Single-nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell-type-specific gene regulatory variation
| العنوان: | Single-nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell-type-specific gene regulatory variation |
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| المؤلفون: | Thomas Sauter, Mélanie H. Thomas, Kamil Grzyb, Manuel Buttini, Jochen Ohnmacht, Yujuan Gui, Pierre Garcia, Alexander Skupin, Lasse Sinkkonen |
| المصدر: | Epigenetics & Chromatin Epigenetics & Chromatin, Vol 14, Iss 1, Pp 1-20 (2021) |
| بيانات النشر: | BioMed Central, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cell type, QH426-470, Biology, Regulatory Sequences, Nucleic Acid, Midbrain, Transcriptome, Mice, Mesencephalon, Gene expression, Genetics, Animals, Genetic variation, Single-nuclei ATAC-seq, Molecular Biology, Gene, Transcription factor, Wnt signalling, Regulation of gene expression, Research, Chromatin, Mouse strains, Regulatory sequence, Cell-type identity, Transcription Factors |
| الوصف: | 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 ofcis-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 mediatetrans-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. |
| اللغة: | English |
| تدمد: | 1756-8935 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6693a26a97b1aa53b88bff0221f95fb2Test http://europepmc.org/articles/PMC8427957Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6693a26a97b1aa53b88bff0221f95fb2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17568935 |
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