Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms
Zidong Zhang,
Michel Zamojski,
Gregory R. Smith,
Thea L. Willis,
Val Yianni,
Natalia Mendelev,
Hanna Pincas,
Nitish Seenarine,
Mary Anne S. Amper,
Mital Vasoya,
Wan Sze Cheng,
Elena Zaslavsky,
Venugopalan D. Nair,
Judith L. Turgeon,
Daniel J. Bernard,
Olga G. Troyanskaya,
Cynthia L. Andoniadou,
Stuart C. Sealfon,
Frederique Ruf-Zamojski
Affiliations
Zidong Zhang
Lewis-Sigler Institute for Integrative Genomics and Graduate Program in Quantitative and Computational Biology, Princeton University, Princeton, NJ, USA
Michel Zamojski
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Gregory R. Smith
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Thea L. Willis
Center for Craniofacial and Regenerative Biology, King's College London, London, UK
Val Yianni
Center for Craniofacial and Regenerative Biology, King's College London, London, UK
Natalia Mendelev
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Hanna Pincas
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Nitish Seenarine
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Mary Anne S. Amper
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Mital Vasoya
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Wan Sze Cheng
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Elena Zaslavsky
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Venugopalan D. Nair
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA
Judith L. Turgeon
Department of Internal Medicine, University of California, Davis, Davis, CA, USA
Daniel J. Bernard
Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada
Olga G. Troyanskaya
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
Cynthia L. Andoniadou
Center for Craniofacial and Regenerative Biology, King's College London, London, UK; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Corresponding author
Stuart C. Sealfon
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA; Corresponding author
Frederique Ruf-Zamojski
Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA; Corresponding author
Summary: Despite their importance in tissue homeostasis and renewal, human pituitary stem cells (PSCs) are incompletely characterized. We describe a human single nucleus RNA-seq and ATAC-seq resource from pediatric, adult, and aged postmortem pituitaries (snpituitaryatlas.princeton.edu) and characterize cell-type-specific gene expression and chromatin accessibility programs for all major pituitary cell lineages. We identify uncommitted PSCs, committing progenitor cells, and sex differences. Pseudotime trajectory analysis indicates that early-life PSCs are distinct from the other age groups. Linear modeling of same-cell multiome data identifies regulatory domain accessibility sites and transcription factors that are significantly associated with gene expression in PSCs compared with other cell types and within PSCs. We identify distinct deterministic mechanisms that contribute to heterogeneous marker expression within PSCs. These findings characterize human stem cell lineages and reveal diverse mechanisms regulating key PSC genes and cell type identity.
