CPTCs Drive Somatic-Visceral Communication via the Wnt Axis in Somatic Mechanotherapy: A Single-Cell Deep Learning...

Area of Science:

• Cellular biology
• Immunology
• Regenerative medicine

Background:

• Somatic mechanical stimulation, like acupuncture, has known systemic immunomodulatory effects.
• The cellular mechanisms translating physical force into visceral repair are not well understood.
• Identifying the specific cells responsible for mechanotransduction in tissue repair is crucial.

Purpose of the Study:

• To identify the primary mechanosensory cells involved in somatic mechanotherapy-induced visceral repair.
• To elucidate the molecular pathways linking peripheral mechanical stimulation to systemic regeneration.
• To define the role of these cells in reprogramming inflammatory responses to regenerative ones.

Main Methods:

• Utilized a custom interpretable deep learning framework (CARSS) on single-cell RNA sequencing data.
• Investigated CD34+PDGFRα+ telocytes (CPTCs) in fascial and colonic tissues during bacterial colitis.
• Analyzed transcriptional programs, including AP-1/Hsp70 and Wnt signaling pathways.

Main Results:

• Identified CD34+PDGFRα+ telocytes (CPTCs) as key mechanosensors in fascia and colon.
• Demonstrated that somatic mechanotherapy activates a specific transcriptional program in fascial CPTCs, leading to systemic Wnt elevation.
• Showed that this Wnt elevation induces 'transcriptional resonance' in colonic CPTCs, shifting them from inflammation to regeneration.
• Revealed activation of epithelial β-catenin/Myc signaling, suppressing apoptosis and restoring barrier integrity.

Conclusions:

• Defined the CPTC-Driven Mechano-Resonance Axis, a novel pathway for somatic mechanotherapy.
• CPTCs act as synchronized relay stations, converting mechanical stimuli into systemic regenerative environments.
• This axis facilitates tissue repair and barrier restoration independently of immune cell modulation.