3 ms·

Ganglion cells created in mice in bid to fix diseased eyes

1 points by mdp2021 4y ago

mdp2021 4y ago
> While fish, reptiles and even some birds can regenerate damaged brain, eye and spinal cord cells, mammals cannot. For the first time, non-neuronal cells have been induced to mimic specific ganglion cells in the eyes of mice > [Researchers] had previously shown that neurons could be coaxed from glial cells in the retinal tissue of mice. Now they've refined the process to produce specific cells[, attempting to produce those types affected by neurodegenerative diseases] > [Having] studied... transcription factors [- proteins that bind to DNA and regulate the activity of genes to control the production of proteins that determine a cell's structure and function -] in vertebrates... that have regenerative abilities[, they] learned how to use the transcription factors to return the glia to a more primitive state known as a progenitor cell [which can be then pushed in other directions - e.g. the retinal ganglion cells lost to glaucoma, or the dopamine neurons which die under Parkinson's] Original research article: Levi Todd et al, Reprogramming Müller glia to regenerate ganglion-like cells in adult mouse retina with developmental transcription factors - https://dx.doi.org/10.1126/sciadv.abq7219 https://dx.doi.org/10.1126/sciadv.abq7219 > Many neurodegenerative diseases cause degeneration of specific types of neurons. For example, glaucoma leads to death of retinal ganglion cells, leaving other neurons intact. Neurons are not regenerated in the adult mammalian central nervous system. However, in nonmammalian vertebrates, glial cells spontaneously reprogram into neural progenitors and replace neurons after injury. We have recently developed strategies to stimulate regeneration of functional neurons in the adult mouse retina by overexpressing the proneural factor Ascl1 in Müller glia. Here, we test additional transcription factors (TFs) for their ability to direct regeneration to particular types of retinal neurons. We engineered mice to express different combinations of TFs in Müller glia, including Ascl1, Pou4f2, Islet1, and Atoh1. Using immunohistochemistry, single-cell RNA sequencing, single-cell assay for transposase-accessible chromatin sequencing, and electrophysiology, we find that retinal ganglion–like cells can be regenerated in the damaged adult mouse retina in vivo with targeted overexpression of developmental retinal ganglion cell TFs

1 points by mdp2021 4y ago

mdp2021 4y ago

> While fish, reptiles and even some birds can regenerate damaged brain, eye and spinal cord cells, mammals cannot. For the first time, non-neuronal cells have been induced to mimic specific ganglion cells in the eyes of mice > [Researchers] had previously shown that neurons could be coaxed from glial cells in the retinal tissue of mice. Now they've refined the process to produce specific cells[, attempting to produce those types affected by neurodegenerative diseases] > [Having] studied... transcription factors [- proteins that bind to DNA and regulate the activity of genes to control the production of proteins that determine a cell's structure and function -] in vertebrates... that have regenerative abilities[, they] learned how to use the transcription factors to return the glia to a more primitive state known as a progenitor cell [which can be then pushed in other directions - e.g. the retinal ganglion cells lost to glaucoma, or the dopamine neurons which die under Parkinson's] Original research article: Levi Todd et al, Reprogramming Müller glia to regenerate ganglion-like cells in adult mouse retina with developmental transcription factors - https://dx.doi.org/10.1126/sciadv.abq7219 https://dx.doi.org/10.1126/sciadv.abq7219 > Many neurodegenerative diseases cause degeneration of specific types of neurons. For example, glaucoma leads to death of retinal ganglion cells, leaving other neurons intact. Neurons are not regenerated in the adult mammalian central nervous system. However, in nonmammalian vertebrates, glial cells spontaneously reprogram into neural progenitors and replace neurons after injury. We have recently developed strategies to stimulate regeneration of functional neurons in the adult mouse retina by overexpressing the proneural factor Ascl1 in Müller glia. Here, we test additional transcription factors (TFs) for their ability to direct regeneration to particular types of retinal neurons. We engineered mice to express different combinations of TFs in Müller glia, including Ascl1, Pou4f2, Islet1, and Atoh1. Using immunohistochemistry, single-cell RNA sequencing, single-cell assay for transposase-accessible chromatin sequencing, and electrophysiology, we find that retinal ganglion–like cells can be regenerated in the damaged adult mouse retina in vivo with targeted overexpression of developmental retinal ganglion cell TFs