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Wnt/BMP Mediated Metabolic Reprogramming Preserves Multipotency of Neural Crest-Like Stem Cells.

Pihu Mehrotra1, Izuagie Ikhapoh1, Pedro Lei1

  • 1Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, NY, USA.

Stem Cells (Dayton, Ohio)
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Summary

Activating Wnt/BMP signaling preserves multipotency in neural crest-like stem cells by linking gene expression to a highly glycolytic metabolism. This finding has implications for regenerative medicine applications.

Keywords:
glycolysislactatemitochondriamultipotencyneural crest cellsβ-catenin

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Area of Science:

  • Stem cell biology
  • Developmental biology
  • Metabolic reprogramming

Background:

  • Adult human tissues can yield neural crest-like stem cells (NCs).
  • These cells rapidly lose multipotency in culture, limiting clinical use.
  • Preserving multipotency is crucial for regenerative medicine.

Purpose of the Study:

  • To investigate methods for preserving multipotency in keratinocyte-derived NCs (KC-NCs).
  • To explore the role of Wnt and BMP signaling in KC-NCs multipotency.
  • To understand the link between metabolic state and stem cell fate.

Main Methods:

  • Activation of Wnt and BMP signaling pathways in KC-NCs.
  • Analysis of gene expression, focusing on NC-specifier genes.
  • Metabolic assays including glucose uptake, lactate production, and ATP measurement.
  • Assessment of mitochondrial function.

Main Results:

  • Wnt and BMP signaling activation preserved KC-NCs multipotency and differentiation potential.
  • Multipotency was associated with a metabolic shift towards glycolysis.
  • Increased glycolysis led to lactate production, which stabilized beta-catenin and enhanced NC-gene expression.
  • Mitochondrial function was altered, with decreased ATP production.

Conclusions:

  • Wnt/BMP signaling activation is key to maintaining KC-NCs multipotency.
  • Metabolic reprogramming to glycolysis is intrinsically linked to stem cell fate decisions.
  • Lactate plays a role in stabilizing key factors for maintaining neural crest characteristics.
  • These findings offer potential strategies for regenerative medicine using stem cells.