Canonical Wnt signaling directs the generation of functional human PSC-derived atrioventricular canal cardiomyocytes in bioprinted cardiac tissues

Cell Stem Cell. 2024 Mar 7;31(3):398-409.e5. doi: 10.1016/j.stem.2024.01.008. Epub 2024 Feb 15.

Abstract

The creation of a functional 3D bioprinted human heart remains challenging, largely due to the lack of some crucial cardiac cell types, including the atrioventricular canal (AVC) cardiomyocytes, which are essential to slow down the electrical impulse between the atrium and ventricle. By utilizing single-cell RNA sequencing analysis and a 3D bioprinting technology, we discover that stage-specific activation of canonical Wnt signaling creates functional AVC cardiomyocytes derived from human pluripotent stem cells. These cardiomyocytes display morphological characteristics and express molecular markers of AVC cardiomyocytes, including transcription factors TBX2 and MSX2. When bioprinted in prefabricated cardiac tissues, these cardiomyocytes successfully delay the electrical impulse, demonstrating their capability of functioning as the AVC cardiomyocytes in vitro. Thus, these findings not only identify canonical Wnt signaling as a key regulator of the AVC cardiomyocyte differentiation in vitro, but, more importantly, provide a critical cellular source for the biofabrication of a functional human heart.

Keywords: 3D bioprinting; atrioventricular canal cardiomyocytes; canonical Wnt signaling; differentiation; human pluripotent stem cells; single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Endocardial Cushions
  • Heart Septal Defects*
  • Heart Ventricles
  • Humans
  • Myocytes, Cardiac* / metabolism
  • Wnt Signaling Pathway*

Supplementary concepts

  • Complete atrioventricular septal defect