SoxD genes are required for adult neural stem cell activation

Medina-Menendez, Cristina; García-Corzo, Laura; Córdoba-Beldad, Carmen M; Quiroga, Alejandra C.; Barca, Elena Calleja; Zinchuk, Valeriya; Muñoz-López, Sara; Rodríguez‐Martín, Pilar; Ciorraga, Maria; Colmena, Inés; Fernández, Silvia; Vicario‐Abejón, Carlos; Nicolis, Silvia K.; Lefebvre, Véronique; Mira, Helena; Morales, Aixa V.

doi:10.1016/j.celrep.2022.110313

Cited by 24 publications

(22 citation statements)

References 50 publications

(73 reference statements)

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“…Among the regions with increased distal accessibility in HepLPC-P3, SOX6 and SOX21 were enriched. SOX6 and SOX21 are highly expressed in stem/progenitor cells and are required for stem cell activation and maintenance [ 31 , 32 ]. Two embryonic-developmental genes, GRHL2 and PRDM10 , were found to be enriched.…”

Section: Resultsmentioning

confidence: 99%

Integration of ATAC-Seq and RNA-Seq reveals FOSL2 drives human liver progenitor-like cell aging by regulating inflammatory factors

et al. 2023

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Background Human primary hepatocytes (PHCs) are considered to be the best cell source for cell-based therapies for the treatment of end-stage liver disease and acute liver failure. To obtain sufficient and high-quality functional human hepatocytes, we have established a strategy to dedifferentiate human PHCs into expandable hepatocyte-derived liver progenitor-like cells (HepLPCs) through in vitro chemical reprogramming. However, the reduced proliferative capacity of HepLPCs after long-term culture still limits their utility. Therefore, in this study, we attempted to explore the potential mechanism related to the proliferative ability of HepLPCs in vitro culture. Results In this study, analysis of assay for transposase accessible chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) were performed for PHCs, proliferative HepLPCs (pro-HepLPCs) and late-passage HepLPCs (lp-HepLPCs). Genome-wide transcriptional and chromatin accessibility changes during the conversion and long-term culture of HepLPCs were studied. We found that lp-HepLPCs exhibited an aged phenotype characterized by the activation of inflammatory factors. Epigenetic changes were found to be consistent with our gene expression findings, with promoter and distal regions of many inflammatory-related genes showing increased accessibility in the lp-HepLPCs. FOSL2, a member of the AP-1 family, was found to be highly enriched in the distal regions with increased accessibility in lp-HepLPCs. Its depletion attenuated the expression of aging- and senescence-associated secretory phenotype (SASP)-related genes and resulted in a partial improvement of the aging phenotype in lp-HepLPCs. Conclusions FOSL2 may drive the aging of HepLPCs by regulating inflammatory factors and its depletion may attenuate this phenotypic shift. This study provides a novel and promising approach for the long-term in vitro culture of HepLPCs.

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Section: Resultsmentioning

confidence: 99%

Integration of ATAC-Seq and RNA-Seq reveals FOSL2 drives human liver progenitor-like cell aging by regulating inflammatory factors

et al. 2023

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“…Numerous studies showed that the self-renewal and/or differentiation capacities of NSCs and NPCs in neurogenic regions of the adult brain are regulated by several SOX genes: SOX2, SOX21, SOX9, SOX4 and SOX11 [63][64][65]88,109,110]. Furthermore, a recent study in the hippocampus showed the critical role of SOX5 and SOX6 in the transition of NSCs from quiescence to activation [89].…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

“…qNSCs-quiescent neural stem cells, NPCs-neural progenitor cells, DG-dentate gyrus, CA1-cornu ammonis 1, CA3cornu ammonis 3. The scheme is based on the previously reported publications [16,19,22,23,89].…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

The Role of SOX Transcription Factors in Ageing and Age-Related Diseases

Stevanović

Lazic

Schwirtlich

et al. 2023

IJMS

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The quest for eternal youth and immortality is as old as humankind. Ageing is an inevitable physiological process accompanied by many functional declines that are driving factors for age-related diseases. Stem cell exhaustion is one of the major hallmarks of ageing. The SOX transcription factors play well-known roles in self-renewal and differentiation of both embryonic and adult stem cells. As a consequence of ageing, the repertoire of adult stem cells present in various organs steadily declines, and their dysfunction/death could lead to reduced regenerative potential and development of age-related diseases. Thus, restoring the function of aged stem cells, inducing their regenerative potential, and slowing down the ageing process are critical for improving the health span and, consequently, the lifespan of humans. Reprograming factors, including SOX family members, emerge as crucial players in rejuvenation. This review focuses on the roles of SOX transcription factors in stem cell exhaustion and age-related diseases, including neurodegenerative diseases, visual deterioration, chronic obstructive pulmonary disease, osteoporosis, and age-related cancers. A better understanding of the molecular mechanisms of ageing and the roles of SOX transcription factors in this process could open new avenues for developing novel strategies that will delay ageing and prevent age-related diseases.

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“…More specifically, PNS enhanced the expression of bromodomain containing genes Atad2 (ATPase family AAA domain containing 2) and Brd8 (bromodomain containing 8) that have been shown to be involved in ESR1 (estrogen receptor alpha) mediated transcriptional regulation of cell proliferation in cancer cell lines [58][59][60] . PNS increased expression levels of Wnt pathway modulators Ezh2, Tcf4, Ephb2, and Sox2, which play important roles in sustaining cell stemness and promoting cell proliferations [61][62][63][64][65] . The Wnt and the estrogen signaling pathways are tightly associated with MAPK3/1 signaling to stimulate tumorigensis 26,66,67 .…”

Section: Fig5c)mentioning

confidence: 99%

Transcriptomic analyses reveal prenatal stress promotes late-onset neural stem cell proliferation in adult male offspring

Wang

Zhou

Lee

et al. 2022

Preprint

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Perturbations during critical time windows in the normal series of development can lead to adverse functional consequences that manifest later in life. Here, we report that prenatal stress (PNS) during the last week of gestation (E14-delivery) dramatically increased the number of proliferating neural stem/progenitor cells (NSC/NPCs) in the ependymal-subventricular zone (E-SVZ) of male mouse offspring. PNS did not cause significant cell death or a deficit in neuroblast migration to the olfactory bulb (OB). Olfactory behavioral tests showed that while prenatally stressed male mice displayed normal olfactory function in differentiating nonsocial odors, these mice showed impairment in discriminating different social smells. Bulk and single nucleus transcriptomic analyses combined with rescue assays using mitogen-activated protein kinases (MAPK) phosphorylation inhibitors revealed that PNS exposure during the critical period of neurogenesis promoted NSC/NPC proliferation in adult male offspring by sustaining MAPK3/1 activity. Compared to prenatally stressed males, their female littermates showed less change in the number of proliferating cells in the E-SVZ.

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SoxD genes are required for adult neural stem cell activation

Cited by 24 publications

References 50 publications

Integration of ATAC-Seq and RNA-Seq reveals FOSL2 drives human liver progenitor-like cell aging by regulating inflammatory factors

Integration of ATAC-Seq and RNA-Seq reveals FOSL2 drives human liver progenitor-like cell aging by regulating inflammatory factors

The Role of SOX Transcription Factors in Ageing and Age-Related Diseases

Transcriptomic analyses reveal prenatal stress promotes late-onset neural stem cell proliferation in adult male offspring

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