GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE149622 Query DataSets for GSE149622
Status Public on Dec 14, 2020
Title Skin-resident innate lymphoid cells converge on a pathogenic effector state
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Tissue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of specific transcription factors and cytokines1. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in response to IL-23 signalling contributes to dermal inflammation in psoriasis. However, it is not known whether this response is initiated by pre-committed ILCs or by cell-state transitions. Here we show that the induction of psoriasis in mice by IL-23 or imiquimod reconfigures a spectrum of skin ILCs, which converge on a pathogenic ILC3-like state. Tissue-resident ILCs were necessary and sufficient, in the absence of circulatory ILCs, to drive pathology. Single-cell RNA-sequencing (scRNA-seq) profiles of skin ILCs along a time course of psoriatic inflammation formed a dense transcriptional continuum—even at steady state—reflecting fluid ILC states, including a naive or quiescent-like state and an ILC2 effector state. Upon disease induction, the continuum shifted rapidly to span a mixed, ILC3-like subset also expressing cytokines characteristic of ILC2s, which we inferred as arising through multiple trajectories. We confirmed the transition potential of quiescent-like and ILC2 states using in vitro experiments, single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) and in vivo fate mapping. Our results highlight the range and flexibility of skin ILC responses, suggesting that immune activities primed in healthy tissues dynamically adapt to provocations and, left unchecked, drive pathological remodelling.
Overall design scRNA-seq profiles of mouse skin ILCs collected every 24h along a time course from healthy (day0) to psoriasis (day4). scATAC-seq profiles of ILC from healthy skin (day0) to psoriasis (day4).
Contributor(s) Bielecki P, Riesenfeld SJ, Hütter JK, Torlai Triglia E, Kowalczyk MS, Ricardo-Gonzalez RR, Amezcua Vesely MC, Kroehling L, Slyper M, Muus C, Ludwig LS, Christian E, Tao L, Kedaigle AJ, Steach HR, York AG, Skadow MH, Yaghoubi P, Dionne D, Jarret A, McGee HM, Porter CB, Licona-Limón P, Bailis W, Jackson RP, Gagliani N, Lian M, Xu H, Gasteiger G, Locksley RM, Regev A, Flavell RA
Citation(s) 33536623, 37398022
Submission date Apr 29, 2020
Last update date Sep 11, 2023
Contact name Elena Torlai Triglia
Organization name Broad Institute
Lab Aviv Regev
Street address 415 Main Street
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
Platforms (2)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL21626 NextSeq 550 (Mus musculus)
Samples (7)
GSM4506037 Time_course_day0
GSM4506038 Time_course_day1
GSM4506039 Time_course_day2
BioProject PRJNA629379
SRA SRP259201

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE149622_RAW.tar 1.9 Gb (http)(custom) TAR (of BED, MTX, TBI, TSV)
GSE149622_RNA_timecourse_sctransform_barcodes.tsv.gz 122.7 Kb (ftp)(http) TSV
GSE149622_RNA_timecourse_sctransform_count_data_matrix.mtx.gz 140.7 Mb (ftp)(http) MTX
GSE149622_RNA_timecourse_sctransform_genes.tsv.gz 57.0 Kb (ftp)(http) TSV
GSE149622_RNA_timecourse_sctransform_norm_data_matrix.mtx.gz 149.2 Mb (ftp)(http) MTX
GSE149622_RNA_timecourse_sctransform_scale_data_matrix.mtx.gz 2.0 Gb (ftp)(http) MTX
GSE149622_RNA_timecourse_sctransform_variable_genes.tsv.gz 11.4 Kb (ftp)(http) TSV
GSE149622_RNA_timecourse_unadjusted_barcodes.tsv.gz 122.7 Kb (ftp)(http) TSV
GSE149622_RNA_timecourse_unadjusted_genes.tsv.gz 66.5 Kb (ftp)(http) TSV
GSE149622_RNA_timecourse_unadjusted_matrix.mtx.gz 144.1 Mb (ftp)(http) MTX
GSE149622_fluorescent_proteins.fa.gz 2.0 Kb (ftp)(http) FA
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap