학술논문
Single nucleus multi-omics regulatory landscape of the murine pituitary.
Document Type
Academic Journal
Author
Ruf-Zamojski F; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA. frederique.ruf-zamojski@mssm.edu.; Zhang Z; Lewis-Sigler Institute for Integrative Genomics, and Graduate Program in Quantitative and Computational Biology, Princeton University, Princeton, NJ, USA.; Zamojski M; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.; Smith GR; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.; Mendelev N; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.; Liu H; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Nudelman G; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.; Moriwaki M; Division of Endocrinology and Metabolism, University of Utah, Salt Lake City, UT, USA.; Pincas H; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.; Castanon RG; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Nair VD; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.; Seenarine N; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.; Amper MAS; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.; Zhou X; Dept. of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.; Ongaro L; Dept. of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.; Toufaily C; Dept. of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.; Schang G; Dept. of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.; Nery JR; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Bartlett A; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Aldridge A; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Jain N; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.; Childs GV; University of Arkansas for Medical Sciences, Little Rock, AR, USA.; Troyanskaya OG; Lewis-Sigler Institute for Integrative Genomics, and Graduate Program in Quantitative and Computational Biology, Princeton University, Princeton, NJ, USA.; Department of Computer Science, Princeton University, Princeton, NJ, USA.; Flatiron Institute, Simons Foundation, New York, NY, USA.; Ecker JR; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Turgeon JL; Department of Internal Medicine, University of California, Davis, CA, USA.; Welt CK; Division of Endocrinology and Metabolism, University of Utah, Salt Lake City, UT, USA.; Bernard DJ; Dept. of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.; Sealfon SC; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA. stuart.sealfon@mssm.edu.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
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.