@article{ac2acb85d51d42499fba07d77150943b,
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 = "Funding Information: This work was supported by funding from the National Institutes of Health (NIH) Grant DK46943(S.C.S.), Grant R01GM071966 (O.G.T.), Medical Research Council (MRC) Grant MR/T012153/1 (C.L.A.), and Canadian Institutes of Health Research Project Grants PJT-162343 and -169184 (D.J.B.). T.L.W. was funded by King's College London as part of the ?Cell Therapies and Regenerative Medicine? Four-Year Welcome Trust PhD Training Program. We acknowledge the New York Genome Center for sequencing. Human tissue was obtained from the NIH NeuroBioBank. This work was supported in part through the computational and data resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Z.Z. M.Z. G.R.S. V.Y. and O.G.T. contributed analytic tools and analyzed data; T.L.W. contributed analytic tools, analyzed data, and performed research; N.M. V.D.N. N.S. M.A.A. and M.V. performed research; H.P. drafted the manuscript; W.C. M.Z. and E.Z. established the quality control pipeline; S.C.S. designed the study, analyzed, interpreted data, and drafted the manuscript; C.L.A. J.L.T. and D.J.B. analyzed, interpreted data, and drafted the manuscript; F.R.Z. designed the study, performed research, analyzed and interpreted data, and drafted the manuscript. All authors edited the manuscript and approved its final version. The authors declare no competing interests. Funding Information: This work was supported by funding from the National Institutes of Health (NIH) Grant DK46943 (S.C.S.), Grant R01GM071966 (O.G.T.), Medical Research Council (MRC) Grant MR/T012153/1 (C.L.A.), and Canadian Institutes of Health Research Project Grants PJT-162343 and - 169184 (D.J.B.). T.L.W. was funded by King{\textquoteright}s College London as part of the “Cell Therapies and Regenerative Medicine” Four-Year Welcome Trust PhD Training Program. We acknowledge the New York Genome Center for sequencing. Human tissue was obtained from the NIH NeuroBioBank. This work was supported in part through the computational and data resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai . Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = mar,
day = "8",
doi = "10.1016/j.celrep.2022.110467",
language = "English",
volume = "38",
pages = "110467",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier BV",
number = "10",
}