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Multiomics analysis identifies novel facilitators of human dopaminergic neuron differentiation.
Gomez Ramos, Borja; Ohnmacht, Jochen; de Lange, Nikola; Valceschini, Elena; Ginolhac, Aurélien; Catillon, Marie; Ferrante, Daniele; Rakovic, Aleksandar; Halder, Rashi; Massart, François; Arena, Giuseppe; Antony, Paul; Bolognin, Silvia; Klein, Christine; Krause, Roland; Schulz, Marcel H; Sauter, Thomas; Krüger, Rejko; Sinkkonen, Lasse.
Afiliación
  • Gomez Ramos B; Department of Life Sciences and Medicine (DLSM), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Ohnmacht J; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • de Lange N; Department of Life Sciences and Medicine (DLSM), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Valceschini E; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Ginolhac A; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Catillon M; Department of Life Sciences and Medicine (DLSM), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Ferrante D; Department of Life Sciences and Medicine (DLSM), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Rakovic A; Department of Life Sciences and Medicine (DLSM), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Halder R; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Massart F; Institute of Neurogenetics, University of Lübeck, 23538, Lübeck, Germany.
  • Arena G; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Antony P; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Bolognin S; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Klein C; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Krause R; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Schulz MH; Institute of Neurogenetics, University of Lübeck, 23538, Lübeck, Germany.
  • Sauter T; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Belvaux, Luxembourg.
  • Krüger R; Institute for Cardiovascular Regeneration, Goethe University, 60590, Frankfurt, Germany.
  • Sinkkonen L; German Centre for Cardiovascular Research, Partner site Rhein-Main, 60590, Frankfurt am Main, Germany.
EMBO Rep ; 25(1): 254-285, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38177910
ABSTRACT
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Madre Pluripotentes Inducidas / Neuronas Dopaminérgicas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2024 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Madre Pluripotentes Inducidas / Neuronas Dopaminérgicas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2024 Tipo del documento: Article