[Paper Review] CPTCs Drive Somatic-Visceral Communication via the Wnt Axis in Somatic Mechanotherapy: A Single-Cell Deep Learning Study

Haixiang Huang, Zhenwei Zhang+11 more|arXiv (Cornell University)|Feb 5, 2026

Cellular Mechanics and Interactions0 citations

TL;DR

The study uses an interpretable single-cell deep learning framework to show that CD34+PDGFRα+ telocytes (CPTCs) act as mechanosensors during somatic mechanotherapy, activating a Wnt-driven regenerative signaling axis to repair colonic epithelium.

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.

Motivation & Objective

• 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.

Proposed method

• 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.

Experimental results

Research questions

• RQ1 What cells mediate somatic mechanical cues to elicit visceral repair?
• RQ2 Do CPTCs act as mechanosensors in both fascia and colon during colitis?
• RQ3 How does somatic mechanotherapy alter transcriptional programs and intercellular networks to promote regeneration via Wnt signaling?

Key findings

• 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.