Single nucleus multi-omics regulatory landscape of the murine pituitary
| Autor: | Stuart C. Sealfon, Judith L Turgeon, Hanqing Liu, Gwen V. Childs, Gregory R. Smith, Mika Moriwaki, Olga G. Troyanskaya, Michel Zamojski, Ecker, Amper Mas, Nery, Anna Bartlett, Zhou X, Gauthier Schang, Hanna Pincas, Nimisha Jain, Venugopalan D. Nair, Luisina Ongaro, Corrine K. Welt, Daniel J. Bernard, Rosa Castanon, Chirine Toufaily, Andrew Aldridge, Zinan Zhang, German Nudelman, Nitish Seenarine, Frederique Ruf-Zamojski, Natalia Mendelev |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cell type Science 1.1 Normal biological development and functioning Gene regulatory network General Physics and Astronomy Computational biology Biology Inbred C57BL Regulon General Biochemistry Genetics and Molecular Biology Transcriptome Promoter Regions 03 medical and health sciences Mice 0302 clinical medicine Sex Factors Genetic Models Underpinning research medicine Genetics Animals Gene Regulatory Networks Promoter Regions Genetic Transcription factor Regulation of gene expression Multidisciplinary Models Genetic Human Genome General Chemistry Methylation DNA Methylation Chromatin Mice Inbred C57BL medicine.anatomical_structure 030104 developmental biology Gene Expression Regulation Pituitary Gland DNA methylation Multi omics Female Nucleus 030217 neurology & neurosurgery |
| Zdroj: | Nature communications, vol 12, iss 1 Nature Communications, Vol 12, Iss 1, Pp 1-20 (2021) |
| ISSN: | 2041-1723 |
| Popis: | To provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from adult mouse pituitaries. Paired snRNAseq and snATACseq datasets from individual animals highlight a continuum between developmental epigenetically-encoded cell types and transcriptionally-determined transient cell states. Co-accessibility analysis-based identification of a putative Fshb cis-regulatory domain that overlaps the fertility-linked rs11031006 human polymorphism, followed by experimental validation illustrate the use of this resource for hypothesis generation. We also identify transcriptional and chromatin accessibility programs distinguishing each major cell type. Regulons, which are co-regulated gene sets sharing binding sites for a common transcription factor driver, recapitulate cell type clustering. We identify both cell type-specific and sex-specific regulons that are highly correlated with promoter accessibility, but not with methylation state, supporting the centrality of chromatin accessibility in shaping cell-defining transcriptional programs. The sn multi-omics atlas is accessible at snpituitaryatlas.princeton.edu. |
| Databáze: | OpenAIRE |
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