ArticleEpigenetics & chromatin2021
Single-nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell-type-specific gene regulatory variation.
Article in Epigenetics & chromatin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Article
- Iterative assay for transposase-accessible chromatin by sequencing to isolate functionally relevant neuronal subtypes.Science advances · 2024Article
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
- Normal and Pathological NRF2 Signalling in the Central Nervous System.Antioxidants (Basel, Switzerland) · 2022Review
- Allostery, and how to define and measure signal transduction.Biophysical chemistry · 2022Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCell 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.
resultsWe 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.
conclusionsOur 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.
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