Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons

Abstract

Highlights d FACS of NURR1::GFP dopaminergic (DA) precursors enriches DA neuron culture purity d SATB1 KO DA neurons show hallmarks of cellular senescence, including SASP d SATB1 is required to repress CDKN1A in DA neurons d Senescence induced by SATB1 reduction in vivo induces microglial activation

Mechanical stimulation induced osteogenic differentiation of BMSCs through TWIST/E2A/p21 axis

“…In addition, the osteogenesis process simultaneously negatively regulated via the TWIST/E2A/p21 axis. Studies have shown that p21 protein participates in many cell responses, inhibits cell proliferation, promotes cell differentiation and accelerates cell aging [30][31][32]. In addition, p21 also plays an essential role in the biological behavior of BMSCs [33][34][35].…”

Perturbed DNA methylation by sustained overexpression of Gadd45b induces chromatin disorganization, DNA strand breaks and dopaminergic neuron death in mice

“…Among the list of genes underlying a direct or indirect regulation through methylation changes triggered by Gadd45b overexpression, the decrease in expression did not correlate with a specific direction of methylation changes towards hypo- or hypermethylated CpGs but rather with a change in the methylation state throughout the gene body. Satb1 has been described as a dopaminergic-specific regulator of senescence 83 , a dopaminergic neuron cell survival factor 84 and a regulator of global chromatin structuration 85, 86 . The decline in Satb1 expression at 90d p.i.…”

“…After 30 minutes at RT in 100 μM glycine buffer (for TH/mCherry and TH/ORF1p) or 30 minutes at 100°C in demasking citrate buffer (10 mM, pH 6, 0.05% Tween) (for TH/MeCP2, H3K9 or γ-H2AX), sections were first blocked in 10% Fetal Bovine Serum (FBS, Gibco) in the presence of 0.5% Triton X-100 for 1 hour at RT and incubated with primary antibodies overnight at 4°C, washed and further incubated with secondary antibodies for 1 hour at RT. The following primary antibodies used: anti-γ-H2AX (mouse, 1/200, Millipore, clone JBW301), anti-TH (chicken, 1/500, Abcam, ab76442), anti-ORF1p (guinea pig, 1/200, in-house, clone 09 as in 83 , anti-mCherry (mouse, 1/200, Clontech 632543), rabbit anti-H3K9me3 (rabbit, 1/200, Abcam, ab8898) and anti-MeCP2 (rabbit, 1/200, Millipore MABE328). Sections were incubated with appropriate secondary antibodies (488 anti-chicken, 546 anti-mouse, 647 anti-guinea pig, 647 anti-rabbit, 647 anti-mouse, Alexa Fluor, Life Technologies)…”

“…The regional analysis classified DMCs and DMRs in four groups, namely, exons, introns, promoters and intergenic regions.and further incubated with secondary antibodies for 1 hour at RT. The following primary antibodies used: anti--H2AX (mouse, 1/200, Millipore, clone JBW301), anti-TH (chicken, 1/500, Abcam, ab76442), anti-ORF1p (guinea pig, 1/200, in-house, clone 09 as in83 , anti-mCherry (mouse, 1/200, Clontech 632543), rabbit anti-H3K9me3 (rabbit,…”

Nano-Based Theranostic Tools for the Detection and Elimination of Senescent Cells

“…These include nanotechnology-based approaches for detection, site-specific delivery of senolytics and/or senoprobes, and successful elimination of SCs [ 83 , 107 , 108 , 109 , 110 ]. As cellular senescence may be implicated in the pathogenesis of age-related neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [ 111 , 112 ], the use of nano-senolytics in the central nervous system (CNS) seems promising. One should remember that nano-based systems are able to overcome the blood–brain barrier and improve the delivery of encapsulated therapeutic agents and dietary polyphenols at lower systemic doses [ 68 , 74 ].…”