{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li H"],"funding":["BLRD VA","U.S. Department of Health &amp; Human Services | NIH | National Institute of Neurological Disorders and Stroke","NINDS NIH HHS","U.S. Department of Veterans Affairs","New York State Stem Cell Science"],"pagination":["4407-4418"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9684358"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(11)"],"pubmed_abstract":["The degeneration of nigral (A9) dopaminergic (DA) neurons causes motor symptoms in Parkinson's disease (PD). We use small-molecule compounds to direct the differentiation of human induced pluripotent stem cells (iPSCs) to A9 DA neurons that share many important properties with their in vivo counterparts. The method generates a large percentage of TH<sup>+</sup> neurons that express appropriate A9 markers, such as GIRK2 and ALDH1A1, but mostly not the A10 marker CALBINDIN. Functionally, they exhibit autonomous pacemaking based on L-type voltage-dependent Ca<sup>2+</sup> channels and show autoreceptor-dependent regulation of dopamine release. When transplanted in the striatum of 6-OHDA-lesioned athymic rats, the human A9 DA neurons manifest robust survival and axon outgrowth, and ameliorate motor deficits in the rat PD model. The ability to generate patient-specific A9 DA autonomous pacemakers will significantly improve PD research and facilitate the development of disease-modifying therapies."],"journal":["Molecular psychiatry"],"pubmed_title":["Generation of human A9 dopaminergic pacemakers from induced pluripotent stem cells."],"pmcid":["PMC9684358"],"funding_grant_id":["R56 NS102148","I01 BX003831","C30290GG","R01 NS102148","NS102148","NS113763","R01 NS113763","BX003831"],"pubmed_authors":["Li H","Yan Z","Feng J","Jiang H","Li L"],"additional_accession":[]},"is_claimable":false,"name":"Generation of human A9 dopaminergic pacemakers from induced pluripotent stem cells.","description":"The degeneration of nigral (A9) dopaminergic (DA) neurons causes motor symptoms in Parkinson's disease (PD). We use small-molecule compounds to direct the differentiation of human induced pluripotent stem cells (iPSCs) to A9 DA neurons that share many important properties with their in vivo counterparts. The method generates a large percentage of TH<sup>+</sup> neurons that express appropriate A9 markers, such as GIRK2 and ALDH1A1, but mostly not the A10 marker CALBINDIN. Functionally, they exhibit autonomous pacemaking based on L-type voltage-dependent Ca<sup>2+</sup> channels and show autoreceptor-dependent regulation of dopamine release. When transplanted in the striatum of 6-OHDA-lesioned athymic rats, the human A9 DA neurons manifest robust survival and axon outgrowth, and ameliorate motor deficits in the rat PD model. The ability to generate patient-specific A9 DA autonomous pacemakers will significantly improve PD research and facilitate the development of disease-modifying therapies.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-05T11:28:00.557Z","creation":"2025-04-05T11:28:00.557Z"},"accession":"S-EPMC9684358","cross_references":{"pubmed":["35610351"],"doi":["10.1038/s41380-022-01628-1"]}}