Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma
Abstract Background Cerebellar neurogenesis involves the generation of large numbers of cerebellar granule neurons (GNs) throughout development of the cerebellum, a process that involves tight regulation of proliferation and differentiation of granule neuron progenitors (GNPs). A number of transcrip...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-07-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-021-01071-8 |
| _version_ | 1818656305651384320 |
|---|---|
| author | Wenqin Luo Guan Ning Lin Weichen Song Yu Zhang Huadong Lai Man Zhang Juju Miao Xiaomu Cheng Yongjie Wang Wang Li Wenxiang Wei Wei-Qiang Gao Ru Yang Jia Wang |
| author_facet | Wenqin Luo Guan Ning Lin Weichen Song Yu Zhang Huadong Lai Man Zhang Juju Miao Xiaomu Cheng Yongjie Wang Wang Li Wenxiang Wei Wei-Qiang Gao Ru Yang Jia Wang |
| author_sort | Wenqin Luo |
| collection | DOAJ |
| description | Abstract Background Cerebellar neurogenesis involves the generation of large numbers of cerebellar granule neurons (GNs) throughout development of the cerebellum, a process that involves tight regulation of proliferation and differentiation of granule neuron progenitors (GNPs). A number of transcriptional regulators, including Math1, and the signaling molecules Wnt and Shh have been shown to have important roles in GNP proliferation and differentiation, and deregulation of granule cell development has been reported to be associated with the pathogenesis of medulloblastoma. While the progenitor/differentiation states of cerebellar granule cells have been broadly investigated, a more detailed association between developmental differentiation programs and spatial gene expression patterns, and how these lead to differential generation of distinct types of medulloblastoma remains poorly understood. Here, we provide a comparative single-cell spatial transcriptomics analysis to better understand the similarities and differences between developing granule and medulloblastoma cells. Results To acquire an enhanced understanding of the precise cellular states of developing cerebellar granule cells, we performed single-cell RNA sequencing of 24,919 murine cerebellar cells from granule neuron-specific reporter mice (Math1-GFP; Dcx-DsRed mice). Our single-cell analysis revealed that there are four major states of developing cerebellar granule cells, including two subsets of granule progenitors and two subsets of differentiating/differentiated granule neurons. Further spatial transcriptomics technology enabled visualization of their spatial locations in cerebellum. In addition, we performed single-cell RNA sequencing of 18,372 cells from Patched +/− mutant mice and found that the transformed granule cells in medulloblastoma closely resembled developing granule neurons of varying differentiation states. However, transformed granule neuron progenitors in medulloblastoma exhibit noticeably less tendency to differentiate compared with cells in normal development. Conclusion In sum, our study revealed the cellular and spatial organization of the detailed states of cerebellar granule cells and provided direct evidence for the similarities and discrepancies between normal cerebellar development and tumorigenesis. |
| first_indexed | 2024-12-17T03:23:29Z |
| format | Article |
| id | doaj.art-e67fb43ca2fd488e9f46fa4b5afde732 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-17T03:23:29Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-e67fb43ca2fd488e9f46fa4b5afde7322022-12-21T22:05:28ZengBMCBMC Biology1741-70072021-07-0119112310.1186/s12915-021-01071-8Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastomaWenqin Luo0Guan Ning Lin1Weichen Song2Yu Zhang3Huadong Lai4Man Zhang5Juju Miao6Xiaomu Cheng7Yongjie Wang8Wang Li9Wenxiang Wei10Wei-Qiang Gao11Ru Yang12Jia Wang13State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering, Shanghai Jiao Tong UniversityShanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering & Med-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, 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, Shanghai Jiao Tong UniversityDepartment of Cell Biology, School of Medicine, Soochow UniversityState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, 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, 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, Shanghai Jiao Tong UniversityAbstract Background Cerebellar neurogenesis involves the generation of large numbers of cerebellar granule neurons (GNs) throughout development of the cerebellum, a process that involves tight regulation of proliferation and differentiation of granule neuron progenitors (GNPs). A number of transcriptional regulators, including Math1, and the signaling molecules Wnt and Shh have been shown to have important roles in GNP proliferation and differentiation, and deregulation of granule cell development has been reported to be associated with the pathogenesis of medulloblastoma. While the progenitor/differentiation states of cerebellar granule cells have been broadly investigated, a more detailed association between developmental differentiation programs and spatial gene expression patterns, and how these lead to differential generation of distinct types of medulloblastoma remains poorly understood. Here, we provide a comparative single-cell spatial transcriptomics analysis to better understand the similarities and differences between developing granule and medulloblastoma cells. Results To acquire an enhanced understanding of the precise cellular states of developing cerebellar granule cells, we performed single-cell RNA sequencing of 24,919 murine cerebellar cells from granule neuron-specific reporter mice (Math1-GFP; Dcx-DsRed mice). Our single-cell analysis revealed that there are four major states of developing cerebellar granule cells, including two subsets of granule progenitors and two subsets of differentiating/differentiated granule neurons. Further spatial transcriptomics technology enabled visualization of their spatial locations in cerebellum. In addition, we performed single-cell RNA sequencing of 18,372 cells from Patched +/− mutant mice and found that the transformed granule cells in medulloblastoma closely resembled developing granule neurons of varying differentiation states. However, transformed granule neuron progenitors in medulloblastoma exhibit noticeably less tendency to differentiate compared with cells in normal development. Conclusion In sum, our study revealed the cellular and spatial organization of the detailed states of cerebellar granule cells and provided direct evidence for the similarities and discrepancies between normal cerebellar development and tumorigenesis.https://doi.org/10.1186/s12915-021-01071-8CerebellumDevelopment of granule cellsGranule neuron progenitorsDifferentiated granule neuronsSHH medulloblastomaSingle-cell RNA sequencing |
| spellingShingle | Wenqin Luo Guan Ning Lin Weichen Song Yu Zhang Huadong Lai Man Zhang Juju Miao Xiaomu Cheng Yongjie Wang Wang Li Wenxiang Wei Wei-Qiang Gao Ru Yang Jia Wang Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma BMC Biology Cerebellum Development of granule cells Granule neuron progenitors Differentiated granule neurons SHH medulloblastoma Single-cell RNA sequencing |
| title | Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma |
| title_full | Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma |
| title_fullStr | Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma |
| title_full_unstemmed | Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma |
| title_short | Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma |
| title_sort | single cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma |
| topic | Cerebellum Development of granule cells Granule neuron progenitors Differentiated granule neurons SHH medulloblastoma Single-cell RNA sequencing |
| url | https://doi.org/10.1186/s12915-021-01071-8 |
| work_keys_str_mv | AT wenqinluo singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT guanninglin singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT weichensong singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT yuzhang singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT huadonglai singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT manzhang singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT jujumiao singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT xiaomucheng singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT yongjiewang singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT wangli singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT wenxiangwei singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT weiqianggao singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT ruyang singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma AT jiawang singlecellspatialtranscriptomicanalysisrevealscommonanddivergentfeaturesofdevelopingpostnatalgranulecerebellarcellsandmedulloblastoma |