Single-cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide-induced bladder injury
Abstract Cyclophosphamide is a commonly used chemotherapeutic drug to treat cancer with side effects that trigger bladder injury and hemorrhagic cystitis. Although previous studies have demonstrated that certain cell subsets and communications are activated to drive the repair and regeneration of bl...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-05-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-03740-6 |
| _version_ | 1818938216925888512 |
|---|---|
| author | Xiaomu Cheng Huadong Lai Wenqin Luo Man Zhang Juju Miao Weichen Song Shunpeng Xing Jia Wang Wei-Qiang Gao |
| author_facet | Xiaomu Cheng Huadong Lai Wenqin Luo Man Zhang Juju Miao Weichen Song Shunpeng Xing Jia Wang Wei-Qiang Gao |
| author_sort | Xiaomu Cheng |
| collection | DOAJ |
| description | Abstract Cyclophosphamide is a commonly used chemotherapeutic drug to treat cancer with side effects that trigger bladder injury and hemorrhagic cystitis. Although previous studies have demonstrated that certain cell subsets and communications are activated to drive the repair and regeneration of bladder, it is not well understood how distinct bladder cell subsets function synergistically in this process. Here, we used droplet-based single-cell RNA sequencing (scRNA-seq) to profile the cell types within the murine bladder mucous layer under normal and injured conditions. Our analysis showed that superficial cells are directly repaired by cycling intermediate cells. We further identified two resident mesenchymal lineages (Acta2 + myofibroblasts and Cd34 + fibroblasts). The delineation of cell-cell communications revealed that Acta2 + myofibroblasts upregulated Fgf7 expression during acute injury, which activated Fgfr signaling in progenitor cells within the basal/intermediate layers to promote urothelial cell growth and repair. Overall, our study contributes to a more comprehensive understanding of the cellular dynamics during cyclophosphamide-induced bladder injury and may help identify important niche factors contributing to the regeneration of injured bladders. |
| first_indexed | 2024-12-20T06:04:20Z |
| format | Article |
| id | doaj.art-479b6c2a47264445a59b1f0bb44b773f |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-20T06:04:20Z |
| publishDate | 2021-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-479b6c2a47264445a59b1f0bb44b773f2022-12-21T19:50:51ZengNature Publishing GroupCell Death and Disease2041-48892021-05-0112511510.1038/s41419-021-03740-6Single-cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide-induced bladder injuryXiaomu Cheng0Huadong Lai1Wenqin Luo2Man Zhang3Juju Miao4Weichen Song5Shunpeng Xing6Jia Wang7Wei-Qiang Gao8State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong UniversityMed-X Research Institute, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong UniversityMed-X Research Institute, Shanghai Jiao Tong UniversityMed-X Research Institute, Shanghai Jiao Tong UniversityShanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineDepartment of Critical Care Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong UniversityAbstract Cyclophosphamide is a commonly used chemotherapeutic drug to treat cancer with side effects that trigger bladder injury and hemorrhagic cystitis. Although previous studies have demonstrated that certain cell subsets and communications are activated to drive the repair and regeneration of bladder, it is not well understood how distinct bladder cell subsets function synergistically in this process. Here, we used droplet-based single-cell RNA sequencing (scRNA-seq) to profile the cell types within the murine bladder mucous layer under normal and injured conditions. Our analysis showed that superficial cells are directly repaired by cycling intermediate cells. We further identified two resident mesenchymal lineages (Acta2 + myofibroblasts and Cd34 + fibroblasts). The delineation of cell-cell communications revealed that Acta2 + myofibroblasts upregulated Fgf7 expression during acute injury, which activated Fgfr signaling in progenitor cells within the basal/intermediate layers to promote urothelial cell growth and repair. Overall, our study contributes to a more comprehensive understanding of the cellular dynamics during cyclophosphamide-induced bladder injury and may help identify important niche factors contributing to the regeneration of injured bladders.https://doi.org/10.1038/s41419-021-03740-6 |
| spellingShingle | Xiaomu Cheng Huadong Lai Wenqin Luo Man Zhang Juju Miao Weichen Song Shunpeng Xing Jia Wang Wei-Qiang Gao Single-cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide-induced bladder injury Cell Death and Disease |
| title | Single-cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide-induced bladder injury |
| title_full | Single-cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide-induced bladder injury |
| title_fullStr | Single-cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide-induced bladder injury |
| title_full_unstemmed | Single-cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide-induced bladder injury |
| title_short | Single-cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide-induced bladder injury |
| title_sort | single cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide induced bladder injury |
| url | https://doi.org/10.1038/s41419-021-03740-6 |
| work_keys_str_mv | AT xiaomucheng singlecellanalysisrevealsurothelialcellheterogeneityandregenerativecuesfollowingcyclophosphamideinducedbladderinjury AT huadonglai singlecellanalysisrevealsurothelialcellheterogeneityandregenerativecuesfollowingcyclophosphamideinducedbladderinjury AT wenqinluo singlecellanalysisrevealsurothelialcellheterogeneityandregenerativecuesfollowingcyclophosphamideinducedbladderinjury AT manzhang singlecellanalysisrevealsurothelialcellheterogeneityandregenerativecuesfollowingcyclophosphamideinducedbladderinjury AT jujumiao singlecellanalysisrevealsurothelialcellheterogeneityandregenerativecuesfollowingcyclophosphamideinducedbladderinjury AT weichensong singlecellanalysisrevealsurothelialcellheterogeneityandregenerativecuesfollowingcyclophosphamideinducedbladderinjury AT shunpengxing singlecellanalysisrevealsurothelialcellheterogeneityandregenerativecuesfollowingcyclophosphamideinducedbladderinjury AT jiawang singlecellanalysisrevealsurothelialcellheterogeneityandregenerativecuesfollowingcyclophosphamideinducedbladderinjury AT weiqianggao singlecellanalysisrevealsurothelialcellheterogeneityandregenerativecuesfollowingcyclophosphamideinducedbladderinjury |