Neuron-specific RNA-sequencing reveals different responses in peripheral neurons after nerve injury
Bolívar Martín, Sara (Universitat Autònoma de Barcelona. Institut de Neurociències)
Sanz Iglesias, Elisenda (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Ovelleiro, David (Vall d'Hebron Institut de Recerca (VHIR))
Zochodne, Douglas W. (University of Alberta. Department of Medicine and the Neuroscience and Mental Health Institute)
Udina i Bonet, Esther (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Universitat Autònoma de Barcelona. Institut de Neurociències

Data:	2024
Resum:	Peripheral neurons are heterogeneous and functionally diverse, but all share the capability to switch to a pro-regenerative state after nerve injury. Despite the assumption that the injury response is similar among neuronal subtypes, functional recovery may differ. Understanding the distinct intrinsic regenerative properties between neurons may help to improve the quality of regeneration, prioritizing the growth of axon subpopulations to their targets. Here, we present a comparative analysis of regeneration across four key peripheral neuron populations: motoneurons, proprioceptors, cutaneous mechanoreceptors, and nociceptors. Using Cre/Ai9 mice that allow fluorescent labeling of neuronal subtypes, we found that nociceptors showed the greater regeneration after a sciatic crush, followed by motoneurons, mechanoreceptors, and, finally, proprioceptors. By breeding these Cre mice with Ribotag mice, we isolated specific translatomes and defined the regenerative response of these neuronal subtypes after axotomy. Only 20% of the regulated genes were common, revealing a diverse response to injury among neurons, which was also supported by the differential influence of neurotrophins among neuron subtypes. Among differentially regulated genes, we proposed MED12 as a specific regulator of the regeneration of proprioceptors. Altogether, we demonstrate that the intrinsic regenerative capacity differs between peripheral neuron subtypes, opening the door to selectively modulate these responses.
Ajuts:	Agencia Estatal de Investigación SAF2017-84464-R Ministerio de Ciencia e Innovación FPU17/03657 Agencia Estatal de Investigación PID2021-127626OB-I00
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Nerve injury ; Axon regeneration ; Sensory neuron ; Motorneuron ; RNA-sequencing ; Specific regeneration ; Mouse
Publicat a:	eLife, Vol. 12 (may 2024) , ISSN 2050-084X

DOI: 10.7554/eLife.91316
PMID: 38742628

26 p, 6.5 MB

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