CPTCs Drive Somatic-Visceral Communication via the Wnt Axis in Somatic Mechanotherapy: A Single-Cell Deep Learning Study
Haixiang Huang, Zhenwei Zhang, BingBing Shen, Jianming Yue, Lu Mei, Xudong Zhu, Yonghong Shi, Qianmei Zhu, Yeping Shi, Yifan Luo, Yitong Xing, Meng Dai, Qiusheng Chen
Abstract
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.