NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE190542 Query DataSets for GSE190542
Status Public on Sep 26, 2022
Title Germline ERCC6L2 mutations lead to impaired erythropoiesis and reshaping of the bone marrow niche
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Despite the inclusion of inherited myeloid malignancies as a separate entity in the WHO Classification, our understanding of the etiology of familial leukemia remains limited. ERCC6L2-deficiency is a rare, life-threatening inherited condition that gives rise to bone marrow failure (BMF), myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) resulting from germline mutations in DNA repair factor ERCC6L2. Here we employ a lentiviral shRNA approach to functionally characterize the impact of ERCC6L2 loss on hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). By combining cell culture assays and transcriptomic analysis of knockdown and ERCC6L2-mutated patient cells, we find that ERCC6L2-deficiency reduces HSPC clonogenic potential and delays erythropoiesis, while in MSCs it induces a significant lineage skewing, with increased osteogenesis and suppressed adipogenesis. Altogether, we demonstrate that ERCC6L2-deficiency impacts both hematopoietic and stromal compartments, and that our ex vivo model recapitulates patient phenotypes, providing a robust system to study germline mutations in hematological malignancies.
 
Overall design 30 Samples. 6 patient bone marrow and 24 Primary cells. 2 knockdown and corresponding scramble samples per media condition, except for Erythroid media where there are 4 samples each across two batches.
 
Contributor(s) Armes H, Bewicke-Copley F, Rio-Machin A, Wozniak A, Di Bella D, Philippe C, Tummala H, Wang J, Ezponda T, Prosper F, Dokal I, Vulliamy T, Kilpivaara O, Wartiovaara-Kautto U, Fitzgibbon J, Rouault-Pierre K
Citation(s) 36156210
Submission date Dec 09, 2021
Last update date Jan 03, 2023
Contact name Findlay Bewicke-Copley
E-mail(s) f.copley@qmul.ac.uk
Organization name Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London
Street address John Vane Science Centre, Barts Cancer Institute
City London
ZIP/Postal code EC1M 6BQ
Country United Kingdom
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (30)
GSM5725485 Erythroid media Patient 1
GSM5725486 Erythroid media Patient 2
GSM5725487 Erythroid media Scramble replicate 1
Relations
BioProject PRJNA787532
SRA SRP349996

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
GSE190542_RAW.tar 5.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
External link. Please review our privacy policy.