Le TGFβ, un trouble-fête dans la niche des cellules souches neurales adultes

Pineda, José Ramón; Boussin, François D.; Mouthon, Marc‐André

doi:10.1051/medsci/2013296006

Cited by 7 publications

(2 citation statements)

References 11 publications

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“…TGF-β1 expression has been reported to rise with age in the subventricular zone of the forebrain [ 34 , 40 , 41 ], contributing to a decline in SVZ neurogenesis. In contrast, GDF11, which like TGF-β1 signals through ALK5/TGFBR2 receptor complex and pSmad2/3, has been suggested to enhance SVZ neurogenesis [ 9 ].…”

Section: Resultsmentioning

confidence: 99%

Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal

et al. 2015

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Stem cell function declines with age largely due to the biochemical imbalances in their tissue niches, and this work demonstrates that aging imposes an elevation in transforming growth factor β (TGF-β) signaling in the neurogenic niche of the hippocampus, analogous to the previously demonstrated changes in the myogenic niche of skeletal muscle with age. Exploring the hypothesis that youthful calibration of key signaling pathways may enhance regeneration of multiple old tissues, we found that systemically attenuating TGF-β signaling with a single drug simultaneously enhanced neurogenesis and muscle regeneration in the same old mice, findings further substantiated via genetic perturbations. At the levels of cellular mechanism, our results establish that the age-specific increase in TGF-β1 in the stem cell niches of aged hippocampus involves microglia and that such an increase is pro-inflammatory both in brain and muscle, as assayed by the elevated expression of β2 microglobulin (B2M), a component of MHC class I molecules. These findings suggest that at high levels typical of aged tissues, TGF-β1 promotes inflammation instead of its canonical role in attenuating immune responses. In agreement with this conclusion, inhibition of TGF-β1 signaling normalized B2M to young levels in both studied tissues.

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Section: Resultsmentioning

confidence: 99%

Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal

et al. 2015

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“…Transcriptomic studies revealed that age-related SVZ neurogenesis decline is associated with TGFß signaling and specific cell cycle regulation changes in s-aNSC. A progressive lengthening of aNSC G1 phase with age leads to a decrease in the production of s-TAP, s-iNB and s-mNB [20][21][22] . However, despite the decrease of neurogenesis with aging the s-iNB remained more abundant than s-aNSC and s-TAP in the aged brain 21 .…”

mentioning

confidence: 99%

Switching of RNA splicing regulators in immature neuroblasts: a key step in adult neurogenesis

Bernou

Mouthon

Daynac

et al. 2023

Preprint

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The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB or D cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into 2 subtypes, D1 and D2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.

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Reconstituting neurovascular unit based on the close relations between neural stem cells and endothelial cells: an effective method to explore neurogenesis and angiogenesis

Wang

Chen

Jiang

et al. 2019

Reviews in the Neurosciences

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The discovery of neural stem cells (NSCs) and their microenvironment, the NSC niche, brought new therapeutic strategies through neurogenesis and angiogenesis for stroke and most neurodegenerative diseases, including Alzheimer’s disease. Based on the close links between NSCs and endothelial cells, the integration of neurogenesis and angiogenesis of the NSC niche is also a promising area to the neurovascular unit (NVU) modeling and is now offering a powerful tool to advance our understanding of the brain. In this review, critical aspects of the NVU and model systems are discussed. First, we briefly describe the interaction of each part in the NSC niche. Second, we introduce the co-culture system, microfluidic platforms, and stem cell-derived 3D reconstitution used in NVU modeling based on the close relations between NSCs and endothelial cells, and various characteristics of cell interactions in these systems are also described. Finally, we address the challenges in modeling the NVU that can potentially be overcome by employing strategies for advanced biomaterials and stem cell co-culture use. Based on these approaches, researchers will continue to develop predictable technologies to control the fate of stem cells, achieve accurate screening of drugs for the nervous system, and advance the clinical application of NVU models.

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Le TGFβ, un trouble-fête dans la niche des cellules souches neurales adultes

Cited by 7 publications

References 11 publications

Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal

Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal

Switching of RNA splicing regulators in immature neuroblasts: a key step in adult neurogenesis

Reconstituting neurovascular unit based on the close relations between neural stem cells and endothelial cells: an effective method to explore neurogenesis and angiogenesis

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