Suppressing Sema3A expression in muscle satellite cells affects terminal Schwann cells after muscle and nerve injury
Bibliographic record
Abstract
To examine the role of Sema3A expression in satellite cells (SCs) and terminal Schwann cells (TSCs) in neuromuscular junction (NMJs) formation, expression was investigated during recovery from muscle‐ or nerve‐crush injuries in muscle from mice with a SC‐specific knockout of Sema3A. We tested the hypothesis that loss of SC‐specific Sema3A expression would disrupt TSC gene and protein expression after both injuries. Gene expression in synaptic areas was studied using RNAscope multiplex fluorescence in situ hybridisation (ISH, Advanced Cell Diagnostics) to examine TSCs (Sema3A, S100B, P75NGFR), Pax7+ SCs, and Westerns to assay proteins (Sema3A and S100B, and γAchR, related to denervation). Muscle from transgenics with tamoxifen‐induced conditional knockout, and two control groups (injured non‐knockouts and no‐surgery SC‐specific knockouts) were examined 14 and 21days after nerve crush and 21 and 35days after muscle crush (ethics approval A30‐142‐0 (Kyushu U) and F14‐15 UManitoba). Expression sites (number, area, and intensity) for Sema3A, S100B, P75NGFR and Pax7 mRNA were imaged, measured (Celleste software) and analyzed (ANOVA, linear regression, and Principal Component Analysis, PCA) as a function of regeneration time. After muscle crush, P75NGFR expression was higher in SC‐specific Sema3A knockout mice (days 21 and 35) than in non‐knockout controls (p<0.001 Tukey's, df=16) suggesting an increased number of TSCs. γAchR protein was highest at day 21 vs. controls (p<0.001 Tukey's df=32) and correlated to Pax7 intensity in SCs. S100B expression correlated with regeneration time (p<0.01, df=34). S100B protein decreased at day 21 (Tukey's, p<0.001), possibly due to loss of TSCs by out‐migration or cell death, or lack of S100B promotor activity. After nerve crush, P75NGFR expression was higher at day 21 in knockouts than in controls and correlated to Sema3A expression intensity. γAchR protein correlated with P75NGFR and Pax7 expression, indicating SCs increase after denervation or that Pax7 expression/SC increases. S100B and Sema3A proteins in non‐knockout controls were lower at day 14 after nerve injury (2‐way Anova, p<0.001) and increased at day 21 (p<0.001), changes not seen in SC‐specific Sema3A knockout mice. Combining all data for both injuries in PCAs, TSC sites (colocalized P75NGFR, Sema3A and S100B expression) increased with increased S100B and Sema3A proteins (Factors 1 and 2 accounted for 51.8% of variance). PCA of SC sites (overlap of Pax7, S100B, and Sema3A expression) showed Sema3A mRNA and protein and S100B accounted for 30.9% of variance in SCs. Loss of SC‐specific Sema3A expression accelerated denervation after muscle injury. PCAs showed TSC function depends on Sema3A and S100B in reinnervation. Results advance our understanding of synaptic interactions of TSCs and SCs in vivo . This complex interaction between TSCs and SCs during reinnervation and regeneration opens an important new aspect of nerve‐muscle interaction at the cellular level, with possible implications for diseases where those interactions decline, such as amyotrophic lateral sclerosis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".