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Series GSE189896 Query DataSets for GSE189896
Status Public on Nov 11, 2022
Title Extra-hematopoietic immunomodulatory role of the guanine exchange factor DOCK-2 [MethylCap-Seq]
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary The molecular basis of stromal immunomodulation is still unresolved. Here, we show a novel function for dedicator of cytokinesis 2 (DOCK2) in regulating extra-hematopoietic immune function of three independent stromal cell sources: induced pluripotent stem cells (iPSC)-derived mesodermal stromal cell (iPS-MSC), severe combined immunodeficiency (SCID) patient-derived fibroblasts and CRISPR/Cas9 knockout cells (iPS-MSCDOCK2KO). We first reprogrammed human mesenchymal stromal cells (MSC) into iPSC before differentiating the iPSCs back into MSC. Immature iPS-MSCs lacked immunosuppressive potential. Successive phenotypic maturation facilitated immunomodulatory function, while maintaining clonogenicity, comparable to parental MSCs. Sequential RNA-seq displayed time-dependent immune-related gene expression eventually resembling parental MSCs. SCID patient-derived fibroblasts harboring bi-allelic DOCK2 mutations also showed significantly reduced immunomodulatory capacity compared to non-mutated fibroblasts. CRISPR/Cas9-mediated DOCK2 knockout in healthy iPSCs resulted in significantly reduced immunomodulatory capacity, reduced F-actin stress-fibers, and a disturbed subcellular localization of CDC42 activation. We provide first evidence for extra-hematopoietic immunomodulation by the guanin exchange factor DOCK2. This suggests that persisting immune disease after successful blood stem cell transplantation in SCID patients could in part be due to loss-of-function DOCK2 mutations.
 
Overall design MethylCap-seq analysis of the maturation of induced pluripotent stem cells (iPSCs) derived from Mesenchymal stromal cells (bone marrow and unbilical cord derived MSCs) into MSCs compared to their parental MSCs
 
Contributor(s) Poupardin R, Strunk D
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Submission date Nov 30, 2021
Last update date Nov 11, 2022
Contact name Rodolphe Poupardin
E-mail(s) rodolphe.poupardin@pmu.ac.at
Organization name Paracelsus Medizinische Privatuniversität
Lab Institute for Cell Therapy
Street address Strubergasse 22
City Salzburg
ZIP/Postal code 5020
Country Austria
 
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (50)
GSM5709144 iPS-P0-BM-Alice2_270
GSM5709145 iPS-P0-BM-Alice3_271
GSM5709146 iPS-P0-BM-Betty1_272
This SubSeries is part of SuperSeries:
GSE189898 Extra-hematopoietic immunomodulatory role of the guanine exchange factor DOCK-2
Relations
BioProject PRJNA784968

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Supplementary file Size Download File type/resource
GSE189896_Counts_QSEA_Methylcap_iPSC_maturation.csv.gz 224.7 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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