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Transcriptional Targets of TWIST1 in Human Mesenchymal Stem/Stromal Cells Mechanistically Link Stem/Progenitor and

Christopher L Haga1, Cori N Booker1, Ana Carvalho1

  • 1The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Department of Molecular Medicine, Jupiter, FL, USA.

Stem Cells (Dayton, Ohio)
|September 4, 2023
PubMed

Insights

TWIST1 is a key regulator of mesenchymal stem/stromal cell (MSC) potency. Identifying TWIST1 targets reveals its role in MSC function, potentially improving cell therapies.

Area of Science:

  • Stem Cell Biology
  • Regenerative Medicine
  • Molecular Biology

Background:

  • Mesenchymal stem/stromal cell (MSC) therapies show limited efficacy due to a lack of potency biomarkers.
  • Previous research identified TWIST1 as a predictor of MSC quality and potency.

Purpose of the Study:

  • To comprehensively define the full range of TWIST1 activity in MSCs.
  • To identify novel TWIST1 target genes and associated cellular processes.

Main Methods:

  • Integrated omics-based profiling was employed to identify high-confidence TWIST1 targets.
  • Bioinformatic analysis mapped identified targets to specific cellular functions and pathways.

Main Results:

  • A set of TWIST1 targets was identified, involved in extracellular matrix (ECM) organization, skeletal and circulatory development, and inflammatory signaling.
  • These targets link TWIST1 to both stem/progenitor and paracrine functions of MSCs.
  • TWIST1's role in modulating cellular responses to niche remodeling via ECM dynamics was highlighted.

Conclusions:

  • TWIST1 is a crucial regulator of multiple MSC functions, including stemness, paracrine activity, and response to niche.
  • The identified TWIST1 targets provide a basis for future research into MSC potency and therapeutic applications.
  • Understanding TWIST1-mediated pathways can lead to improved MSC-based therapies.
Keywords:
ChIP-SeqE-box elementsRNA-SeqTWIST1biomarkersbone marrow mesenchymal stem cellsmesenchymal stromal cells

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