Lin28 reprograms inner ear glia to a neuronal fate

Sensorineural hearing loss is irreversible and can be caused by loss of auditory neurons. Regeneration of neural cells from endogenous cells may offer a future tool to restore the auditory circuit and to enhance the performance of implantable hearing devices. Neurons and glial cells in the periphera...

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Vydané v:Stem cells (Dayton, Ohio) Ročník 38; číslo 7; s. 890 - 903
Hlavní autori: Kempfle, Judith S., Luu, Ngoc‐Nhi C., Petrillo, Marco, Al‐Asad, Reef, Zhang, Andrea, Edge, Albert S. B.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Hoboken, USA John Wiley & Sons, Inc 01.07.2020
Oxford University Press
Predmet:
Animals
Brain damage
Brain stem
Cell proliferation
Circuits
Cochlea
Conversion
Ear
Ear, Inner - physiology
Glial cells
glial conversion
Hearing
Hearing aids
Hearing loss
Hearing Loss, Central - metabolism
Hearing protection
Immunohistochemistry
Inner ear
Markers
Mice
mouse models
Myelin proteolipid protein
Nervous system
Neural Stem Cells
Neuroglia - metabolism
Neuronal-glial interactions
Neurons
Neurons - metabolism
Ouabain
Peripheral nervous system
Peripheral neuropathy
Progenitor cells
Regeneration
Stem cells
Surgical implants
Transgenic mice
mouse models
glial conversion
inner ear
neural stem cells
regeneration
ISSN:1066-5099, 1549-4918, 1549-4918
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Shrnutí:Sensorineural hearing loss is irreversible and can be caused by loss of auditory neurons. Regeneration of neural cells from endogenous cells may offer a future tool to restore the auditory circuit and to enhance the performance of implantable hearing devices. Neurons and glial cells in the peripheral nervous system are closely related and originate from a common progenitor. Prior work in our lab indicated that in the early postnatal mouse inner ear, proteolipid protein 1 (Plp1) expressing glial cells could act as progenitor cells for neurons in vitro. Here, we used a transgenic mouse model to transiently overexpress Lin28, a neural stem cell regulator, in Plp1‐positive glial cells. Lin28 promoted proliferation and conversion of auditory glial cells into neurons in vitro. To study the effects of Lin28 on endogenous glial cells after loss of auditory neurons in vivo, we produced a model of auditory neuropathy by selectively damaging auditory neurons with ouabain. After neural damage was confirmed by the auditory brainstem response, we briefly upregulated the Lin28 in Plp1‐expressing inner ear glial cells. One month later, we analyzed the cochlea for neural marker expression by quantitative RT‐PCR and immunohistochemistry. We found that transient Lin28 overexpression in Plp1‐expressing glial cells induced expression of neural stem cell markers and subsequent conversion into neurons. This suggests the potential for inner ear glia to be converted into neurons as a regeneration therapy for neural replacement in auditory neuropathy. We have shown here for the first time that transient upregulation of Lin28 can reprogram Plp1 positive inner ear glial cells into neurons in vitro and in vivo in a mouse model of auditory neuropathy.
Bibliografia:Funding information
National Institutes of Health, Grant/Award Number: DC007174
Judith S. Kempfle and Ngoc‐Nhi C. Luu contributed equally to this study.
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ISSN:1066-5099
1549-4918
1549-4918
DOI:10.1002/stem.3181