The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation

Mancinelli, Sara; Vitiello, Marianna; Donnini, Maria; Mantile, Francesca; Palma, Giuseppe; Luciano, Antonio; Arra, Claudio; Cerchia, Laura; Liguori, Giovanna L.

doi:10.3389/fcell.2021.657149

Cited by 9 publications

(7 citation statements)

References 62 publications

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“…It has been suggested that hippocampus damage plays a vital role in the pathophysiology of epilepsy and depression. [ 35 ] In the present study, H&E analysis indicated a neuronal loss in the hippocampal regions (CA1, CA3, and CA1) of PTZ mice. Meanwhile, remarkably increased FJB‐positive cells, which represent neuronal degeneration, were also exhibited in PTZ group, while administration of EPA produced the best effect on the significant reduction of the degeneration of the hippocampus.…”

Section: Discussionsupporting

confidence: 58%

DHA and EPA Prevent Seizure and Depression‐Like Behavior by Inhibiting Ferroptosis and Neuroinflammation via Different Mode‐of‐Actions in a Pentylenetetrazole‐Induced Kindling Model in Mice

Wang

Xiao

Yang

et al. 2022

Molecular Nutrition Food Res

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Scope: It has been reported that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anticonvulsant effects, yet the respective mechanism of EPA and DHA on epilepsy is still unclarified. This study aims to investigate the effect of EPA and DHA on pentylenetetrazol (PTZ) induced seizures and depression. Methods and results: The administration of EPA and DHA at a dose of 1% w/w significantly inhibits PTZ-induced seizures and depressive-like behavior, whereas EPA outcompetes DHA. Further mechanistic studies reveal that the higher effect of EPA can be partly attributed to the promotion of M2 polarization, inhibition of M1 polarization of microglia, and lower iron content in the brain, resulting from the stronger activation of nuclear factor E2-related factor 2 (Nrf2). This study finds that DHA and EPA comparably inhibit NLRP3 inflammasome activation but with different mode-of-actions: EPA prefers to inhibit the binding of NLRP3 and ASC, while DHA decreases the protein levels of ASC and Caspase-1. Conclusions: These results indicate that DHA and EPA can efficaciously alleviate PTZ-induced seizure and depressive-like behavior but with different efficiency and molecular mechanisms.

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Section: Discussionsupporting

confidence: 58%

DHA and EPA Prevent Seizure and Depression‐Like Behavior by Inhibiting Ferroptosis and Neuroinflammation via Different Mode‐of‐Actions in a Pentylenetetrazole‐Induced Kindling Model in Mice

Wang

Xiao

Yang

et al. 2022

Molecular Nutrition Food Res

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“…Next, we sought to identify TFs with differential activity associated with chromatin accessibility by motif footprinting using HINT-ATAC and motif enrichment with GimmeMotifs maelstrom. HINT analysis using the CIS-BP motif database identi ed decreased footprinting activity of TFs controlling neuron differentiation (HEYL, PATZ1) [91,92], mitochondrial energy and neuron function (NRF1, GMEB1) [93], as well as synaptic plasticity (CREM) [94] and increased footprinting activity of early pro-neural TFs (ASCL1, NEUROG2, ARNT2) [95,96] across all three mutations (Fig. 3D-F).…”

Section: Resultsmentioning

confidence: 99%

Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease

Valdes

Caldwell

Liu

et al. 2022

Preprint

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Background Mutations in PSEN1, PSEN2, and APP can lead to Alzheimer’s disease (AD) with an early age at onset (AAO) and hallmark progressive cognitive decline. These mutations are highly penetrant. Although mutations in PSEN1 are more common and usually have an earlier AAO, certain mutations in PSEN1 cause a later AAO, similar to PSEN2 and APP mutations. We sought to determine whether common disease endotypes exist across these mutations with a relatively late AAO. Methods We generated hiPSC-derived neurons from patients harboring autosomal-dominant, familial Alzheimer’s disease (FAD) mutations in PSEN1, PSEN2, and APP with a documented age at onset (AAO) around 55 years: PSEN1A79V, PSEN2N141I, and APPV717I. We carried out RNA-seq and ATAC-seq to mechanistically characterize the gene expression and chromatin accessibility changes, respectively. Differential expression analysis, enrichment analysis, TF activity identification, and co-expression module detection were performed for RNA-seq. Differential peak analysis and annotation, TF motif footprinting and differential motif accessibility, and peak functional enrichment were performed for ATAC-seq. This approach allowed us to identify the correlation between gene expression and chromatin accessibility associated with key disease endotypes. Results Using a multiomics approach, we identify and characterize common endotypes in mutations across all three FAD genes: dedifferentiation of a mature neuron to a less differentiated quasi-neuron state, dysregulation of synaptic signaling, repression of mitochondrial function and metabolism, and inflammation. The integrativeanalysis allowed us to ascertain the master transcriptional regulators associated with these endotypes, including REST, ASCL1, and ZIC family members (activation), as well as NRF1 (repression). Conclusions Our findings characterize the common regulatory changes within endotypes across these FAD mutations. However, the severity of dysregulation often differs between PSEN1, PSEN2, and APP mutations both in magnitude and direction. The overarching common link between mutations in FAD genes is the reversion to a less-differentiated neuron state. The transcriptional regulatory mechanisms described within disease endotypes offer potential targets for therapeutic interventions.

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“…In this context, PATZ1 overexpression in LUSCs appears consonant with the stem cell phenotype of this subtype. In fact, PATZ1 is required for pluripotency maintenance of embryonic stem cells [ 51 ], plays an essential role in the reprogramming of differentiated cells toward stem cells [ 13 ], and governs the self-renewal ability of adult stem cells, including neural and cancer stem cells [ 52 , 53 ]. Strikingly, the expression of PATZ1 and the stem cell marker SOX2 are positively associated in NSCLC tissues ( Figure S8 ).…”

Section: Discussionmentioning

confidence: 99%

PATZ1 in Non-Small Cell Lung Cancer: A New Biomarker That Negatively Correlates with PD-L1 Expression and Suppresses the Malignant Phenotype

Luca

Franco

Napolitano

et al. 2023

Cancers

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Non-small cell lung cancer (NSCLC), the leading cause of cancer death worldwide, is still an unmet medical problem due to the lack of both effective therapies against advanced stages and markers to allow a diagnosis of the disease at early stages before its progression. Immunotherapy targeting the PD-1/PD-L1 checkpoint is promising for many cancers, including NSCLC, but its success depends on the tumor expression of PD-L1. PATZ1 is an emerging cancer-related transcriptional regulator and diagnostic/prognostic biomarker in different malignant tumors, but its role in lung cancer is still obscure. Here we investigated expression and role of PATZ1 in NSCLC, in correlation with NSCLC subtypes and PD-L1 expression. A cohort of 104 NSCLCs, including lung squamous cell carcinomas (LUSCs) and adenocarcinomas (LUADs), was retrospectively analyzed by immunohistochemistry for the expression of PATZ1 and PD-L1. The results were correlated with each other and with the clinical characteristics, showing on the one hand a positive correlation between the high expression of PATZ1 and the LUSC subtype and, on the other hand, a negative correlation between PATZ1 and PD-L1, validated at the mRNA level in independent NSCLC datasets. Consistently, two NSCLC cell lines transfected with a PATZ1-overexpressing plasmid showed PD-L1 downregulation, suggesting a role for PATZ1 in the negative regulation of PD-L1. We also showed that PATZ1 overexpression inhibits NSCLC cell proliferation, migration, and invasion, and that Patz1-knockout mice develop LUAD. Overall, this suggests that PATZ1 may act as a tumor suppressor in NSCLC.

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The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation

Cited by 9 publications

References 62 publications

DHA and EPA Prevent Seizure and Depression‐Like Behavior by Inhibiting Ferroptosis and Neuroinflammation via Different Mode‐of‐Actions in a Pentylenetetrazole‐Induced Kindling Model in Mice

DHA and EPA Prevent Seizure and Depression‐Like Behavior by Inhibiting Ferroptosis and Neuroinflammation via Different Mode‐of‐Actions in a Pentylenetetrazole‐Induced Kindling Model in Mice

Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease

PATZ1 in Non-Small Cell Lung Cancer: A New Biomarker That Negatively Correlates with PD-L1 Expression and Suppresses the Malignant Phenotype

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