Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina

Thanh Hoang; Dong Won Kim; Haley Appel; Nicole A. Pannullo; Patrick Leavey; Manabu Ozawa; Sika Zheng; Minzhong Yu; Neal S. Peachey; Seth Blackshaw

Cell Reports (Jun 2022)

Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina

Thanh Hoang,
Dong Won Kim,
Haley Appel,
Nicole A. Pannullo,
Patrick Leavey,
Manabu Ozawa,
Sika Zheng,
Minzhong Yu,
Neal S. Peachey,
Seth Blackshaw

Affiliations

Thanh Hoang: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding author
Dong Won Kim: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding author
Haley Appel: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Nicole A. Pannullo: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Patrick Leavey: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Manabu Ozawa: Center for Experimental Medicine and Systems Biology, University of Tokyo, Tokyo, Japan
Sika Zheng: Division of Biomedical Sciences, University of California, Riverside, CA, USA
Minzhong Yu: Department of Ophthalmic Research, Cole Eye Institute, Cleveland, OH, USA; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
Neal S. Peachey: Department of Ophthalmic Research, Cole Eye Institute, Cleveland, OH, USA; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
Seth Blackshaw: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding author

Journal volume & issue: Vol. 39, no. 11
p. 110849

Abstract

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Summary: Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Mϋller glia into functional neurons. Here, we use a combination of genetic lineage tracing, single-cell RNA sequencing (scRNA-seq), and electroretinogram analysis to show that selective induction of either heterozygous or homozygous loss-of-function mutants of Ptbp1 in adult retinal Mϋller glia does not lead to any detectable level of neuronal conversion. Only a few changes in gene expression are observed in Mϋller glia following Ptbp1 deletion, and glial identity is maintained. These findings highlight the importance of using genetic manipulation and lineage-tracing methods in studying cell-type conversion.

CP: Cell biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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