Role of Atg16L1 in skin biology
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE218854 | GEO | 2023/07/13
REPOSITORIES: GEO
Similar Datasets
Project description:Comparative analysis of gene expression in cultured primary keratinocytes isolated from newborn control (K14-cre; GPx4fl/+) and knockout (K14-cre; GPx4fl/fl) mice. Selenoproteins are essential for skin function, as targeted abolition of selenoproteins in epidermal tissue results in newborn mice manifesting gross abnormalities of skin and hair, accompanied by retarded growth and premature death. To investigate whether lack of a single selenoprotein could induce similar phenotypic effect in mice, we generated keratinocyte-specific knockout mice lacking glutathione peroxidase 4 (GPx4), an essential selenoprotein in skin, to examine phenotypic changes resulting from the lack of GPx4 in skin. Ablation of GPx4 results in focal alopecia and disturbed hair follicle morphogenesis, with GPx4 being essential during early stages of hair follicle morphogenesis as well as for keratinocyte adhesion and proliferation in culture. We have generated mice with selective removal of the GPx4 gene in keratinocytes under the control of Keratin-14-cre (K14-cre) promoter. Comparative microarray analysis was performed on RNA samples taken from pooled primary keratinocytes from knockout and control mice from the same litter. Array replicates were performed using RNA samples from three different litters.
2012-12-06 | E-GEOD-34215 | biostudies-arrayexpress
Project description:Comparative analysis of gene expression in cultured primary keratinocytes isolated from newborn control (K14-cre; GPx4fl/+) and knockout (K14-cre; GPx4fl/fl) mice. Selenoproteins are essential for skin function, as targeted abolition of selenoproteins in epidermal tissue results in newborn mice manifesting gross abnormalities of skin and hair, accompanied by retarded growth and premature death. To investigate whether lack of a single selenoprotein could induce similar phenotypic effect in mice, we generated keratinocyte-specific knockout mice lacking glutathione peroxidase 4 (GPx4), an essential selenoprotein in skin, to examine phenotypic changes resulting from the lack of GPx4 in skin. Ablation of GPx4 results in focal alopecia and disturbed hair follicle morphogenesis, with GPx4 being essential during early stages of hair follicle morphogenesis as well as for keratinocyte adhesion and proliferation in culture.
2012-12-06 | GSE34215 | GEO
Project description:In order to unravel the functional role of the linear deubiquitinase OTULIN, we performed single-cell RNA-sequencing on total skin of mice lacking OTULIN selectively in keratinocytes. Keratinocyte-specific OTULIN knock-out (KO) mice develop delineated inflammatory lesion. Through single-cell analysis on lesional and non-lesional skin of mice lacking OTULIN in keratinocytes, we could identify signalling pathways through which these inflammatory lesions appear, allowing us to get new insights on the molecular events that regulate skin homeostasis and mediate skin inflammation.
2021-08-03 | GSE162394 | GEO
Project description:It has long been known that excessive mitotic activity due to H-Ras can block keratinocyte differentiation and cause skin cancer. It is not clear, however, whether there are any innate surveillants that ensure keratinocytes undergoing terminal differentiation, preventing the disease. IKKα induces keratinocyte terminal differentiation and its reduction promotes skin tumor development. However, its nature function in skin cancer is unknown. Here we found that mice with IKKα deletion in keratinocytes or in hair follicle keratinocytes developed a thickened epidermis and spontaneous squamous cell-like carcinomas. Inactivation of epidermal growth factor receptor (EGFR) or reintroduction of IKKα inhibited excessive mitosis, induced terminal differentiation, and prevented skin cancer through an EGFR-driven autocrine loop in mice. Thus, IKKα serves as an innate surveillant. Experiment Overall Design: The differences in gene expression profiles of CHUK deleted mouse keratinocytes compared to wild type mouse keratinocytes were analyzed using two dual-channel agilent microarrays in duplicates.
2009-08-12 | E-GEOD-12111 | biostudies-arrayexpress
Project description:The aim of this study is to survey global gene expression of total thymocytes from wild-type mice and Atg16l1 mutant (hypomorph) mice.
2008-09-10 | GSE12707 | GEO
Project description:It has long been known that excessive mitotic activity due to H-Ras can block keratinocyte differentiation and cause skin cancer. It is not clear, however, whether there are any innate surveillants that ensure keratinocytes undergoing terminal differentiation, preventing the disease. IKKα induces keratinocyte terminal differentiation and its reduction promotes skin tumor development. However, its nature function in skin cancer is unknown. Here we found that mice with IKKα deletion in keratinocytes or in hair follicle keratinocytes developed a thickened epidermis and spontaneous squamous cell-like carcinomas. Inactivation of epidermal growth factor receptor (EGFR) or reintroduction of IKKα inhibited excessive mitosis, induced terminal differentiation, and prevented skin cancer through an EGFR-driven autocrine loop in mice. Thus, IKKα serves as an innate surveillant.
2009-07-14 | GSE12111 | GEO
Project description:The vitamin D receptor (VDR) regulates cell proliferation and differentiation including epidermal keratinocytes by modulating transcription of its target genes. We are investigating the role of VDR in epidermal stem cells and their progenies in the regeneration process of epidermis and hair in the skin. VDR null mice are utilized in which VDR is specifically deleted in keratin 14 (K14) expressing keratinocytes by Cre-lox strategy. The impact of VDR deletion was evaluated by comparison of VDR null mice with no cre littermate control mice. The VDR was abundantly expressed in potential epidermal stem cells including basal cells in interfollicular epidermis (IFE), and in CD34 expressing bulge keratinocytes in hair follicles. Gene expression profiles and subsequent pathway analysis of stem cell enriched keratinocyte populations revealed that the VDR deletion significantly suppressed β-catenin signaling as well as VDR signaling. The role of VDR in epidermal stem cells was studied during hair follicle cycling and wound healing processes. The epidermal stem cells were not appropriately stimulated by hair depilation, and did not reinitiate anagen in the hair follicles resulting in a failure of hair regrowth. In addition, the stem cells were not fully activated after full thickness wounds were generated in VDR null skin under a low calcium diet to suppress compensation pathways. Cell proliferation was not fully induced in potential stem cells located in both IFE and hair follicles near the wounding edges, and re-epithelialization rate was delayed in VDR null skin. Gene expression profiling of the wounded skin (3 days after injury) indicated that β-catenin signaling was not fully induced in VDR null skin comparable to that observed in β-catenin null mice. The β-catenin target genes including Axin2 and cell cycle regulators involved in epidermal stem cell function were not induced in the edges of the wound of VDR null skin. These results demonstrated that VDR plays an essential role in hair cycling and wound healing processes through regulation of β-catenin signaling in epidermal stem cells and their progenies. n=3 CON and KO (each sample contain RNA extracted from keratinocytes, which is isolated from VDR KO and littermate control skins excised from 3 mice)
2015-07-31 | E-GEOD-68729 | biostudies-arrayexpress
Project description:The aim of this study is to survey global gene expression of total thymocytes from wild-type mice and Atg16l1 mutant (hypomorph) mice. Experiment Overall Design: Total RNA was extracted from total thymocytes from the following samples and analyzed: Experiment Overall Design: Atg16l1 hypomorph: 2 mice (7 weeks), 1 male and 1 female Experiment Overall Design: Control: 2 mice (7 weeks), 1 male and 1 female Experiment Overall Design: Global gene expression profiling was performed using Affymetrix technology. The animals used were independent of each other.
2008-10-25 | E-GEOD-12707 | biostudies-arrayexpress
Project description:Skin is the largest organ in the body and comprises several types of cells. The intercellular plasticity of keratinocytes, fibroblasts, and skin adipocytes contributes to wound healing and dermal adipogenesis. Although keratinocyte activates dermal adipose tissue (dWAT) differentiation upon hair follicular cycle, regulating dWAT hyperplasia through keratinocyte reprogramming is still unknown. We used the CRISPR/Cas9 base editor to induce single nucleotide polymorphisms in Forkhead-box N1 (Foxn1) and identified the p.L19M variant that induced the formation of a thicker dWAT regardless of hair follicular cycle or wound healing. Foxn1 p.L19M activates Wnt5β through transcriptional activity. Wnt5β signaling induces the conversion of dWAT dermal fibroblasts into adipose precursor cells (APCs) and promotes APC adipocyte differentiation through keratinocyte epithelial-mesenchymal transition (EMT) and adipogenic signaling. Wnt5β is involved in the entire process of dWAT hyperplasia through APC supply and adipogenic signaling as a single factor. Foxn1 p.L19M and Wnt5β are expressed in keratinocytes, and a keratinocyte-derived adipogenic signal is critical for dermal adipogenesis. In addition, transient expression of Foxn1 p.L19M or Wnt5β using adeno-associated virus reproduced dermal adipocyte hyperplasia in mice. Considering the increasing importance of dWAT in functions such as the immune response, wound healing, hair follicle growth, and temperature control, this finding has potential applications in skin regeneration
2023-08-05 | GSE239791 | GEO
Project description:The vitamin D receptor (VDR) regulates cell proliferation and differentiation including epidermal keratinocytes by modulating transcription of its target genes. We are investigating the role of VDR in epidermal stem cells and their progenies in the regeneration process of epidermis and hair in the skin. VDR null mice are utilized in which VDR is specifically deleted in keratin 14 (K14) expressing keratinocytes by Cre-lox strategy. The impact of VDR deletion was evaluated by comparison of VDR null mice with no cre littermate control mice. The VDR was abundantly expressed in potential epidermal stem cells including basal cells in interfollicular epidermis (IFE), and in CD34 expressing bulge keratinocytes in hair follicles. Gene expression profiles and subsequent pathway analysis of stem cell enriched keratinocyte populations revealed that the VDR deletion significantly suppressed β-catenin signaling as well as VDR signaling. The role of VDR in epidermal stem cells was studied during hair follicle cycling and wound healing processes. The epidermal stem cells were not appropriately stimulated by hair depilation, and did not reinitiate anagen in the hair follicles resulting in a failure of hair regrowth. In addition, the stem cells were not fully activated after full thickness wounds were generated in VDR null skin under a low calcium diet to suppress compensation pathways. Cell proliferation was not fully induced in potential stem cells located in both IFE and hair follicles near the wounding edges, and re-epithelialization rate was delayed in VDR null skin. Gene expression profiling of the wounded skin (3 days after injury) indicated that β-catenin signaling was not fully induced in VDR null skin comparable to that observed in β-catenin null mice. The β-catenin target genes including Axin2 and cell cycle regulators involved in epidermal stem cell function were not induced in the edges of the wound of VDR null skin. These results demonstrated that VDR plays an essential role in hair cycling and wound healing processes through regulation of β-catenin signaling in epidermal stem cells and their progenies. n=3 CON and KO (each sample contain RNA isolated from wounded or nonwounded skins excised from 3 mice)
2015-07-31 | E-GEOD-68727 | biostudies-arrayexpress