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 Aldridge, Nimisha Jain, Gwen V. Childs, Olga G. Troyanskaya, Joseph R. Ecker, Judith L. Turgeon, Corrine K. Welt, Daniel J. Bernard and Stuart C. Sealfon ()
Additional contact information
Frederique Ruf-Zamojski: Icahn School of Medicine at Mount Sinai (ISMMS)
Zidong Zhang: Princeton University
Michel Zamojski: Icahn School of Medicine at Mount Sinai (ISMMS)
Gregory R. Smith: Icahn School of Medicine at Mount Sinai (ISMMS)
Natalia Mendelev: Icahn School of Medicine at Mount Sinai (ISMMS)
Hanqing Liu: The Salk Institute for Biological Studies
German Nudelman: Icahn School of Medicine at Mount Sinai (ISMMS)
Mika Moriwaki: University of Utah
Hanna Pincas: Icahn School of Medicine at Mount Sinai (ISMMS)
Rosa Gomez Castanon: The Salk Institute for Biological Studies
Venugopalan D. Nair: Icahn School of Medicine at Mount Sinai (ISMMS)
Nitish Seenarine: Icahn School of Medicine at Mount Sinai (ISMMS)
Mary Anne S. Amper: Icahn School of Medicine at Mount Sinai (ISMMS)
Xiang Zhou: McGill University
Luisina Ongaro: McGill University
Chirine Toufaily: McGill University
Gauthier Schang: McGill University
Joseph R. Nery: The Salk Institute for Biological Studies
Anna Bartlett: The Salk Institute for Biological Studies
Andrew Aldridge: The Salk Institute for Biological Studies
Nimisha Jain: Icahn School of Medicine at Mount Sinai (ISMMS)
Gwen V. Childs: University of Arkansas for Medical Sciences
Olga G. Troyanskaya: Princeton University
Joseph R. Ecker: The Salk Institute for Biological Studies
Judith L. Turgeon: University of California
Corrine K. Welt: University of Utah
Daniel J. Bernard: McGill University
Stuart C. Sealfon: Icahn School of Medicine at Mount Sinai (ISMMS)

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22859-w

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