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| Status |
Public on Apr 30, 2024 |
| Title |
Lin-CD117+CD34+FceRI+ progenitor cells are increased in chronic spontaneous urticaria and predict clinical responsiveness to anti-IgE therapy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Background: Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterised by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineage-CD34hiCD117int/hiFcεRI+ cells in blood have previously been shown to represent a mast cell precursor. Methods: We enumerated FcεRI-, FcεRI+ and FcεRIhi lineage-CD34+CD117+ cells using flow cytometry in blood of patients with CSU (n=55), including 12 patients receiving omalizumab and 43 not receiving omalizumab (n=43). Twenty-two control samples were studied. Disease control and patient response to omalizumab was evaluated using the Urticaria Control Test. We performed single cell RNA sequencing (scRNA-seq) on lineage-CD34hiCD117hi blood cells from a subset of patients with CSU (n=8) and healthy controls (n=4). Results: CSU patients had more Lineage-CD34+CD117+FcεRI+ blood cells than controls. Lineage-CD34+CD117+FcεRI+ cells were significantly higher in patients with CSU who had an objective clinical response to omalizumab when compared to patients who had poor disease control 90 days after initiation of omalizumab. scRNA-seq revealed that lineage-CD34+CD117+FcεRI+ cells contained both lymphoid and myeloid progenitor lineages, with omalizumab responsive patients having proportionally more myeloid progenitors. The myeloid progenitor lineage contained small numbers of true mast cell precursors along with more immature FcεRI- and FcεRI+ myeloid progenitors. Conclusion: Increased blood CD34+CD117+FcεRI+ cells may reflect enhanced bone marrow egress in the setting of CSU. High expression of these cells strongly predicts better clinical responses to the anti-IgE therapy, omalizumab.
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| Overall design |
PBMC were isolated from controls and paitents with CSU prior to treatment with omalizumab. PBMC were labelled with fluorescent antibodies and propidium iodide (PI) and purified using the FACSAria Fusion cell sorter (BD Biosciences). The lineage (Lin) channel included antibodies targeting the markers CD4, CD8, CD14 and CD19, all conjugated to V500. Cells were sorted at low pressure (100 µM nozzle at 20 psi) into PBS. For each sample, two populations of single, live (PI-) cells were sorted; (i) CD34+CD117+Lin- and (ii) Lin+, we recombined these populations at a ratio of 1:1.
Data is from a single BD Rhapsody run, containing 12 samples multiplexed using the human multiplexing kit. Fastq files contain all three library types, WTA (RNA), AbSeq (CITE-Seq) and SMK (sample tag). Fastq files should be processed via the BD Rhapsody pipeline. Supplementary data contains outputs of this pipeline (revision 11), including UMI gene counts table (DBEC_MolsPerCell), sample tag reads and calls (specifying sample information for each barcode). We also include minimal sample information (Sample_info) to identify samples and their original clinical groupings.
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| Contributor(s) |
Finlay CM |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Mar 12, 2024 |
| Last update date |
Apr 30, 2024 |
| Contact name |
Conor M Finlay |
| E-mail(s) |
cofinlay@tcd.ie, conor.finlay@manchester.ac.uk
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| Organization name |
Trinity College Dublin
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| Department |
School of Medicine
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| Street address |
Trinity Translational Medicine Institute, Trinity College Dublin, St. James' Hospital Campus, Trinity College Dublin, Dublin 8
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| City |
Dublin |
| ZIP/Postal code |
D08 W9RT |
| Country |
Ireland |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (1) |
| GSM8143812 |
4 control subjects and 8 patients with chronic spontaneous urticaria |
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| Relations |
| BioProject |
PRJNA1086921 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE261424_Combined_KR1_DBEC_MolsPerCell.csv.gz |
27.1 Mb |
(ftp)(http) |
CSV |
| GSE261424_KR001_abseq.fasta.gz |
1.9 Kb |
(ftp)(http) |
FASTA |
| GSE261424_KR1_Sample_Tag_Calls.csv.gz |
82.0 Kb |
(ftp)(http) |
CSV |
| GSE261424_KR1_Sample_Tag_Metrics.csv.gz |
911 b |
(ftp)(http) |
CSV |
| GSE261424_KR1_Sample_Tag_ReadsPerCell.csv.gz |
162.6 Kb |
(ftp)(http) |
CSV |
| GSE261424_Sample_info.csv.gz |
743 b |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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