Multiomics analysis identifies novel facilitators of human dopaminergic neuron differentiation [* Cross-Reference *]

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Borja Gomez Ramos; Jochen Ohnmacht; Nikola de Lange; Elena Valceschini; Aurélien Ginolhac; Marie Catillon; Daniele Ferrante; Aleksandar Raković; Rashi Halder; François Massart; Giuseppe Arena; Paul Antony; Silvia Bolognin; Christine Klein; Roland Krause; Marcel H. Schulz; Thomas Sauter; Rejko Krüger; Lasse Sinkkonen, 2026, "Multiomics analysis identifies novel facilitators of human dopaminergic neuron differentiation [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.HMHCYY, LIST Open Repository, V1
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Description
Midbrain dopaminergic neurons (mDANs) control voluntary movement, cognition, and reward behavior under physiological conditions and are implicated in human diseases such as Parkinson’s disease (PD). Many transcription factors (TFs) controlling human mDAN differentiation during development have been described, but much of the regulatory landscape remains undefined. Using a tyrosine hydroxylase (TH) human iPSC reporter line, we here generate time series transcriptomic and epigenomic profiles of purified mDANs during differentiation. Integrative analysis predicts novel regulators of mDAN differentiation and super-enhancers are used to identify key TFs. We find LBX1, NHLH1 and NR2F1/2 to promote mDAN differentiation and show that overexpression of either LBX1 or NHLH1 can also improve mDAN specification. A more detailed investigation of TF targets reveals that NHLH1 promotes the induction of neuronal miR-124, LBX1 regulates cholesterol biosynthesis, and NR2F1/2 controls neuronal activity. (2023-12-19)
***This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1038/s44319-023-00024-2 for the original and latest version of the publication*** (2026-07-01)
Subject Chemistry; Medicine, Health and Life Sciences
Keyword Dopaminergic, Transcription factor, Biology, Transcriptome, Tyrosine hydroxylase, Enhancer, Neuroscience, Computational biology, Dopamine, Genetics, Gene, Gene expression
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