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

Sasi Kumar Jagadeesan; Ahmad Galuta; Ryan Vimukthi Sandarage; Eve Chung Tsai

doi:10.3390/cells14020064

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

Cells. 2025 Jan 7;14(2):64. doi: 10.3390/cells14020064.

Authors

Sasi Kumar Jagadeesan^{1

2}, Ahmad Galuta^{1

2}, Ryan Vimukthi Sandarage³, Eve Chung Tsai^{1

2

3}

Affiliations

¹ Department of Neurosciences, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
² Neuroscience Program, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1Y 4E9, Canada.
³ Division of Neurosurgery, Department of Surgery, The Ottawa Hospital, Ottawa, ON K1H 8L6, Canada.

Abstract

The adult human spinal cord harbors diverse populations of neural stem/progenitor cells (NSPCs) essential for neuroregeneration and central nervous system repair. While induced pluripotent stem cell (iPSC)-derived NSPCs offer significant therapeutic potential, understanding their molecular and functional alignment with bona fide spinal cord NSPCs is crucial for developing autologous cell therapies that enhance spinal cord regeneration and minimize immune rejection. In this study, we present 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 close resemblance to bona fide spinal cord NSPCs, characterized by enriched expression of neurogenesis, axon guidance, synaptic signaling, and voltage-gated calcium channel activity pathways. Conversely, iPSC-SC NSPCs displayed significant heterogeneity, suboptimal regional specification, and elevated expression of neural crest and immune response-associated genes. Functional assays corroborated the transcriptomic findings, demonstrating superior neurogenic potential in iPSC-Br NSPCs. Additionally, we assessed donor-specific influences on NSPC behavior by analyzing gene expression and differentiation outcomes across syngeneic populations from multiple individuals. Donor-specific factors significantly modulated transcriptomic profiles, with notable variability in the alignment of iPSC-derived NSPCs to bona fide spinal cord NSPCs. Enrichment of pathways related to neurogenesis, axon guidance, and synaptic signaling varied across donors, highlighting the impact of genetic and epigenetic individuality on NSPC behavior.

Keywords: cellular heterogeneity; differentiation potential; induced pluripotent stem cells; neural stem/progenitor cells; neurogenesis; patient-specific variability; proliferation dynamics; regenerative medicine; spinal cord injury; transcriptomics.

Publication types

Comparative Study

MeSH terms

Adult
Cell Differentiation / genetics
Gene Expression Profiling
Humans
Induced Pluripotent Stem Cells* / cytology
Induced Pluripotent Stem Cells* / metabolism
Neural Stem Cells* / cytology
Neural Stem Cells* / metabolism
Neurogenesis / genetics
Spinal Cord* / cytology
Spinal Cord* / metabolism
Transcriptome* / genetics

Grants and funding

This research was supported by the Josette Robertson and Joan Johnston Family Foundation Fund (Grant No. JRJJ-2024-001), the Michael T. Richard Clinical Research Fellowship in Neurosurgery at the University of Ottawa Brain and Mind Research Institute (Grant No. MTRF-23-567), the Department of Surgery at the University of Ottawa (Grant No. DOS-2024-045), and the Society of Neurological Surgeons, RUNN Course Resident Award (Grant No. RUNN-2024-678).