Ontology highlight
ABSTRACT:
PROVIDER: PRJEB48457 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR7196780.fastq.gz | Fastqsanger.gz | |||
| ERR7196781.fastq.gz | Fastqsanger.gz | |||
| ERR7196782.fastq.gz | Fastqsanger.gz | |||
| ERR7196783.fastq.gz | Fastqsanger.gz | |||
| ERR7196784.fastq.gz | Fastqsanger.gz |
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Project description:Ultraviolet-B irradiation (UVB) induces an epidermal damage response including keratinocyte hyperplasia, immune cell infiltration, and the recruitment of follicular melanocyte stem cells to the interfollicular epidermis. Here, we establish the oncofetal chromatin remodeling factor High mobility group AT-hook 2 (Hmga2) as a regulator of these phenotypes through a cyclic-AMP (cAMP) driven process. In this study, we identify somatic tissue expression of Hmga2 in the basal layer of hyperplastic UVB-exposed keratinocytes. Loss of Hmga2 results in the near absence of epidermal hyperplasia, cutaneous neutrophil infiltration, and melanocyte stem cell migration to the interfollicular epidermis. RNAseq of UVB-exposed keratinocytes from wild-type and Hmga2 loss-of-function models reveals increased expression of Adenosine A1 receptor (Adora1), a negative regulator of cAMP. Administration of the cAMP pathway activator forskolin to Hmga2-/- animals is sufficient to rescue McSC migration, thus highlighting the Hmga2-cAMP axis as a regulator in the cutaneous UVB response.
2026-05-14 | GSE331027 | GEO
Project description:RNA sequencing was performed on sorted populations of Lgr6-positive and Lgr6-negative keratinocytes from the interfollicular epidermis and the hair follicle/sebaceous gland, in order to determine the compartment-specific expression signatures of Lgr6+ progenitor cells.
2015-10-22 | E-MTAB-3533 | biostudies-arrayexpress
Project description:To investigate whether cutaneous melanoma originates from a resident adult melanocyte stem cell (MSC) or a mature melanocyte, we created a model that recapitulates key histopathological features of human melanomagenesis by inducing a BRafV600E-driven melanomagenic program in interfollicular (IF) melanocytes located in mouse tails. To this end, we sequenced the transcriptome of FACS-sorted individual IFE reporter-positive cells from BRaf/Pten/tdTomato mice, the tails of which had been painted with 4-HT for 31 and 72 days, respectively. These time points were chosen as melanoma cells are exclusively found in the IF epidermis at day 31 (d31) and in both epidermis and dermis at day 72 (d72). Normal IF melanocytes from Tyr::CreERT2/+; ROSA26RLSL-tdTomato/+ were also isolated and profiled These data indicated that loss of differentiation markers occurs in a subset of targeted epidermal melanoma cells before the onset of dermal invasion and that this event may, at least partly, be a consequence of induction of Zeb1 expression.
2017-11-16 | GSE100607 | GEO
Project description:Human epidermis is colonized by clones carrying UV light induced p53 mutations, thought to be the origin of keratinocyte derived cancers, but the cellular mechanisms underlying the formation of these clones are not well understood. To address this we generated a new conditional knock-in mouse model bearing one of the hot spot mutations, R245W (R248W in human), targeted to the p53 locus, with its expression linked to a GFP reporter to enable lineage tracing. This mutation is one of the most frequently observed in cutaneous squamous cell carcinomas. We find that when induced in individual epidermal interfollicular progenitor cells the p53 mutant cells are dominant over wild type keratinocytes expanding to colonize the majority of the interfollicular epidermis. This process is accelerated by sub erythema doses ultraviolet light exposure. In vitro analysis of the trancriptomes can explain the intrinsic function driving clonal expansion.
2018-10-31 | E-MTAB-4941 | biostudies-arrayexpress
Project description:Cursons2015 - Regulation of ERK-MAPK
signaling in human epidermis
Model comparing the abundance of
phosphorylated MAPK signalling proteins and calcium signalling in
the epidermis.
This model is described in the article:
Regulation of ERK-MAPK
signaling in human epidermis.
Cursons J, Gao J, Hurley DG, Print
CG, Dunbar PR, Jacobs MD, Crampin EJ.
BMC Syst Biol 2015; 9: 41
Abstract:
The skin is largely comprised of keratinocytes within the
interfollicular epidermis. Over approximately two weeks these
cells differentiate and traverse the thickness of the skin. The
stage of differentiation is therefore reflected in the
positions of cells within the tissue, providing a convenient
axis along which to study the signaling events that occur in
situ during keratinocyte terminal differentiation, over this
extended two-week timescale. The canonical ERK-MAPK signaling
cascade (Raf-1, MEK-1/2 and ERK-1/2) has been implicated in
controlling diverse cellular behaviors, including proliferation
and differentiation. While the molecular interactions involved
in signal transduction through this cascade have been well
characterized in cell culture experiments, our understanding of
how this sequence of events unfolds to determine cell fate
within a homeostatic tissue environment has not been fully
characterized.We measured the abundance of total and
phosphorylated ERK-MAPK signaling proteins within
interfollicular keratinocytes in transverse cross-sections of
human epidermis using immunofluorescence microscopy. To
investigate these data we developed a mathematical model of the
signaling cascade using a normalized-Hill differential equation
formalism.These data show coordinated variation in the
abundance of phosphorylated ERK-MAPK components across the
epidermis. Statistical analysis of these data shows that
associations between phosphorylated ERK-MAPK components which
correspond to canonical molecular interactions are dependent
upon spatial position within the epidermis. The model
demonstrates that the spatial profile of activation for
ERK-MAPK signaling components across the epidermis may be
maintained in a cell-autonomous fashion by an underlying
spatial gradient in calcium signaling.Our data demonstrate an
extended phospho-protein profile of ERK-MAPK signaling cascade
components across the epidermis in situ, and statistical
associations in these data indicate canonical ERK-MAPK
interactions underlie this spatial profile of ERK-MAPK
activation. Using mathematical modelling we have demonstrated
that spatially varying calcium signaling components across the
epidermis may be sufficient to maintain the spatial profile of
ERK-MAPK signaling cascade components in a cell-autonomous
manner. These findings may have significant implications for
the wide range of cancer drugs which therapeutically target
ERK-MAPK signaling components.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000659.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000659 | BioModels
Project description:To better understand the homeostatic mechanisms governing melanocytes, we performed deep phenotyping of single-cell expansions of melanocytes from human skin. In total, we interrogated the mutational landscapes, gene expression profiles, and morphological features of 297 melanocytes from 31 donors. To our surprise, a population of melanocytes with low mutation burden was maintained in sun damaged skin. These melanocytes were more stem-like, smaller, and less dendritic than their counterparts with high mutation burdens. We used single-cell spatial transcriptomics (10X Xenium) to reveal the spatial distribution of melanocytes inferred to have low and high mutation burdens (LowMut and HighMut cells), based on their gene expression profiles. LowMut melanocytes were found in hair follicles as well as in the interfollicular epidermis, whereas HighMut melanocytes resided almost exclusively in the interfollicular epidermis. We propose that melanocytes in the hair follicle occupy a privileged niche, protected from UV radiation, but periodically migrate out of the hair follicle to replenish the interfollicular epidermis after waves of photodamage. More broadly, our study illustrates the advantages of a cell atlas that includes mutational information, as cells can change their cellular states and positional coordinates over time, but mutations are like scars, providing a historical record of the homeostatic processes that were operative on each cell.
2025-02-13 | GSE286964 | GEO
Project description:The skin’s continuous renewal relies on stem and progenitor cells, yet their differential susceptibility to oncogenic mutations in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Rapid cSCC development occurs in melanoma patients treated with BRAF inhibitors, driven by paradoxical MAPK activation. To model this in mice, we use two complementary approaches: HRASG12V with BRAFi to mimic paradoxical MAPK activation, and BRAFV600E, which drives MAPK hyperactivation without further treatment. We target these mutations to the interfollicular stem and differentiation-committed progenitors of the basal epidermis. While stem cells rapidly form tumours, progenitors exhibit long-latency resistance despite retaining mutations and repopulating the basal layer. Ultimately, both populations produce similar tumours, revealing a shared transformation programme. However, SOX2 is uniquely upregulated in tumours from the progenitor population. SOX2 is expressed in 20% of human cSCC, suggesting that it could mark tumours originating from committed progenitors. Here, we show that SOX2 overexpression in progenitors induces a stem-like state and renders this otherwise resistant population permissive to transformation.
2025-10-20 | GSE303703 | GEO
Project description:The skin’s continuous renewal relies on stem and progenitor cells, yet their differential susceptibility to oncogenic mutations in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Rapid cSCC development occurs in melanoma patients treated with BRAF inhibitors, driven by paradoxical MAPK activation. To model this in mice, we use two complementary approaches: HRASG12V with BRAFi to mimic paradoxical MAPK activation, and BRAFV600E, which drives MAPK hyperactivation without further treatment. We target these mutations to the interfollicular stem and differentiation-committed progenitors of the basal epidermis. While stem cells rapidly form tumours, progenitors exhibit long-latency resistance despite retaining mutations and repopulating the basal layer. Ultimately, both populations produce similar tumours, revealing a shared transformation programme. However, SOX2 is uniquely upregulated in tumours from the progenitor population. SOX2 is expressed in 20% of human cSCC, suggesting that it could mark tumours originating from committed progenitors. Here, we show that SOX2 overexpression in progenitors induces a stem-like state and renders this otherwise resistant population permissive to transformation.
2025-10-20 | GSE280236 | GEO
Project description:Mammalian epidermis consists of three self-renewing compartments: the hair follicle, sebaceous gland and interfollicular epidermis. We generated knock-in alleles of murine Lgr6, a close relative to the Lgr5 stem cell gene. Lgr6 was expressed in the earliest embryonic hair placodes. In adult hair follicles, Lgr6+ cells resided in a previously uncharacterized region directly above the follicle bulge. They expressed none of the known bulge stem cell markers. Prenatal Lgr6+ cells established the hair follicle, sebaceous gland and interfollicular epidermis. Postnatally, Lgr6+ cells generated sebaceous gland and interfollicular epidermis, while contribution to hair lineages gradually diminished with age. Adult Lgr6+ cells executed long-term wound repair, including the formation of new hair follicles. We conclude that Lgr6 marks the most primitive epidermal stem cell.
2010-03-26 | GSE20269 | GEO
Project description:SMARTseq2 scRNAseq of interfollicular epidermis basal cells at P20
2020-04-16 | GSE122817 | GEO