Single nucleus multi-omics regulatory landscape of the murine pituitary.

TitleSingle nucleus multi-omics regulatory landscape of the murine pituitary.
Publication TypeJournal Article
Year of Publication2021
AuthorsRuf-Zamojski, F, Zhang, Z, Zamojski, M, Smith, GR, Mendelev, N, Liu, H, Nudelman, G, Moriwaki, M, Pincas, H, Castanon, RGomez, Nair, VD, Seenarine, N, Amper, MAnne S, Zhou, X, Ongaro, L, Toufaily, C, Schang, G, Nery, JR, Bartlett, A, Aldridge, A, Jain, N, Childs, GV, Troyanskaya, OG, Ecker, JR, Turgeon, JL, Welt, CK, Bernard, DJ, Sealfon, SC
JournalNat Commun
Volume12
Issue1
Pagination2677
Date Published2021 05 11
ISSN2041-1723
KeywordsAnimals, Chromatin, DNA Methylation, Female, Gene Expression Regulation, Gene Regulatory Networks, Male, Mice, Inbred C57BL, Models, Genetic, Pituitary Gland, Promoter Regions, Genetic, Regulon, Sex Factors, Transcriptome
Abstract

<p>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.</p>

DOI10.1038/s41467-021-22859-w
Alternate JournalNat Commun
PubMed ID33976139
PubMed Central IDPMC8113460
Grant ListR01 HD093461 / HD / NICHD NIH HHS / United States
R01 HD087057 / HD / NICHD NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
R01 DK046943 / DK / NIDDK NIH HHS / United States
R01 DK113776 / DK / NIDDK NIH HHS / United States
R01 HD065029 / HD / NICHD NIH HHS / United States
PJT-169184 / / CIHR / Canada
PJT-162343 / / CIHR / Canada