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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 08, 2024 |
| Title |
ONTOGENY SHAPES THE ABILITY OF ETV6-RUNX1 TO ENHANCE HEMATOPOIETIC STEM CELL SELF-RENEWAL AND DISRUPT EARLY LYMPHOPOIESIS [in vivo] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The ETV6-RUNX1 (E/R) translocation, found in approximately 30% of pediatric B-cell acute lymphoblastic leukemia (ALL) cases, originates prenatally. Although hematopoietic stem cells (HSCs) have been proposed as the cell of origin for E/R-ALL, definitive evidence for this has been lacking. Here, we develop an E/R-inducible transgenic mouse model and observe that E/R rapidly expands the pool of phenotypic HSCs and block early B cell development. By leveraging the reversibility of the model, we demonstrate functional rather than merely phenotypic HSC expansion. At a molecular level, E/R activates immune checkpoint pathways, which is more pronounced in fetal cells. Comparison of fetal and adult HSCs reveals that although E/R disrupts HSC differentiation in both, fetal cells have a competitive advantage, especially in a setting of viral mimicry. These findings provide new insights into the nature of preleukemic clones associated with E/R and suggest potential benefits of immune checkpoint inhibition for their eradication.
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| Overall design |
RNA-seq was performed on HSCs (Lin- Kit+ Sca1+ CD48- CD150+) sorted from control (uninduced) or E/R-induced mice, n = 3 replicates/group
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| Contributor(s) |
Eldeeb M, Konturek-Ciesla A, Zhang Q, Kharazi S, Tingvall-Gustafsson J, Ungerbäck J, Sigvardsson M, Bryder D |
| Citation(s) |
38243088 |
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| Submission date |
Jul 26, 2023 |
| Last update date |
Apr 08, 2024 |
| Contact name |
Mohamed Eldeeb |
| E-mail(s) |
mohamed.eldeeb@med.lu.se
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| Organization name |
Lund University
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| Street address |
DMH, BMC B12
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| City |
Lund |
| ZIP/Postal code |
221 84 |
| Country |
Sweden |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE239344 |
ONTOGENY SHAPES THE ABILITY OF ETV6-RUNX1 TO ENHANCE HEMATOPOIETIC STEM CELL SELF-RENEWAL AND DISRUPT EARLY LYMPHOPOIESIS |
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| Relations |
| BioProject |
PRJNA998849 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE239340_STRINGTIE_2020_86_R1_GeneData_TPM.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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