The impact of HPV8 E6 on Lrig1+ hair follicle junctional zone expansion
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB68192 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Despite epidermal turnover, the skin is host to a complex array of microbes including viruses, such as the human papillomavirus (HPV), which must infect and manipulate skin keratinocyte stem cells (KSC) to survive. This crosstalk between the virome and KSC populations remains largely unknown. Here, we investigated the effect of HPV8 on KSCs using various mouse models. We observed that the HPV8 early region gene E6 specifically caused Lrig1+hair follicle junctional zone KSC proliferation and expansion, which would facilitate viral transmission. Within Lrig1+KSCs specifically, HPV8 E6 bound intracellular p300 to phosphorylate the STAT3 transcriptional regulatory node. This induces a transcriptional switch from TAp63 to ΔNp63 expression, resulting in expansion of KSC into the overlying epidermis. HPV8 was associated with 70% of human actinic keratoses (AK). Together these results redefine human AK as an expansion of KSC, which lack protecting melanosomes and are thus susceptible to sun-light-induced malignant transformation.
2024-02-22 | GSE247466 | GEO
Project description:Despite epidermal turnover, the skin is host to a complex array of microbes including viruses, such as the human papillomavirus (HPV), which must infect and manipulate skin keratinocyte stem cells (KSC) to survive. This crosstalk between the virome and KSC populations remains largely unknown. Here, we investigated the effect of HPV8 on KSCs using various mouse models. We observed that the HPV8 early region gene E6 specifically caused Lrig1+hair follicle junctional zone KSC proliferation and expansion, which would facilitate viral transmission. Within Lrig1+KSCs specifically, HPV8 E6 bound intracellular p300 to phosphorylate the STAT3 transcriptional regulatory node. This induces a transcriptional switch from TAp63 to ΔNp63 expression, resulting in expansion of KSC into the overlying epidermis. HPV8 was associated with 70% of human actinic keratoses (AK). Together these results redefine human AK as an expansion of KSC, which lack protecting melanosomes and are thus susceptible to sun-light-induced malignant transformation.
2024-06-03 | GSE247569 | GEO
Project description:Tfap2c is deleted in Tpbpa positive precursor cells forming the junctional zone of murine placenta. Deregulation in gene expression is analysed compared to the junctional zone in control placenta.
2016-01-31 | GSE70962 | GEO
Project description:To characterise the transcriptome of mouse placental junctional zone cells in Control litters (deletion of the maternally-inherited and silent Igf2 allele, with normal Igf2 levels in whole litters) in UE litters (dams carried offspring with a deletion of the paternally-inherited Igf2 allele in the placental endocrine cells with diminished Igf2 production from the endocrine cells in whole litters), we performed single nucleus RNA sequencing on the placenta Junctional zone 8 Control placentas (offspring sex: 4M:4F) and 8 UE placentas (offspring sex: 4M:4F) in 2 batches each.
2023-04-30 | GSE229514 | GEO
Project description:Regulatory T cell (Treg) is the immune-suppressive T cell subset and the crucial component for preventing autoimmunity. The molecules defining the suppressive population of T cells phenotypically and functionally remain to be discovered. In this study, we report that Lrig1 is highly expressed in suppressive CD4+ T cell populations. We performed RNA-seq analysis of CD4+Lrig1+ and CD4+Lrig1- T cells from mouse splenocytes to analyze the genes involeved in the suppressive function of T cells.
2023-07-16 | GSE236988 | GEO
Project description:As LRIG1 known to be a negative regulator of EGFR, we postulate that restored LRIG1 expression will change the transcription profile through the regulation of EGFR as well as its downstream signal cascades. Thus, we conducted a time-course microarray study to examine the effect of restored LRIG1 expression in NPC line, TW01-LG1/a, which the LRIG1 expression is under the control of a promoter with Doxycycline response element. We established stable transfectants of the LRIG1 gene in the TW01 cells which the expression of LRIG1 protein was barely detectable. To control the expression of LRIG1, the coding sequences were placed under the control of a promoter with doxycycline (Dox)-response element using the Tetoff system. Thus the LRIG1 expression could be turn on by removing Dox from the culture medium. Cellular total RNA were harvested along a time course of 12, 24, 36, and 48 hr following LRIG1 turn on expression, and then subjected to exon array analysis (Affymatrix Human Gene 1.0 ST), using the LRIG1 non-expressing sample (with Dox) as control for all comparison. For each time-point, a biological replicate was included.
2013-05-02 | E-GEOD-37349 | biostudies-arrayexpress
Project description:Gata6 network regulates epidermal junctional zone cell fate.
| PRJNA264527 | ENA
Project description:Cancer immunotherapies boost antitumor immunity and improve the survival of cancer patients. V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an immune 20 checkpoint target but presents elusive signaling mechanisms. We report a novel VISTA binding partner, Leucine-Rich Repeats and Immunoglobulin Like Domains 1 (LRIG1), which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell-specific LRIG1 deletion developed superior antitumor T cell responses. Mechanistically, LRIG1-deficient tumor-specific CD8+ cytotoxic T cells (CTLs) exhibited longer 25 persistence due to improved expansion and survival and greater effector function. Sustained tumor control was also associated with a reduction of quiescent CTLs (TCF1+ CD62Lhi PD-1low) and a reciprocal increase in progenitor and memory-like CTLs (TCF1+ PD-1+). In human melanoma, an elevated LRIG1 expression on tumor-infiltrating CD8+ CTLs correlated with resistance to immunotherapies. Taken together, these results delineate the role of LRIG1 as an inhibitory 30 immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy.
2024-10-17 | PXD050084 | Pride
Project description:As LRIG1 known to be a negative regulator of EGFR, we postulate that restored LRIG1 expression will change the transcription profile through the regulation of EGFR as well as its downstream signal cascades. Thus, we conducted a time-course microarray study to examine the effect of restored LRIG1 expression in NPC line, TW01-LG1/a, which the LRIG1 expression is under the control of a promoter with Doxycycline response element.
2013-05-02 | GSE37349 | GEO