Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA251399 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Sox4 links tumor suppression to accelerated aging in mice [Telogen]
| PRJNA251400 | ENA
Project description:Sox4 links tumor suppression to accelerated aging in mice
| PRJNA251398 | ENA
Project description:Sox4 is a transcription factor expressed during embryonic development and some adult tissues such as lymphoid organs, pancreas, intestine and skin. During embryogenesis, Sox4 regulates the survival of mesenchymal and neural progenitors, lymphocyte and myeloid differentiation, and pancreatic, bone and cardiac development. Aberrantly increased Sox4 expression is linked to malignant transformation and metastasis in several types of human cancer. To study the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display a plethora of age-related degenerative disorders and reduced spontaneous cancer incidence, indicating a role for this protein in maintaining adult tissue homeostasis and in tumor growth. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO) in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and DNA damage accumulation, accompanied by resistance to chemical carcinogenesis. These phenotypes correlate with downregulation of cell cycle, DNA repair and skin stem cell genes in the absence of Sox4. Altogether, these findings highlight the importance of Sox4 in adult tissue homeostasis and cancer. Sox4 WT and cKO (conditional KO in skin) were plucked and skin was collected for microarray hibridization, to study the contribution of Sox4 to hair regeneration and hair follicle stem cell activation
2015-05-20 | E-GEOD-58153 | biostudies-arrayexpress
Project description:Mechanisms of Aging in Senescence-Accelerated Mice
| PRJNA97507 | ENA
Project description:Mammalian injury responses are characterized by fibrosis and scarring rather than the functional regeneration observed in other phyla. Limited regenerative capacity in mammals could reflect a loss of pro-regeneration programs or active suppression by genes functioning akin to tumor suppressors. To uncover programs governing regeneration in mammals, we investigated Wound Induced Hair Neogenesis (WIHN), a rare example of regeneration in adult mammals1,2. Through comprehensive screening of transcripts associated with both WIHN and human facial rejuvenation after laser treatment, we found the endoribonuclease RNase L to be a powerful suppressor of regeneration. Rnasel-/- mice exhibit remarkable regenerative capacity and accelerated wound healing following injury through the production of IL-36α. Consistent with the known role of RNase L to stimulate caspase-1 signaling, we find that pharmacologic inhibition of caspases promotes regeneration in an IL-36-dependent manner. These responses are not limited to skin but occur following intestinal injury as well, suggesting that suppression of regeneration is a general characteristic of mammalian wound healing. Taken together, this work suggests a therapeutic strategy to uncover latent regenerative capacity and promote functional response to injury. Biopsies of re-epithelialized tissue were recovered from wild-type or Rnasel KO mice approximately 10 days after wounding. Total RNA was extracted and sent for microarray analysis.
2021-11-18 | GSE164003 | GEO
Project description:Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). We used ChIP-seq to unfold genome-wide chromatin landscapes of Nfatc1 and dissect the biological relevence of its upstream BMP signaling in HFSC aging. Telogen quiescent hair follicle stem cells (HFSCs) were FACS-purified for ChIP-sequcencing.
2013-11-14 | E-GEOD-52328 | biostudies-arrayexpress
Project description:Transcriptome sequencing data from the hair regeneration in obob knockout, aging, chemotherapy and young mice.
| PRJNA910674 | ENA
Project description:Cell fates are defined by specific transcriptional program. Previously, we developed a unique stem cell regeneration mouse model, in which transcriptional program for ectoderm organs such as tooth and skin is switched. Genomic deletion of one subunit of Mediator complex, Med1, resulted in defective enamel regeneration, in which dental stem cells were inhibited from undergoing transcriptional program for dental fate. In stead, they exerted skin program for both hair and epidermis, and post-natally regenerate ectopic hairs in the incisors. Here, we report that Med1 also modulates epidermal and hair cell fates in the skin. Med1 ablation further enhanced epidermal and sebocyte fates, and accelerated injury induced epidermal regeneration. However, it blunted hair fate resulting in hair loss in the skin. Ablation of Med1 increased the number of isthmus stem cells and epidermal stem cells, which regenerate epidermis during cutaneous wound healing process. Med1 deficiency also constitutively activated these stem cells and increased their proliferation. Microarray profiling indicated that Med1 deletion causes activation of β-catenin and suppression of TGFβ signaling. Med1 deficiency induced the expression of β-catenin target genes to control cell fate and proliferation. It also decreased TGFβ expression in interfollicular epidermis. Med1 deficiency increased the proliferation and migration of epidermal cells, and induced nuclear translocation of β-catenin, and decreased TGFβ1 expression in vitro. Our finding together with previous observations demonstrated that Med1 governs ectoderm cell fate in both tooth and skin. Med1 ablation blunts hair fate but induces epidermal and sebocyte cell fates to accelerated injury induced epidermal regeneration in the skin. Accelerated regeneration is derived from constitutive activation of epidermal stem cells accompanied with increased proliferation and migration of their progeny by balancing of β-catenin induced growth promoting and TGFβ mediated growth inhibitory activities in the skin.
2017-06-30 | GSE89967 | GEO
Project description:DNA damage represents one of the cell intrinsic causes of stem cell aging, which leads to differentiation induced removal of damaged stem cells in skin and blood. Dietary restriction (DR) retards aging across various species including several strains of laboratory mice. Whether, DR has the potential to ameliorate DNA damage driven stem cell exhaustion remains incompletely understood. Here, we show that DR strongly extends the time to hair graying in response to γ–irradiation (IR) induced DNA damage of C57BL/6J mice. The study shows that DR prolongs quiescence of hair follicle stem cells (HFSCs) by silencing gene regulatory networks and metabolic switches that control proliferation and tissue regeneration. DR-mediated prolongation of HSFC quiescence blocks hair growth and prevents the depletion of HFSCs and ckit+ melanoblasts in response to IR. However, prolongation of HSFCs quiescence also leads to a suppression of DNA repair pathways and cannot prevent melanoblast loss and hair graying in the long run, when hair cycling is re- initiated even after extended periods of time. Together, these results support a model indicating that nutrient deprivation can delay but not heal DNA damage driven extinction of HFSCs and melanoblasts by stalling HSFCs in a prolonged state of quiescence coupled with inhibition of DNA repair. Disconnecting these two types of responses to DR could have the potential to delay stem cell aging.
2024-02-21 | GSE156014 | GEO
Project description:Aging organs functionally and structurally decline with the loss of their regenerative capabilities, yet the existence of distinct cell division programs that determine organ fates is unknown. Hair follicles, mammalian mini-organs that grow hair, miniaturize by aging. Here we report that hair follicle regeneration and aging are driven by distinct cell division types of hair follicle stem cells (HFSCs). Cell fate tracing and cell division axis analysis in mice revealed that HFSCs undergo symmetric and asymmetric cell divisions to generate a new bulge, yet preferentially provoke “stress-responsive type” asymmetric cell divisions that generate aberrantly differentiating cells upon age/stress. That dynamic program with repetitive divisions efficiently eradicates those cells through defective association and stabilization of a hemidesmosomal protein COL17A1 and a cell-polarity-protein aPKCλ in HFSCs, thereby causing organ aging. The forced stabilization of COL17A1 rescued organ aging through aPKCλ stabilization. These results demonstrate that distinct cell division programs govern tissue/organ fates.
2020-12-25 | GSE124119 | GEO