Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors
Summary: Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons...
Ausführliche Beschreibung
Autor*in: |
Levi Todd [verfasserIn] Marcus J. Hooper [verfasserIn] Alexandra K. Haugan [verfasserIn] Connor Finkbeiner [verfasserIn] Nikolas Jorstad [verfasserIn] Nicholas Radulovich [verfasserIn] Claire K. Wong [verfasserIn] Phoebe C. Donaldson [verfasserIn] Wesley Jenkins [verfasserIn] Qiang Chen [verfasserIn] Fred Rieke [verfasserIn] Thomas A. Reh [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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In: Cell Reports - Elsevier, 2015, 37(2021), 3, Seite 109857- |
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Übergeordnetes Werk: |
volume:37 ; year:2021 ; number:3 ; pages:109857- |
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DOI / URN: |
10.1016/j.celrep.2021.109857 |
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Katalog-ID: |
DOAJ054748054 |
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245 | 1 | 0 | |a Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors |
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520 | |a Summary: Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons in the adult mouse retina. However, this process is inefficient, and only a third of the Ascl1-expressing MG generate new neurons. Here, we test whether proneural transcription factors of the Atoh1/7 class can further promote the regenerative capacity of MG. We find that the combination of Ascl1:Atoh1 is remarkably efficient at stimulating neurogenesis, even in the absence of retinal injury. Using electrophysiology and single-cell RNA sequencing (scRNA-seq), we demonstrate that Ascl1:Atoh1 generates a diversity of retinal neuron types, with the majority expressing characteristics of retinal ganglion cells. Our results provide a proof of principle that combinations of developmental transcription factors can substantially improve glial reprogramming to neurons and expand the repertoire of regenerated cell fates. | ||
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10.1016/j.celrep.2021.109857 doi (DE-627)DOAJ054748054 (DE-599)DOAJ4e22db68d209415691d36918e753da31 DE-627 ger DE-627 rakwb eng QH301-705.5 Levi Todd verfasserin aut Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons in the adult mouse retina. However, this process is inefficient, and only a third of the Ascl1-expressing MG generate new neurons. Here, we test whether proneural transcription factors of the Atoh1/7 class can further promote the regenerative capacity of MG. We find that the combination of Ascl1:Atoh1 is remarkably efficient at stimulating neurogenesis, even in the absence of retinal injury. Using electrophysiology and single-cell RNA sequencing (scRNA-seq), we demonstrate that Ascl1:Atoh1 generates a diversity of retinal neuron types, with the majority expressing characteristics of retinal ganglion cells. Our results provide a proof of principle that combinations of developmental transcription factors can substantially improve glial reprogramming to neurons and expand the repertoire of regenerated cell fates. retina glia regeneration reprogramming bHLH transcription factors Muller glia Biology (General) Marcus J. Hooper verfasserin aut Alexandra K. Haugan verfasserin aut Connor Finkbeiner verfasserin aut Nikolas Jorstad verfasserin aut Nicholas Radulovich verfasserin aut Claire K. Wong verfasserin aut Phoebe C. Donaldson verfasserin aut Wesley Jenkins verfasserin aut Qiang Chen verfasserin aut Fred Rieke verfasserin aut Thomas A. Reh verfasserin aut In Cell Reports Elsevier, 2015 37(2021), 3, Seite 109857- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:37 year:2021 number:3 pages:109857- https://doi.org/10.1016/j.celrep.2021.109857 kostenfrei https://doaj.org/article/4e22db68d209415691d36918e753da31 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124721013243 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 37 2021 3 109857- |
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10.1016/j.celrep.2021.109857 doi (DE-627)DOAJ054748054 (DE-599)DOAJ4e22db68d209415691d36918e753da31 DE-627 ger DE-627 rakwb eng QH301-705.5 Levi Todd verfasserin aut Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons in the adult mouse retina. However, this process is inefficient, and only a third of the Ascl1-expressing MG generate new neurons. Here, we test whether proneural transcription factors of the Atoh1/7 class can further promote the regenerative capacity of MG. We find that the combination of Ascl1:Atoh1 is remarkably efficient at stimulating neurogenesis, even in the absence of retinal injury. Using electrophysiology and single-cell RNA sequencing (scRNA-seq), we demonstrate that Ascl1:Atoh1 generates a diversity of retinal neuron types, with the majority expressing characteristics of retinal ganglion cells. Our results provide a proof of principle that combinations of developmental transcription factors can substantially improve glial reprogramming to neurons and expand the repertoire of regenerated cell fates. retina glia regeneration reprogramming bHLH transcription factors Muller glia Biology (General) Marcus J. Hooper verfasserin aut Alexandra K. Haugan verfasserin aut Connor Finkbeiner verfasserin aut Nikolas Jorstad verfasserin aut Nicholas Radulovich verfasserin aut Claire K. Wong verfasserin aut Phoebe C. Donaldson verfasserin aut Wesley Jenkins verfasserin aut Qiang Chen verfasserin aut Fred Rieke verfasserin aut Thomas A. Reh verfasserin aut In Cell Reports Elsevier, 2015 37(2021), 3, Seite 109857- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:37 year:2021 number:3 pages:109857- https://doi.org/10.1016/j.celrep.2021.109857 kostenfrei https://doaj.org/article/4e22db68d209415691d36918e753da31 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124721013243 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 37 2021 3 109857- |
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10.1016/j.celrep.2021.109857 doi (DE-627)DOAJ054748054 (DE-599)DOAJ4e22db68d209415691d36918e753da31 DE-627 ger DE-627 rakwb eng QH301-705.5 Levi Todd verfasserin aut Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons in the adult mouse retina. However, this process is inefficient, and only a third of the Ascl1-expressing MG generate new neurons. Here, we test whether proneural transcription factors of the Atoh1/7 class can further promote the regenerative capacity of MG. We find that the combination of Ascl1:Atoh1 is remarkably efficient at stimulating neurogenesis, even in the absence of retinal injury. Using electrophysiology and single-cell RNA sequencing (scRNA-seq), we demonstrate that Ascl1:Atoh1 generates a diversity of retinal neuron types, with the majority expressing characteristics of retinal ganglion cells. Our results provide a proof of principle that combinations of developmental transcription factors can substantially improve glial reprogramming to neurons and expand the repertoire of regenerated cell fates. retina glia regeneration reprogramming bHLH transcription factors Muller glia Biology (General) Marcus J. Hooper verfasserin aut Alexandra K. Haugan verfasserin aut Connor Finkbeiner verfasserin aut Nikolas Jorstad verfasserin aut Nicholas Radulovich verfasserin aut Claire K. Wong verfasserin aut Phoebe C. Donaldson verfasserin aut Wesley Jenkins verfasserin aut Qiang Chen verfasserin aut Fred Rieke verfasserin aut Thomas A. Reh verfasserin aut In Cell Reports Elsevier, 2015 37(2021), 3, Seite 109857- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:37 year:2021 number:3 pages:109857- https://doi.org/10.1016/j.celrep.2021.109857 kostenfrei https://doaj.org/article/4e22db68d209415691d36918e753da31 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124721013243 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 37 2021 3 109857- |
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10.1016/j.celrep.2021.109857 doi (DE-627)DOAJ054748054 (DE-599)DOAJ4e22db68d209415691d36918e753da31 DE-627 ger DE-627 rakwb eng QH301-705.5 Levi Todd verfasserin aut Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons in the adult mouse retina. However, this process is inefficient, and only a third of the Ascl1-expressing MG generate new neurons. Here, we test whether proneural transcription factors of the Atoh1/7 class can further promote the regenerative capacity of MG. We find that the combination of Ascl1:Atoh1 is remarkably efficient at stimulating neurogenesis, even in the absence of retinal injury. Using electrophysiology and single-cell RNA sequencing (scRNA-seq), we demonstrate that Ascl1:Atoh1 generates a diversity of retinal neuron types, with the majority expressing characteristics of retinal ganglion cells. Our results provide a proof of principle that combinations of developmental transcription factors can substantially improve glial reprogramming to neurons and expand the repertoire of regenerated cell fates. retina glia regeneration reprogramming bHLH transcription factors Muller glia Biology (General) Marcus J. Hooper verfasserin aut Alexandra K. Haugan verfasserin aut Connor Finkbeiner verfasserin aut Nikolas Jorstad verfasserin aut Nicholas Radulovich verfasserin aut Claire K. Wong verfasserin aut Phoebe C. Donaldson verfasserin aut Wesley Jenkins verfasserin aut Qiang Chen verfasserin aut Fred Rieke verfasserin aut Thomas A. Reh verfasserin aut In Cell Reports Elsevier, 2015 37(2021), 3, Seite 109857- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:37 year:2021 number:3 pages:109857- https://doi.org/10.1016/j.celrep.2021.109857 kostenfrei https://doaj.org/article/4e22db68d209415691d36918e753da31 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124721013243 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 37 2021 3 109857- |
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Levi Todd @@aut@@ Marcus J. Hooper @@aut@@ Alexandra K. Haugan @@aut@@ Connor Finkbeiner @@aut@@ Nikolas Jorstad @@aut@@ Nicholas Radulovich @@aut@@ Claire K. Wong @@aut@@ Phoebe C. Donaldson @@aut@@ Wesley Jenkins @@aut@@ Qiang Chen @@aut@@ Fred Rieke @@aut@@ Thomas A. Reh @@aut@@ |
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Levi Todd misc QH301-705.5 misc retina misc glia misc regeneration misc reprogramming misc bHLH transcription factors misc Muller glia misc Biology (General) Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors |
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QH301-705.5 Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors retina glia regeneration reprogramming bHLH transcription factors Muller glia |
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Levi Todd Marcus J. Hooper Alexandra K. Haugan Connor Finkbeiner Nikolas Jorstad Nicholas Radulovich Claire K. Wong Phoebe C. Donaldson Wesley Jenkins Qiang Chen Fred Rieke Thomas A. Reh |
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efficient stimulation of retinal regeneration from müller glia in adult mice using combinations of proneural bhlh transcription factors |
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Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors |
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Summary: Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons in the adult mouse retina. However, this process is inefficient, and only a third of the Ascl1-expressing MG generate new neurons. Here, we test whether proneural transcription factors of the Atoh1/7 class can further promote the regenerative capacity of MG. We find that the combination of Ascl1:Atoh1 is remarkably efficient at stimulating neurogenesis, even in the absence of retinal injury. Using electrophysiology and single-cell RNA sequencing (scRNA-seq), we demonstrate that Ascl1:Atoh1 generates a diversity of retinal neuron types, with the majority expressing characteristics of retinal ganglion cells. Our results provide a proof of principle that combinations of developmental transcription factors can substantially improve glial reprogramming to neurons and expand the repertoire of regenerated cell fates. |
abstractGer |
Summary: Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons in the adult mouse retina. However, this process is inefficient, and only a third of the Ascl1-expressing MG generate new neurons. Here, we test whether proneural transcription factors of the Atoh1/7 class can further promote the regenerative capacity of MG. We find that the combination of Ascl1:Atoh1 is remarkably efficient at stimulating neurogenesis, even in the absence of retinal injury. Using electrophysiology and single-cell RNA sequencing (scRNA-seq), we demonstrate that Ascl1:Atoh1 generates a diversity of retinal neuron types, with the majority expressing characteristics of retinal ganglion cells. Our results provide a proof of principle that combinations of developmental transcription factors can substantially improve glial reprogramming to neurons and expand the repertoire of regenerated cell fates. |
abstract_unstemmed |
Summary: Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons in the adult mouse retina. However, this process is inefficient, and only a third of the Ascl1-expressing MG generate new neurons. Here, we test whether proneural transcription factors of the Atoh1/7 class can further promote the regenerative capacity of MG. We find that the combination of Ascl1:Atoh1 is remarkably efficient at stimulating neurogenesis, even in the absence of retinal injury. Using electrophysiology and single-cell RNA sequencing (scRNA-seq), we demonstrate that Ascl1:Atoh1 generates a diversity of retinal neuron types, with the majority expressing characteristics of retinal ganglion cells. Our results provide a proof of principle that combinations of developmental transcription factors can substantially improve glial reprogramming to neurons and expand the repertoire of regenerated cell fates. |
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Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors |
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