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

doi:10.1016/j.celrep.2022.110467

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

Princeton University

Research output: Contribution to journal › Article › peer-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 language	American English
Article number	110467
Journal	Cell Reports
Volume	38
Issue number	10
DOIs	https://doi.org/10.1016/j.celrep.2022.110467
State	Published - Mar 8 2022

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Keywords

chromatin accessibility
multiomics
pituitary
single nucleus analysis
stem cells
transcriptome

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10.1016/j.celrep.2022.110467

Cite this

Zhang, Z., Zamojski, M., Smith, G. R., Willis, T. L., Yianni, V., Mendelev, N., Pincas, H., Seenarine, N., Amper, M. A. S., Vasoya, M., Cheng, W. S., Zaslavsky, E., Nair, V. D., Turgeon, J. L., Bernard, D. J., Troyanskaya, O. G., Andoniadou, C. L., Sealfon, S. C., & Ruf-Zamojski, F. (2022). Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms. Cell Reports, 38(10), Article 110467. https://doi.org/10.1016/j.celrep.2022.110467

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title = "Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms",

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",

author = "Zidong Zhang and Michel Zamojski and Smith, {Gregory R.} and Willis, {Thea L.} and Val Yianni and Natalia Mendelev and Hanna Pincas and Nitish Seenarine and Amper, {Mary Anne S.} and Mital Vasoya and Cheng, {Wan Sze} and Elena Zaslavsky and Nair, {Venugopalan D.} and Turgeon, {Judith L.} and Bernard, {Daniel J.} and Troyanskaya, {Olga G.} and Andoniadou, {Cynthia L.} and Sealfon, {Stuart C.} and Frederique Ruf-Zamojski",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = mar,

day = "8",

doi = "10.1016/j.celrep.2022.110467",

language = "American English",

volume = "38",

journal = "Cell Reports",

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Zhang, Z, Zamojski, M, Smith, GR, Willis, TL, Yianni, V, Mendelev, N, Pincas, H, Seenarine, N, Amper, MAS, Vasoya, M, Cheng, WS, Zaslavsky, E, Nair, VD, Turgeon, JL, Bernard, DJ, Troyanskaya, OG, Andoniadou, CL, Sealfon, SC & Ruf-Zamojski, F 2022, 'Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms', Cell Reports, vol. 38, no. 10, 110467. https://doi.org/10.1016/j.celrep.2022.110467

TY - JOUR

T1 - Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms

AU - Zhang, Zidong

AU - Zamojski, Michel

AU - Smith, Gregory R.

AU - Willis, Thea L.

AU - Yianni, Val

AU - Mendelev, Natalia

AU - Pincas, Hanna

AU - Seenarine, Nitish

AU - Amper, Mary Anne S.

AU - Vasoya, Mital

AU - Cheng, Wan Sze

AU - Zaslavsky, Elena

AU - Nair, Venugopalan D.

AU - Turgeon, Judith L.

AU - Bernard, Daniel J.

AU - Troyanskaya, Olga G.

AU - Andoniadou, Cynthia L.

AU - Sealfon, Stuart C.

AU - Ruf-Zamojski, Frederique

PY - 2022/3/8

Y1 - 2022/3/8

N2 - 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.

AB - 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.

KW - chromatin accessibility

KW - multiomics

KW - pituitary

KW - single nucleus analysis

KW - stem cells

KW - transcriptome

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DO - 10.1016/j.celrep.2022.110467

M3 - Article

C2 - 35263594

SN - 2211-1247

VL - 38

JO - Cell Reports

JF - Cell Reports

IS - 10

M1 - 110467

ER -

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

Abstract

ASJC Scopus subject areas

Keywords

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