Single nucleus multi-omics regulatory landscape of the murine pituitary

• Published in: Nature communications Vol. 12; no. 1; pp. 2677 - 20
• Main Authors: Ruf-Zamojski, Frederique, Zhang, Zidong, Zamojski, Michel, Smith, Gregory R., Mendelev, Natalia, Liu, Hanqing, Nudelman, German, Moriwaki, Mika, Pincas, Hanna, Castanon, Rosa Gomez, Nair, Venugopalan D., Seenarine, Nitish, Amper, Mary Anne S., Zhou, Xiang, Ongaro, Luisina, Toufaily, Chirine, Schang, Gauthier, Nery, Joseph R., Bartlett, Anna, Aldridge, Andrew, Jain, Nimisha, Childs, Gwen V., Troyanskaya, Olga G., Ecker, Joseph R., Turgeon, Judith L., Welt, Corrine K., Bernard, Daniel J., Sealfon, Stuart C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-05-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 38; 38/39; 631/80; 692/163; Accessibility; Animals; Binding sites; Chromatin; Chromatin - genetics; Clustering; DNA Methylation; Female; Fertility; Follicle-stimulating hormone; Gene expression; Gene Expression Regulation; Gene Regulatory Networks; Humanities and Social Sciences; Male; Methylation; Mice; Mice, Inbred C57BL; Models, Genetic; multidisciplinary; Nuclei; Pituitary; Pituitary gland; Pituitary Gland - cytology; Pituitary Gland - metabolism; Polymorphism; Promoter Regions, Genetic - genetics; Regulatory mechanisms (biology); Regulon - genetics; Science; Science (multidisciplinary); Sex Factors; Transcriptome - genetics; Transcriptomes
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-22859-w

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.
The pituitary gland plays important roles in the regulation of key physiological functions. Here the authors provide a multiomics atlas including transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from mouse pituitaries.