RT Journal Article
SR Electronic
T1 Loss of SATB1 Induces a p21 Dependent Cellular Senescence Phenotype in Dopaminergic Neurons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 452243
DO 10.1101/452243
A1 Markus Riessland
A1 Benjamin Kolisnyk
A1 Tae Wan Kim
A1 Jia Cheng
A1 Jason Ni
A1 Jordan A. Pearson
A1 Emily J. Park
A1 Kevin Dam
A1 Devrim Acehan
A1 Lavoisier S. Ramos-Espiritu
A1 Wei Wang
A1 Jack Zhang
A1 Jae-won Shim
A1 Gabriele Ciceri
A1 Lars Brichta
A1 Lorenz Studer
A1 Paul Greengard
YR 2018
UL http://biorxiv.org/content/early/2018/10/24/452243.abstract
AB Cellular senescence is a mechanism used by mitotic cells to prevent uncontrolled cell division. As senescent cells persist in tissues, they cause local inflammation and are harmful to surrounding cells, contributing to aging. Generally, neurodegenerative diseases, such as Parkinson‘s, are disorders of aging. The contribution of cellular senescence to neurodegeneration is still unclear. SATB1 is a DNA binding protein associated with Parkinson’s disease. We report that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons. Loss of SATB1 causes activation of a cellular senescence transcriptional program in dopamine neurons, both in human stem cell-derived dopaminergic neurons and in mice. We observed phenotypes which are central to cellular senescence in SATB1 knockout dopamine neurons in vitro and in vivo. Moreover, we found that SATB1 directly represses expression of the pro-senescence factor, p21, in dopaminergic neurons. Our data implicate senescence of dopamine neurons as a contributing factor to the pathology of Parkinson’s disease.