Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms. Author Zidong Zhang, Michel Zamojski, Gregory Smith, Thea Willis, Val Yianni, Natalia Mendelev, Hanna Pincas, Nitish Seenarine, Mary Amper, Mital Vasoya, Wan Cheng, Elena Zaslavsky, Venugopalan Nair, Judith Turgeon, Daniel Bernard, Olga Troyanskaya, Cynthia Andoniadou, Stuart Sealfon, Frederique Ruf-Zamojski Publication Year 2022 Type Journal Article 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. Keywords chromatin accessibility, multiomics, pituitary, single nucleus analysis, stem cells, transcriptome Journal Cell reports Volume 38 Issue 10 Pages 110467 Date Published 03/2022 ISSN Number 2211-1247 DOI 10.1016/j.celrep.2022.110467 Alternate Journal Cell Rep PMCID PMC8957708 PMID 35263594 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML