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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number110467
JournalCell Reports
Volume38
Issue number10
DOIs
StatePublished - Mar 8 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

  • chromatin accessibility
  • multiomics
  • pituitary
  • single nucleus analysis
  • stem cells
  • transcriptome

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