Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells
Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1237176/full |
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| author | Stanley F. Bazarek Mentor Thaqi Mentor Thaqi Patrick King Patrick King Amol R. Mehta Ronil Patel Clark A. Briggs Emily Reisenbigler Emily Reisenbigler Jonathon E. Yousey Jonathon E. Yousey Elis A. Miller Grace E. Stutzmann Grace E. Stutzmann Robert A. Marr Robert A. Marr Daniel A. Peterson Daniel A. Peterson |
| author_facet | Stanley F. Bazarek Mentor Thaqi Mentor Thaqi Patrick King Patrick King Amol R. Mehta Ronil Patel Clark A. Briggs Emily Reisenbigler Emily Reisenbigler Jonathon E. Yousey Jonathon E. Yousey Elis A. Miller Grace E. Stutzmann Grace E. Stutzmann Robert A. Marr Robert A. Marr Daniel A. Peterson Daniel A. Peterson |
| author_sort | Stanley F. Bazarek |
| collection | DOAJ |
| description | Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo. Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry. |
| first_indexed | 2024-03-12T14:28:22Z |
| format | Article |
| id | doaj.art-73fb503078e64d9f8f65f691539b2b12 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-12T14:28:22Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-73fb503078e64d9f8f65f691539b2b122023-08-17T22:04:39ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-08-011710.3389/fnins.2023.12371761237176Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cellsStanley F. Bazarek0Mentor Thaqi1Mentor Thaqi2Patrick King3Patrick King4Amol R. Mehta5Ronil Patel6Clark A. Briggs7Emily Reisenbigler8Emily Reisenbigler9Jonathon E. Yousey10Jonathon E. Yousey11Elis A. Miller12Grace E. Stutzmann13Grace E. Stutzmann14Robert A. Marr15Robert A. Marr16Daniel A. Peterson17Daniel A. Peterson18Center for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Neurodegenerative Disease and Therapeutics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Neurodegenerative Disease and Therapeutics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Neurodegenerative Disease and Therapeutics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Neurodegenerative Disease and Therapeutics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Neurodegenerative Disease and Therapeutics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Neurodegenerative Disease and Therapeutics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Neurodegenerative Disease and Therapeutics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Stem Cell and Regenerative Medicine, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesCenter for Neurodegenerative Disease and Therapeutics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesAdult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo. Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry.https://www.frontiersin.org/articles/10.3389/fnins.2023.1237176/fulloligodendrocyte precursor cellNeuroD1 transcription factorNeurogenin 2NG2 cellreprogramming and differentiationneuronal replacement |
| spellingShingle | Stanley F. Bazarek Mentor Thaqi Mentor Thaqi Patrick King Patrick King Amol R. Mehta Ronil Patel Clark A. Briggs Emily Reisenbigler Emily Reisenbigler Jonathon E. Yousey Jonathon E. Yousey Elis A. Miller Grace E. Stutzmann Grace E. Stutzmann Robert A. Marr Robert A. Marr Daniel A. Peterson Daniel A. Peterson Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells Frontiers in Neuroscience oligodendrocyte precursor cell NeuroD1 transcription factor Neurogenin 2 NG2 cell reprogramming and differentiation neuronal replacement |
| title | Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells |
| title_full | Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells |
| title_fullStr | Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells |
| title_full_unstemmed | Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells |
| title_short | Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells |
| title_sort | engineered neurogenesis in naive adult rat cortex by ngn2 mediated neuronal reprogramming of resident oligodendrocyte progenitor cells |
| topic | oligodendrocyte precursor cell NeuroD1 transcription factor Neurogenin 2 NG2 cell reprogramming and differentiation neuronal replacement |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1237176/full |
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