General Information
- Project ID
- OEP002972
- Project Name
- Single-cell multiomics reveals the dynamics of pioneer forces driving prostate cancer lineage plasticity
- Description
- The acquisition of cancer cell lineage plasticity, such as the adeno-to-neuroendocrine lineage transition in prostate cancer, has emerged as a mechanism of targeted therapeutic resistance. However, the exact molecular mechanisms underlying this lineage transition remain elusive. Furthermore, developing pharmacological strategies to overcome current therapeutic resistance using clinical-grade inhibitors is imperative. Here, single-cell multiomics analyses (single-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing in the same cell) were performed to systematically evaluate the dynamics of cellular heterogeneity, transcriptomics and epigenetics regulation, and microenvironmental factors in 107,201 cells from mouse prostate cancer samples with complete time series of tumor evolution seen in patients. The pioneer transcription factors Foxa2 and Foxa1 were shown to orchestrate prostate cancer luminal-to-neuroendocrine lineage transition. Foxa2 directly promoted Kit expression in neuroendocrine prostate cancer (NEPC) to dominate neuroendocrine-specific cell communication. Pharmacologic inhibition of Kit signaling significantly suppressed mouse and human NEPC organoid growth both in vitro and in vivo. These findings led to the elucidation of the mechanism underlying luminal-to-neuroendocrine lineage plasticity in prostate cancer, the identification of a unique cell communication network of neuroendocrine cells, and the development of a potential pharmacological strategy for enabling therapeutic sensitivity of castration-resistant NEPC.
- Publications
-
FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer
Han M, Li F, Zhang Y, Dai P, He J, Li Y, Zhu Y, Zheng J, Huang H, Bai F, Gao D. FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer. Cancer Cell. 2022 Nov 14;40(11):1306-1323.e8. doi: 10.1016/j.ccell.2022.10.011. Epub 2022 Nov 3. PMID: 36332622.
(PMID: 36332622) (DOI: 10.1016/j.ccell.2022.10.011) - Related Links
- https://pubmed.ncbi.nlm.nih.gov/36332622/
Project information
- Experiments
- 3
- Samples
- 7
Sample ID Sample Name Sample Subject Type Organism Tissue Create Date OES128952 W2 Animalia Mus musculus prostate 2021-12-12 OES128953 M6 Animalia Mus musculus prostate 2021-12-12 OES128954 Wild type Animalia Mus musculus prostate 2021-12-12 OES128955 M1 Animalia Mus musculus prostate 2021-12-12 OES128957 M2.5 Animalia Mus musculus prostate 2021-12-12 OES128958 M3.5 Animalia Mus musculus prostate 2021-12-12 OES128959 M4.5 Animalia Mus musculus prostate 2021-12-12 - Runs
-
22
Run ID Run Name Experiment Sample Data Num Create Date OER236988 ATAC-seq W2 OEX014923 OES128952 2 2021-12-12 OER236989 ATAC-seq M6 OEX014923 OES128953 2 2021-12-12 OER236991 ChIP-seq FOXA1 W2 OEX014924 OES128952 2 2021-12-12 OER236992 ChIP-seq FOXA1 M6 OEX014924 OES128953 2 2021-12-12 OER236993 ChIP-seq FOXA2 W2 OEX014924 OES128952 2 2021-12-12 OER236994 ChIP-seq FOXA2 M6 OEX014924 OES128953 2 2021-12-12 OER236995 ChIP-seq Input W2 OEX014924 OES128952 2 2021-12-12 OER236996 ChIP-seq Input M6 OEX014924 OES128953 2 2021-12-12 OER236990 scRNA-seq WT OEX014925 OES128954 8 2021-12-12 OER236997 scATAC-seq M1 OEX014925 OES128955 32 2021-12-12 OER236998 scATAC-seq M2.5 OEX014925 OES128957 64 2021-12-12 OER236999 scATAC-seq W2 OEX014925 OES128952 32 2021-12-12 OER237000 scATAC-seq M3.5 OEX014925 OES128958 32 2021-12-12 OER237001 scATAC-seq M4.5 OEX014925 OES128959 32 2021-12-12 OER237002 scATAC-seq M6 OEX014925 OES128953 16 2021-12-12 OER237004 scRNA-seq M1 OEX014925 OES128955 8 2021-12-12 OER237005 scRNA-seq M2.5 OEX014925 OES128957 16 2021-12-12 OER237006 scRNA-seq W2 OEX014925 OES128952 8 2021-12-12 OER237007 scRNA-seq M3.5 OEX014925 OES128958 8 2021-12-12 OER237008 scRNA-seq M4.5 OEX014925 OES128959 12 2021-12-12 OER237009 scRNA-seq M6 OEX014925 OES128953 4 2021-12-12 OER237010 scATAC-seq WT OEX014925 OES128954 32 2021-12-12 - Analysis
-
18
Analysis ID Analysis Title Analysis Type Data Date OEZ008169 ATAC-seq (peaks) Other 2 2021-12-12 OEZ008170 ATAC-seq (bw) Other 2 2021-12-12 OEZ008171 ChIP-seq (peaks) Other 4 2021-12-12 OEZ008172 ChIP-seq (bw) Other 6 2021-12-12 OEZ008173 SC-multiomics cellranger-arc outs (Wild type-1) Other 3 2021-12-12 OEZ008176 SC-multiomics cellranger-arc outs (Wild type-2) Other 3 2021-12-12 OEZ008177 SC-multiomics cellranger-arc outs (W2-1) Other 3 2021-12-12 OEZ008178 SC-multiomics cellranger-arc outs (W2-2) Other 3 2021-12-12 OEZ008179 SC-multiomics cellranger-arc outs (M1-1) Other 3 2021-12-12 OEZ008180 SC-multiomics cellranger-arc outs (M1-2) Other 3 2021-12-12 OEZ008181 SC-multiomics cellranger-arc outs (M2.5-1) Other 3 2021-12-12 OEZ008182 SC-multiomics cellranger-arc outs (M2.5-2) Other 3 2021-12-12 OEZ008183 SC-multiomics cellranger-arc outs (M3.5-1) Other 3 2021-12-12 OEZ008186 SC-multiomics cellranger-arc outs (M4.5-1) Other 3 2021-12-12 OEZ008187 SC-multiomics cellranger-arc outs (M4.5-2) Other 3 2021-12-12 OEZ008188 SC-multiomics cellranger-arc outs (M6) Other 3 2021-12-12 OEZ008190 SC-multiomics cellranger-arc outs (M2.5-3) Other 3 2021-12-12 OEZ008191 SC-multiomics cellranger-arc outs (M2.5-4) Other 3 2021-12-12
Author Information
- Create Date
- 2021-12-09
- Last Modified
- 2023-09-06
- Submission
- Fei Li
- Center for Excellence in Molecular Cell Science/Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences