Loss of SATB1 induces p21-dependent cellular senescence in post-mitotic dopaminergic neurons Journal Article
| Authors: | Riessland, M.; Kolisnyk, B.; Kim, T. W.; Cheng, J.; Ni, J.; Pearson, J. A.; Park, E. J.; Dam, K.; Acehan, D.; Ramos-Espiritu, L. S.; Wang, W.; Zhang, J.; Shim, J. W.; Ciceri, G.; Brichta, L.; Studer, L.; Greengard, P. |
| Article Title: | Loss of SATB1 induces p21-dependent cellular senescence in post-mitotic dopaminergic neurons |
| Abstract: | 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 that 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 in the pathology of Parkinson's disease. © 2019 Elsevier Inc. SATB1 is a genetic risk factor for Parkinson's disease. Riessland et al. show that loss of SATB1 induces cellular senescence in mouse and human dopaminergic but not cortical neurons and that these senescent neurons secrete inflammatory factors that induce an immune response in mice. © 2019 Elsevier Inc. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; comparative study; cell proliferation; mitosis; animal cell; mouse; animal tissue; embryo; protein protein interaction; animal experiment; transcription factor; in vivo study; neural stem cell; in vitro study; transcriptomics; gene expression regulation; gene repression; reactive oxygen metabolite; stem cells; binding protein; cell count; cyclin dependent kinase inhibitor 1a; parkinson disease; protein p21; nerve cell differentiation; cytoskeleton; transcriptome; cell aging; dopamine; dopaminergic nerve cell; neuropathology; p21; regulator protein; neurodegeneration; cellular senescence; parkinson's disease; substantia nigra; guide rna; cell respiration; neuroinflammation; human; male; female; priority journal; article; gene knockout; satb1; senolytics; special at rich sequence binding protein 1 |
| Journal Title: | Cell Stem Cell |
| Volume: | 25 |
| Issue: | 4 |
| ISSN: | 1934-5909 |
| Publisher: | Cell Press |
| Date Published: | 2019-10-03 |
| Start Page: | 514 |
| End Page: | 530.e8 |
| Language: | English |
| DOI: | 10.1016/j.stem.2019.08.013 |
| PUBMED: | 31543366 |
| PROVIDER: | scopus |
| PMCID: | PMC7493192 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2019 -- Source: Scopus |
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