Article (Scientific journals)
Single‑nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell‑type‑specific gene regulatory variation
Gui, Yujuan; Grzyb, Kamil; Thomas, Melanie et al.
2021In Epigenetics and Chromatin
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Keywords :
Single-nuclei ATAC-seq; Genetic variation; Midbrain
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Gui, Yujuan;  University of Luxembourg > Department of Life Sciences and Medicine
Grzyb, Kamil ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Thomas, Melanie ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology
Ohnmacht, Jochen ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Garcia, Pierre  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology
Buttini, Manuel ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology
Skupin, Alexander  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Integrative Cell Signalling
Sauter, Thomas ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Sinkkonen, Lasse  ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
External co-authors :
no
Language :
English
Title :
Single‑nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell‑type‑specific gene regulatory variation
Publication date :
09 September 2021
Journal title :
Epigenetics and Chromatin
ISSN :
1756-8935
Publisher :
BioMed Central, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
FnR Project :
FNR10406131 - Identifying Novel Genetic And Epigenetic Modulators Of Dopaminergic Neuron Structure And Function., 2015 (01/05/2016-30/04/2019) - Manuel Buttini
Funders :
Luxembourg National Research Fund, Fondation du Pélican de Mie et Pierre Hippert-Faber, Luxembourg Rotary Foundation
Available on ORBilu :
since 13 October 2021

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