Single nucleus multi-omics regulatory landscape of the murine pituitary

Frederique Ruf-Zamojski, Zidong Zhang, Michel Zamojski, Gregory R. Smith, Natalia Mendelev, Hanqing Liu, German Nudelman, Mika Moriwaki, Hanna Pincas, Rosa Gomez Castanon, Venugopalan D. Nair, Nitish Seenarine, Mary Anne S. Amper, Xiang Zhou, Luisina Ongaro, Chirine Toufaily, Gauthier Schang, Joseph R. Nery, Anna Bartlett, Andrew AldridgeNimisha Jain, Gwen V. Childs, Olga G. Troyanskaya, Joseph R. Ecker, Judith L. Turgeon, Corrine K. Welt, Daniel J. Bernard, Stuart C. Sealfon

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number2677
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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