Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells
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 funct...
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2025-01-01
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| author | Sasi Kumar Jagadeesan Ahmad Galuta Ryan Vimukthi Sandarage Eve Chung Tsai |
| author_facet | Sasi Kumar Jagadeesan Ahmad Galuta Ryan Vimukthi Sandarage Eve Chung Tsai |
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| description | 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. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-c91afbe341d34607b2f90638f9a2e2992025-01-24T13:26:32ZengMDPI AGCells2073-44092025-01-011426410.3390/cells14020064Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor CellsSasi Kumar Jagadeesan0Ahmad Galuta1Ryan Vimukthi Sandarage2Eve Chung Tsai3Department of Neurosciences, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, CanadaDepartment of Neurosciences, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, CanadaDivision of Neurosurgery, Department of Surgery, The Ottawa Hospital, Ottawa, ON K1H 8L6, CanadaDepartment of Neurosciences, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, CanadaThe 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.https://www.mdpi.com/2073-4409/14/2/64spinal cord injuryneural stem/progenitor cellsinduced pluripotent stem cellstranscriptomicsneurogenesisdifferentiation potential |
| spellingShingle | Sasi Kumar Jagadeesan Ahmad Galuta Ryan Vimukthi Sandarage Eve Chung Tsai Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells Cells spinal cord injury neural stem/progenitor cells induced pluripotent stem cells transcriptomics neurogenesis differentiation potential |
| title | Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells |
| title_full | Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells |
| title_fullStr | Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells |
| title_full_unstemmed | Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells |
| title_short | Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells |
| title_sort | transcriptomic and functional landscape of adult human spinal cord nspcs compared to ipsc derived neural progenitor cells |
| topic | spinal cord injury neural stem/progenitor cells induced pluripotent stem cells transcriptomics neurogenesis differentiation potential |
| url | https://www.mdpi.com/2073-4409/14/2/64 |
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