Integrated single-cell transcriptomics and epigenomics reveals strong germinal center-associated etiology of autoimmune risk loci.
Autoimmunity
/ immunology
Cell Differentiation
/ immunology
Epigenomics
Germinal Center
/ immunology
Homeodomain Proteins
/ genetics
Humans
Interleukins
/ genetics
Palatine Tonsil
/ immunology
Sequence Analysis, RNA
Single-Cell Analysis
Trans-Activators
/ genetics
Transcription Factors
/ genetics
Transcriptome
Journal
Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624
Informations de publication
Date de publication:
15 Oct 2021
15 Oct 2021
Historique:
entrez:
8
10
2021
pubmed:
9
10
2021
medline:
8
3
2022
Statut:
ppublish
Résumé
The germinal center (GC) response is critical for both effective adaptive immunity and establishing peripheral tolerance by limiting autoreactive B cells. Dysfunction in these processes can lead to defective immune responses to infection or contribute to autoimmune disease. To understand the gene regulatory principles underlying the GC response, we generated a single-cell transcriptomic and epigenomic atlas of the human tonsil, a widely studied and representative lymphoid tissue. We characterize diverse immune cell subsets and build a trajectory of dynamic gene expression and transcription factor activity during B cell activation, GC formation, and plasma cell differentiation. We subsequently leverage cell type–specific transcriptomic and epigenomic maps to interpret potential regulatory impact of genetic variants implicated in autoimmunity, revealing that many exhibit their greatest regulatory potential in GC-associated cellular populations. These included gene loci linked with known roles in GC biology (
Identifiants
pubmed: 34623901
doi: 10.1126/sciimmunol.abh3768
pmc: PMC8859880
mid: NIHMS1775292
doi:
Substances chimiques
HHEX protein, human
0
Homeodomain Proteins
0
Interleukins
0
POU2AF1 protein, human
0
Trans-Activators
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabh3768Subventions
Organisme : NHGRI NIH HHS
ID : RM1 HG007735
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057266
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States
Organisme : NHGRI NIH HHS
ID : P50 HG007735
Pays : United States
Organisme : Wellcome Trust
ID : 213555/Z/18/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : P01 AI153559
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG009436
Pays : United States
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