[论文解读] CPTCs Drive Somatic-Visceral Communication via the Wnt Axis in Somatic Mechanotherapy: A Single-Cell Deep Learning Study
该研究使用可解释的单细胞深度学习框架表明 CD34+PDGFRα+ 纤毛细胞(CPTCs)在体细胞力治疗中充当机械感应器,激活一个由 Wnt 驱动的再生信号轴以修复结肠上皮。
Somatic mechanical stimulation (e.g., acupuncture) exerts systemic immunomodulatory effects, yet the cellular bridge translating peripheral physical force into visceral repair remains elusive. Here, employing a custom interpretable deep learning framework (CARSS) on single-cell RNA sequencing data, we identify CD34$^{+}$PDGFR$α$$^{+}$ telocytes (CPTCs) as the primary mechanosensors in both fascia and colon during bacterial colitis. We show that somatic mechanotherapy triggers an AP-1/Hsp70-dependent transcriptional program in fascial CPTCs, inducing systemic Wnt elevation, which elicits a "transcriptional resonance" in colonic CPTCs, reprogramming their communication network from an inflammatory amplifier to a Wnt-driven regenerative hub. Mechanistically, this axis activates epithelial $β$-catenin/Myc signaling, suppressing apoptosis and restoring barrier integrity independent of immune cells. Our findings define a CPTC-Driven Mechano-Resonance Axis, where CPTCs serve as synchronized relay stations that convert local mechanical cues into systemic regenerative microenvironments.
研究动机与目标
- Identify cellular bridges translating local mechanical cues into systemic visceral responses during somatic mechanotherapy.
- Discover CPTCs as primary mechanosensors in fascia and colon during bacterial colitis.
- Characterize transcriptional programs and signaling axes linking somatic stimulation to colonic regeneration.
提出的方法
- Develop a custom interpretable deep learning framework (CARSS) to analyze single-cell RNA sequencing data.
- Identify CPTCs as the main mechanosensors in fascia and colon under colitis.
- Characterize AP-1/Hsp70-dependent transcriptional programs and consequent systemic Wnt signaling.
- Map intercellular communication networks and their reprogramming from inflammatory to regenerative states.
实验结果
研究问题
- RQ1What cells mediate somatic mechanical cues to elicit visceral repair?
- RQ2Do CPTCs act as mechanosensors in both fascia and colon during colitis?
- RQ3How does somatic mechanotherapy alter transcriptional programs and intercellular networks to promote regeneration via Wnt signaling?
主要发现
- Somatic mechanotherapy engages CPTCs as primary mechanosensors in fascia and colon during colitis.
- An AP-1/Hsp70-dependent transcriptional program in fascial CPTCs triggers systemic Wnt elevation.
- Colonic CPTCs experience a transcriptional resonance, shifting from inflammatory signaling to a Wnt-driven regenerative hub.
- Wnt axis activates epithelial β-catenin/Myc signaling and suppresses epithelial apoptosis, aiding barrier restoration independent of immune cells.
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