Single-cell transcriptomics reveals neural stem cell trans-differentiation and cell subpopulations in whole heart decellularized extracellular matrix

Abstract

The whole heart decellularized extracellular matrix (ECM) has become a promising scaffold material for cardiac tissue engineering. Our previous research has shown that the whole heart acellular matrix possesses the memory function regulating neural stem cells (NSCs) trans-differentiating to cardiac lineage cells. However, the cell subpopulations and phenotypes in the trans-differentiation of NSCs have not been clearly identified. Here, we performed single-cell RNA sequencing and identified 2,765 cells in the recellularized heart with NSCs revealing the cellular diversity of cardiac and neural lineage, confirming NSCs were capable of trans-differentiating into the cardiac lineage while maintaining the original ability to differentiate into the neural lineage. Notably, the trans-differentiated heart-like cells have dual signatures of neuroectoderm and cardiac mesoderm. This study unveils an in-depth mechanism underlying the trans-differentiation of NSCs and provides a new opportunity and theoretical basis for cardiac regeneration.

Graphical abstract

Keywords

Single-cell transcriptomics / Neural stem cell / Trans-differentiation / Decellularized extracellular matrix / Cardiac lineage cells

Acknowledgements

This work was financially supported by Youth Talent Fund Project of Military Medical Research Institute (AMMS-QNPY-2021-005), the Joint Fund Project of the National Natural Science Foundation of China (U21A20394) and National Natural Science Foundation of China Youth Fund (32201116).

RIGHTS & PERMISSIONS

2024 The Author(s)