomes aggregated in Lewy body diseases, such as Parkinson\u2019s disease (PD) and dementia with Lewy bodies (DLB). Human induced pluripotent stem cells (hiPSCs) potentially provide a tractable disease model to monitor early molecular changes associated with PD\/DLB. We and others have previously derived hiPSC lines from patients with duplication and triplication of the <jats:italic>SNCA<\/jats:italic> gene, encoding for \u03b1Syn. It is now recognised that to perform meaningful disease modelling with these hiPSC lines, it is critical to generate isogenic control cell lines that lack the disease causing mutations. In order to complement the existing and emerging hiPSC models for PD\/DLB, we have generated an allelic series of \u03b1Syn over-expressing hESC lines on the same isogenic background. An unresolved question is whether pluripotent stem cell lines, with elevated levels of \u03b1Syn, can undergo efficient differentiation into dopaminergic and cortical neurons to model PD and DLB, respectively. We took advantage of our isogenic collection of hESC lines to determine if increased expression of \u03b1Syn affects neural induction and neuronal differentiation. Clonal hESC lines with significantly different levels of \u03b1Syn expression proliferated normally and maintained expression of pluripotent markers, such as OCT4. All cell lines efficiently produced PAX6<jats:sup>+<\/jats:sup> neuroectoderm and there was no correlation between \u03b1Syn expression and neural induction efficiency. Finally, global transcriptomic analysis of cortical differentiation of hESC lines with low or high levels of \u03b1Syn expression demonstrated robust and similar induction of cortical neuronal expression profiles. Gene expression differences observed were unrelated to neural induction and neuronal differentiation. We conclude that elevated expression of \u03b1Syn in human pluripotent stem cells does not adversely affect their neuronal differentiation potential and that collections of isogenic cell lines with differing levels of \u03b1Syn expression are valid and suitable models to investigate synucleinopathies.<\/jats:p>","DOI":"10.3389\/fcell.2022.898560","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T07:17:44Z","timestamp":1654067864000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["An Isogenic Collection of Pluripotent Stem Cell Lines With Elevated \u03b1-Synuclein Expression Validated for Neural Induction and Cortical Neuron Differentiation"],"prefix":"10.3389","volume":"10","author":[{"given":"Ammar","family":"Natalwala","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranya","family":"Behbehani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ratsuda","family":"Yapom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tilo","family":"Kunath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/s0896-6273(00)80886-7","article-title":"Mice Lacking \u03b1-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System","volume":"25","author":"Abeliovich","year":"2000","journal-title":"Neuron"},{"key":"B2","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.neurobiolaging.2008.11.001","article-title":"Absence of \u03b1-synuclein Affects Dopamine Metabolism and Synaptic Markers in the Striatum of Aging Mice","volume":"31","author":"Al-Wandi","year":"2010","journal-title":"Neurobiol. 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