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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ruf-Zamojski, F; Zhang, Z; Zamojski, M; Smith, GR; Mendelev, N; Liu, H; Nudelman, G; Moriwaki, M; Pincas, H; Castanon, RG; Nair, VD; Seenarine, N; Amper, MAS; 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

Published Date

  • May 1, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 2677 -

PubMed ID

  • 33976139

Pubmed Central ID

  • PMC8113460

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-22859-w

Language

  • eng