Single-Cell RNA-Seq Identifies Dynamic Cardiac Transition Program from ADCs Induced by Leukemia Inhibitory Factor

Area of Science:

• Stem cell biology
• Regenerative medicine
• Cardiovascular research

Background:

• Adipose-derived cells (ADCs) show potential for cardiac regeneration due to abundant reserves.
• Low efficiency in ADC-cardiac transition is attributed to cellular heterogeneity and unclear mechanisms.
• Leukemia inhibitory factor (LIF) is investigated as an inducer for ADC cardiomyogenesis.

Purpose of the Study:

• To investigate ADC heterogeneity and cellular kinetics during LIF-induced cardiac transition.
• To elucidate the mechanisms underlying ADC-myogenesis and cell fate determination.
• To identify factors influencing the efficiency of cardiac regeneration from ADCs.

Main Methods:

• Single-cell RNA sequencing of 39,432 ADCs undergoing LIF-induced cardiac transition.
• Analysis of cellular kinetics and gene expression patterns.
• Pseudotime analysis to map cell trajectories and identify distinct cell populations.

Main Results:

• Identified distinct ADC subpopulations with differential responses to LIF during cardiomyogenesis.
• Demonstrated that ADC-myogenesis is time-dependent and initiated by transient Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) signaling.
• Pseudotime analysis revealed two main cell fate trajectories: activated myofibroblasts and cardiomyocyte-like cells.

Conclusions:

• High-resolution insights into ADC heterogeneity and cell fate during cardiac transition.
• Understanding the role of Nrf2 signaling in initiating cardiomyogenesis.
• Provides a foundation for improving cardiac regeneration strategies using ADCs.