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Identification of Key Factors Regulating Self-renewal and Differentiation in EML Hematopoietic Precursor Cells by RNA-sequencing Analysis
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Single-Cell RNA-Seq Identifies Dynamic Cardiac Transition Program from ADCs Induced by Leukemia Inhibitory Factor.

Jiayi Yao1, Feiyang Ma2,3, Li Zhang1

  • 1Division of Cardiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.

Stem Cells (Dayton, Ohio)
|July 27, 2022
PubMed
Summary
This summary is machine-generated.

Leukemia inhibitory factor (LIF) induces cardiac transition in adipose-derived cells (ADCs). This study reveals distinct ADC subpopulations and a time-dependent process involving Nrf2 signaling, leading to cardiomyocyte-like cells.

Keywords:
ADCadiposecardiac transitioncell sequencingderived cellsleukemia inhibitory factor (LIF)single

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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.