Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Human Primary Specimens
2.2. Genomic DNA Extraction and Single Nucleotide Polymorphism (SNP) Genotyping
2.3. Specimen Dissociation and Cell Isolation
2.4. Single-Cell RNA Sequencing (scRNA-seq) and Data Pre-Processing
2.5. Cell-Clustering and Cluster Annotation
2.6. Organoid Development and Culture
2.7. Organoid Imaging and Quantitative Analysis
2.8. RNA Extraction and RT-qPCR
2.9. cAMP Assay
2.10. Histology
2.11. Immunofluorescence
2.12. Statistical Analysis
3. Results
3.1. Integrating Patient’s Biology into Organoid Model System
3.2. Single-Cell Analysis Unveils Pro-Fibrotic Transcriptional Signatures and Fibroblastic Cellular Heterogeneity in FD Lesions
3.3. Organoid Generation and Morphological Assessment
3.4. PDOs Exhibit Enrichment of FD-Relevant Gene Signatures and Cellular Microenvironment
3.5. PDOs Recapitulate the Genetic Abnormality, Metabolic Alteration, and Functional Defects of Corresponding FD Tissues
3.6. PDOs Display Non-Aligned, Isotropic Distribution Patterns of Extracellular and Cellular Components
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Donor | Gender | Age | Site | Mutation |
---|---|---|---|---|
FD1 | M | 18 | Nasal cavity/maxillary sinus | R201H |
FD2 | M | 19 | Zygomaticomaxillary | R201C |
FD3 | F | 25 | Hemiface/mandible | R201H |
FD4 | M | 12 | Mandible | R201H |
FD5 | M | 14 | Forehead/upper orbit | R201H |
HV1 | F | 28 | Zygomatic/mandible | None |
HV2 | F | 23 | Hemiface/mandible | None |
HV3 | M | 22 | Zygomatic/mandible | None |
HV4 | M | 19 | Zygomatic/mandible | None |
HV5 | F | 25 | Zygomatic/hemiface | None |
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Kim, H.-Y.; Charton, C.; Shim, J.H.; Lim, S.Y.; Kim, J.; Lee, S.; Ohn, J.H.; Kim, B.K.; Heo, C.Y. Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia. Cells 2024, 13, 729. https://doi.org/10.3390/cells13090729
Kim H-Y, Charton C, Shim JH, Lim SY, Kim J, Lee S, Ohn JH, Kim BK, Heo CY. Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia. Cells. 2024; 13(9):729. https://doi.org/10.3390/cells13090729
Chicago/Turabian StyleKim, Ha-Young, Clémentine Charton, Jung Hee Shim, So Young Lim, Jinho Kim, Sejoon Lee, Jung Hun Ohn, Baek Kyu Kim, and Chan Yeong Heo. 2024. "Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia" Cells 13, no. 9: 729. https://doi.org/10.3390/cells13090729