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

## TL;DR

This study uses single-cell RNA sequencing to show how neural stem cells can transform into heart-like cells when placed in a heart extracellular matrix scaffold.

## Contribution

The study identifies specific cell subpopulations and dual lineage signatures during neural stem cell trans-differentiation into cardiac lineage cells.

## Key findings

- Neural stem cells can trans-differentiate into cardiac lineage cells while retaining their neural differentiation potential.
- Trans-differentiated heart-like cells exhibit dual signatures of neuroectoderm and cardiac mesoderm.
- The whole heart decellularized extracellular matrix supports cellular diversity in recellularization.

## 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.