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  4. Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells

Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells

Cells, 2025 · DOI: 10.3390/cells14020064 · Published: January 7, 2025

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

This study compares neural stem/progenitor cells (NSPCs) from adult human spinal cords with those derived from induced pluripotent stem cells (iPSCs). The goal is to understand how well iPSC-derived NSPCs mimic real spinal cord NSPCs, which is important for developing cell therapies for spinal cord injuries. Researchers looked at the transcriptomic profiles (gene activity) and functional properties of three types of NSPCs: those directly from the spinal cord, those made from iPSCs and directed to become spinal cord cells (iPSC-SC), and those made from iPSCs and directed to become forebrain cells (iPSC-Br). The study found that iPSC-Br NSPCs were more similar to real spinal cord NSPCs in terms of gene activity and their ability to turn into neurons. This suggests that iPSC-Br NSPCs could be a better option for cell therapies aimed at repairing spinal cord injuries.

Study Duration
Not specified
Participants
Five adult human donors
Evidence Level
Not specified

Key Findings

  • 1
    iPSC-Br NSPCs exhibit a closer resemblance to bona fide spinal cord NSPCs, characterized by enriched expression of neurogenesis, axon guidance, synaptic signaling, and voltage-gated calcium channel activity pathways.
  • 2
    iPSC-SC NSPCs displayed significant heterogeneity, suboptimal regional specification, and elevated expression of neural crest and immune response-associated genes.
  • 3
    Donor-specific factors significantly modulated transcriptomic profiles, with notable variability in the alignment of iPSC-derived NSPCs to bona fide spinal cord NSPCs.

Research Summary

This study provides the first direct transcriptomic and functional comparison of syngeneic adult human NSPC populations, including bona fide spinal cord NSPCs and iPSC-derived NSPCs regionalized to the spinal cord (iPSC-SC) and forebrain (iPSC-Br). RNA sequencing analysis revealed distinct transcriptomic profiles and functional disparities among NSPC types; iPSC-Br NSPCs exhibited a closer resemblance to bona fide spinal cord NSPCs, while iPSC-SC NSPCs displayed significant heterogeneity and suboptimal regional specification. Donor-specific factors significantly modulated transcriptomic profiles, highlighting the impact of genetic and epigenetic individuality on NSPC behavior.

Practical Implications

Regenerative Medicine

iPSC-Br NSPCs show promise as a cell source for autologous therapies targeting spinal cord regeneration due to their transcriptomic similarity to bona fide spinal cord NSPCs.

Personalized Therapies

Donor-specific variability highlights the need for individualized approaches in stem cell therapy development, considering genetic and epigenetic factors.

Neural Biology Research

The distinct transcriptomic profiles of iPSC-SC and iPSC-Br NSPCs provide valuable insights into neural differentiation and regional specification, aiding in understanding neural development.

Study Limitations

  • 1
    Variability in differentiation outcomes of iPSC-derived NSPCs
  • 2
    Residual traits linked to pluripotency in iPSC-derived NSPCs
  • 3
    Challenges in fully replicating the spinal cord microenvironment in vitro

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