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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 16, 2022 |
| Title |
mRAN expression profiles in mesenchymal progenitor cells freshly-sorted from Wild Type and Lama4-deficient mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Bone marrow (BM) niche contributes to hematopoietic regeneration under stress like irradiation and leukemia. However, the mechanisms remain poorly defined. We here report that Lama4 deletion in mice results in reduction of mesenchymal progenitors (MPCs) and endothelial cells in BM. Following irradiation, Lama4-/- mice displayed impaired hematopoiesis recovery accompanied with dysregulation of BM niche factors like angiopoietin-1 and Tgfb1 in the MPCs. Post-transplantation of MLL-AF9 acute myeloid leukemia (AML) cells, we observed accelerated AML onset in Lama4-/- mice. Moreover, these Lama4-/- AML mice displayed faster relapse after therapeutic BM transplantation. Mechanistically, Lama4-/- niche promoted AML cell proliferation and chemoresistance to chemotherapy cytarabine by conferring AML greater antioxidant activity. Together, our study demonstrates that Lama4 is required to maintain hematopoietic niche integrity and to suppress AML progression and chemoresistance by restricting metabolic defense support to AML. Therefore, activating Lama4 signaling pathways may offer potential new therapeutic options for AML.
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| Overall design |
Examination of mRNA profiles in mesenchymal progenitor cells (CD45-TER119-CD31-CD44-CD51+SCA1-) freshly-sorted from 3 wild type (WT) and 3 Lama4-/- mice 6 weeks post sublethetal irridation (7Gy)
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| Contributor(s) |
Qian H, Kondo M, Cai H, Sandhow L, Xiao P, Johansson A, Sasaki T, Tryggvarson K, Ekblom M |
| Citation(s) |
34958665 |
| Submission date |
Feb 24, 2021 |
| Last update date |
Feb 16, 2022 |
| Contact name |
Hong Qian |
| E-mail(s) |
hong.qian@ki.se
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| Organization name |
Karolinska Institute
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| Department |
Department of Medicine
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| Lab |
Hong Qian Group
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| Street address |
Hälsovägen 7C (lastkaj), 14157 Huddinge/Stockholm
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| City |
Stockholm |
| ZIP/Postal code |
171 77 |
| Country |
Sweden |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA704574 |
| SRA |
SRP307919 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE167404_Gene_counts_matrix.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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