General Information
- Project ID
- OEP003642
- Project Name
- Identification of a Defensive Niche Cell Population Expressing Gremlin1 in the Spleen to Restrain Chronic Myeloid Leukemia
- Description
- The spleen plays a critical role in the pathogenesis of leukemia. However, our understanding of the splenic niche in regulating leukemic cells is very limited. Herein, we report identification of such a unique splenic niche population. Induced expression of a secreted protein Gremlin1 in a genetically engineered mouse model restrains the disease progression of chronic myeloid leukemia (CML) and synergizes with first-line tyrosine kinase inhibitor (TKI) treatment, whereas blockade of the Gremlin1 protein by a monoclonal antibody enhances the CML development. Intriguingly, the CML-promoting effect of anti-Gremlin1 antibody is most evident in the spleen but not in the bone marrow, which can be abrogated by splenectomy. Genetic ablation of Gremlin1+ cells leads to an accelerated CML progression. Together with analysis of single cell RNA-seq data, we find that Gremlin1 marks a unique stromal cell population in the spleen of not only mice, but also humans. Mechanistically, Gremlin1 induces apoptosis of leukemia stem cells (LSCs) via antagonizing the BMP pathway. Together, we demonstrate that Gremlin1 and Gremlin1+ cells are key defensive niche components in the spleen to limit the progression of CML, revealing an unprecedented mechanism for the body to fight off leukemia.
Project information
- Experiments
- 3
Experiment ID Experiment name Experiment type Create Date OEX027717 Single cell RNA-seq of enzymatically digested CML mouse spleen cells Transcriptomic single cell 2024-04-11 OEX027718 Single cell RNA-seq of enzymatically digested human spleen cell Transcriptomic single cell 2024-04-11 OEX027719 RNA-seq of CML mouse spleen LSK cells Transcriptomic 2024-04-11 - Samples
- 6
Sample ID Sample Name Sample Subject Type Organism Tissue Create Date OES369708 Chip1 of CML mouse spleen cell scRNA-seq Animalia Mus musculus spleen 2024-04-11 OES369709 Chip2 of CML mouse spleen cell scRNA-seq Animalia Mus musculus spleen 2024-04-11 OES369710 Chip1 of human spleen cell scRNA-seq Human Homo sapiens spleen 2024-04-11 OES369711 Chip2 of human spleen cell scRNA-seq Human Homo sapiens spleen 2024-04-11 OES369712 SLSK_IgG Animalia Mus musculus spleen 2024-04-11 OES369713 SLSK_Ab Animalia Mus musculus spleen 2024-04-11 - Runs
-
6
Run ID Run Name Experiment Sample Data Num Create Date OER468997 Chip1 of CML mouse spleen cell scRNA-seq OEX027717 OES369708 3 2024-04-11 OER468998 Chip2 of CML mouse spleen cell scRNA-seq OEX027717 OES369709 3 2024-04-11 OER468999 Chip1 of human spleen cell scRNA-seq OEX027718 OES369710 3 2024-04-11 OER469000 Chip2 of human spleen cell scRNA-seq OEX027718 OES369711 3 2024-04-11 OER469001 SLSK_IgG OEX027719 OES369712 6 2024-04-11 OER469002 SLSK_Ab OEX027719 OES369713 6 2024-04-11
Author Information
- Create Date
- 2022-09-16
- Last Modified
- 2024-04-11
- Submission
- HelenHe Zhu
- State Key Laboratory of Oncogenes and Related Genes, Renji‐Med‐X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China