Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms.

TitleSingle nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms.
Publication TypeJournal Article
Year of Publication2022
AuthorsZhang, Z, Zamojski, M, Smith, GR, Willis, TL, Yianni, V, Mendelev, N, Pincas, H, Seenarine, N, Amper, MAnne S, Vasoya, M, Cheng, WSze, Zaslavsky, E, Nair, VD, Turgeon, JL, Bernard, DJ, Troyanskaya, OG, Andoniadou, CL, Sealfon, SC, Ruf-Zamojski, F
JournalCell Rep
Volume38
Issue10
Pagination110467
Date Published2022 03 08
ISSN2211-1247
KeywordsAged, Child, Chromatin, Chromatin Immunoprecipitation Sequencing, Female, Humans, Male, Stem Cells, Transcription Factors, Transcriptome
Abstract

<p>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.</p>

DOI10.1016/j.celrep.2022.110467
Alternate JournalCell Rep
PubMed ID35263594
PubMed Central IDPMC8957708
Grant ListMR/T012153/1 / MRC_ / Medical Research Council / United Kingdom
R01 DK046943 / DK / NIDDK NIH HHS / United States
R01 GM071966 / GM / NIGMS NIH HHS / United States
R56 DK046943 / DK / NIDDK NIH HHS / United States