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Status |
Public on Apr 05, 2024 |
Title |
Shared and compartment-specific processes in nucleus pulposus and annulus fibrosus during intervertebral disc degeneration |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Elucidating how cell populations promote onset and progression of intervertebral disc degeneration (IDD) has the potential to enable more precise therapeutic targeting of cells and mechanisms. Single cell RNA-sequencing (scRNA-seq) was performed on surgically separated annulus fibrosus (AF) (19,978; 26,983 cells) and nucleus pulposus (NP) (20,884; 24,489 cells) from healthy and diseased human intervertebral discs (IVD). In both tissue types, we observed depletion of cell subsets involved in maintenance of healthy IVD, specifically the immature cell subsets – fibroblast progenitors and stem cells – indicative of an impairment of normal tissue self-renewal. We also identified tissue-specific changes. In NP, several fibrotic populations were increased in degenerated IVD, indicating tissue-remodeling. In degenerated AF, we identified a novel disease-associated subset, which is a stem cell-derived abnormally differentiated chondrocytic population and expresses disease-promoting genes. It was associated with pathogenic biological processes and the main gene regulatory networks includedthrombospondinsignaling and FOXO1 transcription factor. Our data reveal new insights of both shared and tissue-specific changes in specific cell populations in AF and NP during IVD degeneration. These identified mechanisms and molecules are novel and more precise targets for IDD prevention and treatment.
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Overall design |
Single cell level analysis of annulus fibrosus and nucleus pulposus tissues from human diseased (n=10, n=8) intervertebral discs.
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Contributor(s) |
Swahn H, Mertens J, Olmer M, Myers K, Mondala TS, Natarajan P, Head SR, Alvarez-Garcia O, Lotz MK |
Citation(s) |
38403470 |
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Submission date |
Apr 27, 2023 |
Last update date |
Apr 06, 2024 |
Contact name |
Padma Natarajan |
E-mail(s) |
ccbb@scripps.edu
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Organization name |
The Scripps Research Institute
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Department |
CCBB
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Street address |
10550 N.Torrey Pines Road
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City |
La Jolla |
State/province |
CA |
ZIP/Postal code |
92037 |
Country |
USA |
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Platforms (1) |
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Samples (18)
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GSM7235331 |
diseased annulus fibrosus (Thompson grade III-IV) single cell RNAseq, donor5 |
GSM7235332 |
diseased annulus fibrosus (Thompson grade III-IV) single cell RNAseq, donor6 |
GSM7235333 |
diseased annulus fibrosus (Thompson grade II-III) single cell RNAseq, donor1 |
GSM7235334 |
diseased annulus fibrosus (Thompson grade III) single cell RNAseq, donor1 |
GSM7235335 |
diseased annulus fibrosus (Thompson grade III) single cell RNAseq, donor2 |
GSM7235336 |
diseased annulus fibrosus (Thompson grade II-III) single cell RNAseq, donor2 |
GSM7235337 |
diseased annulus fibrosus (Thompson grade III-IV) single cell RNAseq, donor1 |
GSM7235338 |
diseased annulus fibrosus (Thompson grade III-IV) single cell RNAseq, donor2 |
GSM7235339 |
diseased annulus fibrosus (Thompson grade III-IV) single cell RNAseq, donor3 |
GSM7235340 |
diseased annulus fibrosus (Thompson grade III-IV) single cell RNAseq, donor4 |
GSM7235341 |
diseased nucleus pulposus (Thompson grade II-III) single cell RNAseq, donor1 |
GSM7235342 |
diseased nucleus pulposus (Thompson grade III) single cell RNAseq, donor1 |
GSM7235343 |
diseased nucleus pulposus (Thompson grade III) single cell RNAseq, donor2 |
GSM7235344 |
diseased nucleus pulposus (Thompson grade II-III) single cell RNAseq, donor2 |
GSM7235345 |
diseased nucleus pulposus (Thompson grade III-IV) single cell RNAseq, donor1 |
GSM7235346 |
diseased nucleus pulposus (Thompson grade III-IV) single cell RNAseq, donor2 |
GSM7235347 |
diseased nucleus pulposus (Thompson grade III-IV) single cell RNAseq, donor3 |
GSM7235348 |
diseased nucleus pulposus (Thompson grade III-IV) single cell RNAseq, donor4 |
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This SubSeries is part of SuperSeries: |
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Relations |
BioProject |
PRJNA962589 |
Supplementary file |
Size |
Download |
File type/resource |
GSE230808_RAW.tar |
703.2 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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