Reference : Single‑nuclei chromatin profiling of ventral midbrain reveals cell identity transcrip...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/48331
Single‑nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell‑type‑specific gene regulatory variation
English
Gui, Yujuan [University of Luxembourg > Department of Life Sciences and Medicine]
Grzyb, Kamil mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Thomas, Melanie mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology >]
Ohnmacht, Jochen mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
Garcia, Pierre mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology >]
Buttini, Manuel mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology >]
Skupin, Alexander mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Integrative Cell Signalling >]
Sauter, Thomas mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
Sinkkonen, Lasse mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
9-Sep-2021
Epigenetics and Chromatin
BioMed Central
Yes (verified by ORBilu)
International
1756-8935
United Kingdom
[en] Single-nuclei ATAC-seq ; Genetic variation ; Midbrain
[en] Background: Cell types in ventral midbrain are involved in diseases with variable genetic susceptibility, such as Parkinson’s disease and schizophrenia. Many genetic variants affect regulatory regions and alter gene expression in a cell-type-specific manner depending on the chromatin structure and accessibility.
Results: We report 20,658 single-nuclei chromatin accessibility profiles of ventral midbrain from two genetically and phenotypically distinct mouse strains. We distinguish ten cell types based on chromatin profiles and analysis of accessible regions controlling cell identity genes highlights cell-type-specific key transcription factors. Regulatory variation segregating the mouse strains manifests more on transcriptome than chromatin level. However, cell-type-level data reveals changes not captured at tissue level. To discover the scope and cell-type specificity of cis-acting variation in midbrain gene expression, we identify putative regulatory variants and show them to be enriched at differentially expressed loci. Finally, we find TCF7L2 to mediate trans-acting variation selectively in midbrain neurons.
Conclusions: Our data set provides an extensive resource to study gene regulation in mesencephalon and provides insights into control of cell identity in the midbrain and identifies cell-type-specific regulatory variation possibly underlying phenotypic and behavioural differences between mouse strains.
Luxembourg National Research Fund, Fondation du Pélican de Mie et Pierre Hippert-Faber, Luxembourg Rotary Foundation
Researchers
http://hdl.handle.net/10993/48331
10.1186/s13072-021-00418-3
FnR ; FNR10406131 > Manuel Buttini > DANeuroGEN > Identifying Novel Genetic And Epigenetic Modulators Of Dopaminergic Neuron Structure And Function. > 01/05/2016 > 30/04/2019 > 2015

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