Adult Neural Stem Cells Are Alerted by Systemic Inflammation through TNF-α Receptor Signaling

Belenguer, Germán; Duart-Abadía, Pere; Jordán-Pla, Antonio; Domingo-Muelas, Ana; Blasco-Chamarro, Laura; Ferrón, Sacri R.; Morante‐Redolat, José Manuel; Fariñas, Isabel

doi:10.1016/j.stem.2020.10.016

Cited by 94 publications

(100 citation statements)

References 66 publications

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“…Data relative to 10X-Chromium dataset were shown in Figures 2A-D, whereas data relative to the dataset of Telley et al (2019) were shown in Figures 3A-C. We also analyzed bulk-RNAseq data derived from purified NS/PCs from adult murine SVZ (Belenguer et al, 2021). The normalized expression matrix of the dataset of Belenguer et al (2021) was downloaded from GEO database using GSE138243 accession number.…”

Section: Analysis Of Patz1 Transcript Distribution From Publicly Avaimentioning

confidence: 99%

“…We also analyzed bulk-RNAseq data derived from purified NS/PCs from adult murine SVZ (Belenguer et al, 2021). The normalized expression matrix of the dataset of Belenguer et al (2021) was downloaded from GEO database using GSE138243 accession number. Expression data relative to Patz1, Cd9, Slc1a3, Tbr2, Dcxa, and Cd24a genes were reported in the heatmap (scaled data) and in the floating box plot (normalized expression) in Figures 2E,F.…”

Section: Analysis Of Patz1 Transcript Distribution From Publicly Avaimentioning

confidence: 99%

“…Tail pieces from both embryos and adult mice were lysed in tail digestion buffer (50 mM Tris, pH 8.0; 100 mM EDTA, pH 8.0; 100 mM NaCl; 1% SDS) plus proteinase K (0.6 mg/ml) over-night at 55 • C. Genomic DNA was extracted by Belenguer et al (2021) phenol/chloroform/isoamyl alcohol (1:1), precipitated with 95% ethanol and dissolved in TE (Tris/EDTA) buffer, pH 7.5. A set of three primers was used to detect both normal and mutant Patz1 alleles by polymerase chain reactions (PCR), as previously described (Monaco et al, 2018).…”

Section: Patz1 Genotype Analysismentioning

confidence: 99%

“…By analyzing the 10× Genomics 10K E18 Brain cells dataset, we found an enrichment of Patz1 expression in early apical radial glia/neural stem cells (RG/NSCs) and intermediate progenitors (IPCs) (Figures 2A-D). We also examined Patz1 expression in a dataset of bulk RNA sequencing from sorted types of progenitors from mouse adult SVZ (Belenguer et al, 2021), finding that Patz1 was expressed in the entire proliferating lineage with an enrichment in neural progenitor cells (NPCs) and neuroblasts (NBs) (Figures 2E,F). A further analysis, on single-cell RNA sequencing of sorted progenitor cells belonging to presumptive somato-sensory cortex of E12, E13, E14, and E15 mouse embryos (Telley et al, 2019), confirmed an enrichment of Patz1 expression during development in early apical radial glia/neural stem cells (RG/NSCs), mainly at the E12 stage (Figures 3A-C).…”

Section: Patz1 Is Enriched In Proliferating Neural Progenitor Cells Imentioning

confidence: 99%

“…In the adult, neural stem/progenitor cells (NS/PCs) are also present in the SVZ. NSCs activate, upon an injury or inflammatory stimulus, to produce transient-amplifying neural progenitor cells (NPCs) that divide and generate a different type of proliferating progenitors, the neuroblasts (NBs), that eventually differentiate to produce newborn neurons (Alvarez-Buylla and Garcia-Verdugo, 2002;Chaker et al, 2016;Belenguer et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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

Mancinelli

Vitiello

Donnini

et al. 2021

Front. Cell Dev. Biol.

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Proper regulation of neurogenesis, the process by which new neurons are generated from neural stem and progenitor cells (NS/PCs), is essential for embryonic brain development and adult brain function. The transcription regulator Patz1 is ubiquitously expressed in early mouse embryos and has a key role in embryonic stem cell maintenance. At later stages, the detection of Patz1 expression mainly in the developing brain suggests a specific involvement of Patz1 in neurogenesis. To address this point, we first got insights in Patz1 expression profile in different brain territories at both embryonic and postnatal stages, evidencing a general decreasing trend with respect to time. Then, we performed in vivo and ex vivo analysis of Patz1-knockout mice, focusing on the ventricular and subventricular zone, where we confirmed Patz1 enrichment through the analysis of public RNA-seq datasets. Both embryos and adults showed a significant reduction in the number of Patz1-null NS/PCs, as well as of their self-renewal capability, compared to controls. Consistently, molecular analysis revealed the downregulation of stemness markers in NS/PCs derived from Patz1-null mice. Overall, these data demonstrate the requirement of Patz1 for NS/PC maintenance and proliferation, suggesting new roles for this key transcription factor specifically in brain development and plasticity, with possible implications for neurodegenerative disorders and glial brain tumors.

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Section: Analysis Of Patz1 Transcript Distribution From Publicly Avaimentioning

confidence: 99%

Section: Analysis Of Patz1 Transcript Distribution From Publicly Avaimentioning

confidence: 99%

Section: Patz1 Genotype Analysismentioning

confidence: 99%

Section: Patz1 Is Enriched In Proliferating Neural Progenitor Cells Imentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Mancinelli

Vitiello

Donnini

et al. 2021

Front. Cell Dev. Biol.

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TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP

Su,

Li,

Lin

et al. 2023

Advanced Science

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Regular quiescence and activation are important for the function of bone marrow mesenchymal stem cells (BMMSC), multipotent stem cells that are widely used in the clinic due to their capabilities in tissue repair and inflammatory disease treatment. TNF‐α is previously reported to regulate BMMSC functions, including multilineage differentiation and immunoregulation. The present study demonstrates that TNF‐α impedes quiescence and promotes the activation of BMMSC in vitro and in vivo. Mechanistically, the TNF‐α‐induced expression of KAT2A promotes the succinylation of VCP at K658, which inhibits the interaction between VCP and MFN1 and thus inhibits mitophagy. Furthermore, activated BMMSC exhibits stronger fracture repair and immunoregulation functions in vivo. This study contributes to a better understanding of the mechanisms of BMMSC quiescence and activation and to improving the effectiveness of BMMSC in clinical applications.

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Post natal expression of Prx1 labels appendicular restricted progenitor cell populations of multiple tissues

Bragdon

Bennie

Molinelli

et al. 2022

Journal Cellular Physiology

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Currently, there is no consensus whether there is a single or multiple postnatal stem cell population(s) that contribute to skeletal homeostasis and postnatal bone formation. A known population of cells that express Prx1 contributes to postnatal bone formation. Prx1 expression also connotes calvaria and appendicular tissues during embryonic development. A transgenic tamoxifen inducible Prx1 reporter mouse was used for lineage tracking, to characterize the postnatal contribution of Prx1 expressing cells in skeletal homeostasis and bone formation. Under homeostatic conditions Prx1 labeling gave rise to a transient yet rapid turnover cell population at the periosteal and endosteal surfaces, along muscle fibers, and within the medial layers of vessels both within the muscle and marrow compartments of the appendicular skeleton. Fracture and ectopic bone formation of both fore and hind limbs showed recruitment and expansion of Prx1‐derived cells in newly formed bone tissues. Prx1 labeled cells were limited or absent at axial skeletal sites during both homeostasis and after induction of bone formation. Last, Prx1‐derived cells differentiated into multiple cell lineages including vascular smooth muscle, adipose, cartilage, and bone cells. These results show that Prx1 expression retained its embryonic tissue specification and connotes a stem/progenitor cell populations of mesenchymal tissue progenitors.

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Adult Neural Stem Cells Are Alerted by Systemic Inflammation through TNF-α Receptor Signaling

Cited by 94 publications

References 66 publications

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

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

TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP

Post natal expression of Prx1 labels appendicular restricted progenitor cell populations of multiple tissues

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