Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury
Summary: Peripheral nerve regeneration after injury requires a broad program of transcriptional changes. We investigated the basis for the enhanced nerve regenerative capacity of the CAST/Ei mouse strain relative to C57BL/6 mice. RNA sequencing of dorsal root ganglia (DRG) showed a CAST/Ei-specific...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717309622 |
| _version_ | 1819043072179175424 |
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| author | Véronique Lisi Bhagat Singh Michel Giroux Elmer Guzman Michio W. Painter Yung-Chih Cheng Eric Huebner Giovanni Coppola Michael Costigan Clifford J. Woolf Kenneth S. Kosik |
| author_facet | Véronique Lisi Bhagat Singh Michel Giroux Elmer Guzman Michio W. Painter Yung-Chih Cheng Eric Huebner Giovanni Coppola Michael Costigan Clifford J. Woolf Kenneth S. Kosik |
| author_sort | Véronique Lisi |
| collection | DOAJ |
| description | Summary: Peripheral nerve regeneration after injury requires a broad program of transcriptional changes. We investigated the basis for the enhanced nerve regenerative capacity of the CAST/Ei mouse strain relative to C57BL/6 mice. RNA sequencing of dorsal root ganglia (DRG) showed a CAST/Ei-specific upregulation of Ascl1 after injury. Ascl1 overexpression in DRG neurons of C57BL/6 mice enhanced their neurite outgrowth. Ascl1 is regulated by miR-7048-3p, which is downregulated in CAST/Ei mice. Inhibition of miR-7048-3p enhances neurite outgrowth. Following injury, CAST/Ei neurons largely retained their mature neuronal profile as determined by single-cell RNA- seq, whereas the C57BL/6 neurons acquired an immature profile. These findings suggest that one facet of the enhanced regenerative phenotype is preservation of neuronal identity in response to injury. : Lisi et al. find that increased Ascl1 expression is associated with the superior regenerative capacity of CAST/Ei mice. Single-cell RNA-seq demonstrated that CAST/Ei mice retained more mature neurons after injury than did C57BL/6 mice, thereby suggesting that genetic drivers of the enhanced regenerative phenotype include mechanisms to preserve neuronal identity after injury. Keywords: single-cell analyses, RNA sequencing, regeneration, dorsal root ganglia, CAST/Ei, Ascl1, miR-7048 |
| first_indexed | 2024-12-21T09:50:58Z |
| format | Article |
| id | doaj.art-a39f43325083432fa937c1852723fffe |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T09:50:58Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a39f43325083432fa937c1852723fffe2022-12-21T19:08:11ZengElsevierCell Reports2211-12472017-08-0120511361147Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after InjuryVéronique Lisi0Bhagat Singh1Michel Giroux2Elmer Guzman3Michio W. Painter4Yung-Chih Cheng5Eric Huebner6Giovanni Coppola7Michael Costigan8Clifford J. Woolf9Kenneth S. Kosik10Department of Molecular, Cellular, and Developmental Biology, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USAF.M. Kirby Neurobiology Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USADepartment of Molecular, Cellular, and Developmental Biology, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USADepartment of Molecular, Cellular, and Developmental Biology, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USAF.M. Kirby Neurobiology Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USAF.M. Kirby Neurobiology Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USAF.M. Kirby Neurobiology Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USADepartments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USAF.M. Kirby Neurobiology Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA; Anaesthesia Department, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USAF.M. Kirby Neurobiology Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USADepartment of Molecular, Cellular, and Developmental Biology, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Corresponding authorSummary: Peripheral nerve regeneration after injury requires a broad program of transcriptional changes. We investigated the basis for the enhanced nerve regenerative capacity of the CAST/Ei mouse strain relative to C57BL/6 mice. RNA sequencing of dorsal root ganglia (DRG) showed a CAST/Ei-specific upregulation of Ascl1 after injury. Ascl1 overexpression in DRG neurons of C57BL/6 mice enhanced their neurite outgrowth. Ascl1 is regulated by miR-7048-3p, which is downregulated in CAST/Ei mice. Inhibition of miR-7048-3p enhances neurite outgrowth. Following injury, CAST/Ei neurons largely retained their mature neuronal profile as determined by single-cell RNA- seq, whereas the C57BL/6 neurons acquired an immature profile. These findings suggest that one facet of the enhanced regenerative phenotype is preservation of neuronal identity in response to injury. : Lisi et al. find that increased Ascl1 expression is associated with the superior regenerative capacity of CAST/Ei mice. Single-cell RNA-seq demonstrated that CAST/Ei mice retained more mature neurons after injury than did C57BL/6 mice, thereby suggesting that genetic drivers of the enhanced regenerative phenotype include mechanisms to preserve neuronal identity after injury. Keywords: single-cell analyses, RNA sequencing, regeneration, dorsal root ganglia, CAST/Ei, Ascl1, miR-7048http://www.sciencedirect.com/science/article/pii/S2211124717309622 |
| spellingShingle | Véronique Lisi Bhagat Singh Michel Giroux Elmer Guzman Michio W. Painter Yung-Chih Cheng Eric Huebner Giovanni Coppola Michael Costigan Clifford J. Woolf Kenneth S. Kosik Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury Cell Reports |
| title | Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury |
| title_full | Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury |
| title_fullStr | Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury |
| title_full_unstemmed | Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury |
| title_short | Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury |
| title_sort | enhanced neuronal regeneration in the cast ei mouse strain is linked to expression of differentiation markers after injury |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717309622 |
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