Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms.
chromatin accessibility
multiomics
pituitary
single nucleus analysis
stem cells
transcriptome
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
08 03 2022
08 03 2022
Historique:
received:
16
07
2021
revised:
23
11
2021
accepted:
09
02
2022
entrez:
9
3
2022
pubmed:
10
3
2022
medline:
12
4
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35263594
pii: S2211-1247(22)00200-5
doi: 10.1016/j.celrep.2022.110467
pmc: PMC8957708
mid: NIHMS1787421
pii:
doi:
Substances chimiques
Chromatin
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110467Subventions
Organisme : Medical Research Council
ID : MR/T012153/1
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK046943
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM071966
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK046943
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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