Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity

Human dendritic cells (DCs) comprise subsets with distinct phenotypic and functional characteristics, but the transcriptional programs that dictate their identity remain elusive. Here, we analyze global chromatin accessibility profiles across resting and stimulated human DC subsets by means of the a...

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Autores principales: Leylek, Rebecca, Alcántara-Hernández, Marcela, Granja, Jeffrey M., Chavez, Michael, Perez, Kimberly, Diaz, Oscar R., Li, Rui, Satpathy, Ansuman T., Chang, Howard Y., Idoyaga, Juliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546547/
https://www.ncbi.nlm.nih.gov/pubmed/32966789
http://dx.doi.org/10.1016/j.celrep.2020.108180
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author Leylek, Rebecca
Alcántara-Hernández, Marcela
Granja, Jeffrey M.
Chavez, Michael
Perez, Kimberly
Diaz, Oscar R.
Li, Rui
Satpathy, Ansuman T.
Chang, Howard Y.
Idoyaga, Juliana
author_facet Leylek, Rebecca
Alcántara-Hernández, Marcela
Granja, Jeffrey M.
Chavez, Michael
Perez, Kimberly
Diaz, Oscar R.
Li, Rui
Satpathy, Ansuman T.
Chang, Howard Y.
Idoyaga, Juliana
author_sort Leylek, Rebecca
collection PubMed
description Human dendritic cells (DCs) comprise subsets with distinct phenotypic and functional characteristics, but the transcriptional programs that dictate their identity remain elusive. Here, we analyze global chromatin accessibility profiles across resting and stimulated human DC subsets by means of the assay for transposase-accessible chromatin using sequencing (ATAC-seq). We uncover specific regions of chromatin accessibility for each subset and transcriptional regulators of DC function. By comparing plasmacytoid DC responses to IFN-I-producing and non-IFN-I-producing conditions, we identify genetic programs related to their function. Finally, by intersecting chromatin accessibility with genome-wide association studies, we recognize DC subset-specific enrichment of heritability in autoimmune diseases. Our results unravel the basis of human DC subset heterogeneity and provide a framework for their analysis in disease pathogenesis.
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spelling pubmed-75465472020-10-09 Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity Leylek, Rebecca Alcántara-Hernández, Marcela Granja, Jeffrey M. Chavez, Michael Perez, Kimberly Diaz, Oscar R. Li, Rui Satpathy, Ansuman T. Chang, Howard Y. Idoyaga, Juliana Cell Rep Article Human dendritic cells (DCs) comprise subsets with distinct phenotypic and functional characteristics, but the transcriptional programs that dictate their identity remain elusive. Here, we analyze global chromatin accessibility profiles across resting and stimulated human DC subsets by means of the assay for transposase-accessible chromatin using sequencing (ATAC-seq). We uncover specific regions of chromatin accessibility for each subset and transcriptional regulators of DC function. By comparing plasmacytoid DC responses to IFN-I-producing and non-IFN-I-producing conditions, we identify genetic programs related to their function. Finally, by intersecting chromatin accessibility with genome-wide association studies, we recognize DC subset-specific enrichment of heritability in autoimmune diseases. Our results unravel the basis of human DC subset heterogeneity and provide a framework for their analysis in disease pathogenesis. 2020-09-22 /pmc/articles/PMC7546547/ /pubmed/32966789 http://dx.doi.org/10.1016/j.celrep.2020.108180 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Leylek, Rebecca
Alcántara-Hernández, Marcela
Granja, Jeffrey M.
Chavez, Michael
Perez, Kimberly
Diaz, Oscar R.
Li, Rui
Satpathy, Ansuman T.
Chang, Howard Y.
Idoyaga, Juliana
Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity
title Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity
title_full Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity
title_fullStr Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity
title_full_unstemmed Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity
title_short Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity
title_sort chromatin landscape underpinning human dendritic cell heterogeneity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546547/
https://www.ncbi.nlm.nih.gov/pubmed/32966789
http://dx.doi.org/10.1016/j.celrep.2020.108180
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