Distinct roles of SOX9 in self-renewal of progenitors and mesenchymal transition of the endothelium.

Regenerative capabilities of the endothelium rely on vessel-resident progenitors termed endothelial colony forming cells (ECFCs). This study aimed to investigate if these progenitors are impacted by conditions (i.e.

Epidermal mutation accumulation in photodamaged skin is associated with skin cancer burden and can be targeted through ablative therapy.

The main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear.

Subtype-Specific Analyses Reveal Infiltrative Basal Cell Carcinomas Are Highly Interactive with their Environment.

Little is known regarding the molecular differences between basal cell carcinoma (BCC) subtypes, despite clearly distinct phenotypes and clinical outcomes. In particular, infiltrative BCCs have poorer clinical outcomes in terms of response to therapy and propensity for dissemination. In this project, we aimed to use exome sequencing and RNA sequencing to identify somatic mutations and molecular pathways leading to infiltrative BCCs.

Whole-mount staining coupled to a UV-inducible basal cell carcinoma murine model.

The origin of basal cell carcinomas (BCC) remains elusive. This protocol combines the use of an ultraviolet (UV)-inducible BCC murine model (K14CrexPtch) and an optimized protocol for florescent whole-mount cytokeratin 17 immunostaining to address the spatiotemporal dynamics of BCC formation. The high-resolution three-dimensional confocal images are an excellent tool to visualize and quantify the distribution of skin cancers at a given time point.

Regional Variation in Epidermal Susceptibility to UV-Induced Carcinogenesis Reflects Proliferative Activity of Epidermal Progenitors.

To better understand the influence of ultraviolet (UV) irradiation on the initial steps of skin carcinogenesis, we examine patches of labeled keratinocytes as a proxy for clones in the interfollicular epidermis (IFE) and measure their size variation upon UVB irradiation. Multicolor lineage tracing reveals that in chronically irradiated skin, patches near hair follicles (HFs) increase in size, whereas those far from follicles do not change. This is explained by proliferation of basal epidermal cells within 60 μm of HF openings.

Ectopic expression of SOX18 in Basal cell carcinoma negatively regulates tumour progression.

Background: Basal Cell Carcinoma is the most common tumour and yet much remains to be determined regarding the molecular mechanisms that leads to its development. Hedgehog signal activation is sufficient for BCC induction, but the molecular mediators of BCC growth are not well understood. SoxF transcription factor Sox18 has been identified in human BCC, but its role in growth of the tumour is as yet unknown.

Immunosuppression Agent Cyclosporine Reduces Self-Renewal and Vessel Regeneration Potentiation of Human Endothelial Colony Forming Cells.

Endothelial colony forming cells (ECFC) and mesenchymal stem cells (MSC) combined have great potential to be used for cell therapy of ischemic vascular diseases. However, to improve allogeneic stem cell engraftment the use of immunosuppression, such as cyclosporine has been suggested. Our aim was to assess the impact of cyclosporine on hind limb revascularisation upon MSC and ECFC combination therapy.

Whole-Mount Immunofluorescent Staining Coupled to Multicolor Lineage Tracing Model for Analyzing the Spatiotemporal Organization of Epidermal Stem Cells.

An overall three-dimensional picture of the distribution of epidermal cells at a given time point is of importance to better characterize epidermal progenitors. We introduce a whole-mount immunofluorescent staining coupled to a multicolor lineage tracing model for analyzing the spatiotemporal organization of epidermal stem cells. Laser scanning confocal microscopy with multiple labelling allows for robust imaging of dorsal skin with excellent resolution.

Past stem cells and finally in transit: SLC1A3 instructs skin niche coupling.

During postnatal growth of the skin and homeostatic hair cycling, different proliferative compartments contribute to tissue expansion and establishment of a functional epidermis. A new study by Reichenbach (2018) reports coordinated proliferation of three distinct epithelial stem cell niches and a role for glutamate transporter Slc1a3 in synchronisation of activated stem and progenitor cells.

Igf1r signalling acts on the anagen-to-catagen transition in the hair cycle.

Insulin-like growth factor 1 (Igf1) is important for skin development and homoeostasis. However, overexpression and inactivation studies have produced variable findings regarding its role in hair follicle (HF) biology. Here, we studied a conditional and inducible knockout of the Igf1 receptor (Igf1r) in keratin 15-expressing bulge cells.

Bimodal behaviour of interfollicular epidermal progenitors regulated by hair follicle position and cycling.

Interfollicular epidermal (IFE) homeostasis is a major physiological process allowing maintenance of the skin barrier function. Despite progress in our understanding of stem cell populations in different hair follicle compartments, cellular mechanisms of IFE maintenance, in particular, whether a hierarchy of progenitors exists within this compartment, have remained controversial. We here used multicolour lineage tracing with Brainbow transgenic labels activated in the epidermis to track individual keratinocyte clones.

STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction.

Hair follicles are skin appendages that undergo periods of growth (anagen), regression (catagen), and rest (telogen) regulated by their mesenchymal component, the dermal papilla (DP). On the basis of the reports of its specific expression in the DP, we investigated signal transducer and activator of transcription (STAT5) activation during hair development and cycling. STAT5 activation in the DP began in late catagen, reaching a peak in early anagen before disappearing for the rest of the cycle.

Concise review: understanding clonal dynamics in homeostasis and injury through multicolor lineage tracing.

Lineage tracing is an essential tool to study stem cell fate. Although traditional lineage tracing techniques have considerably advanced our understanding of stem cell behavior, they pose significant limitations for identification and longitudinal tracking of the progeny of individual stem cells, to compare their behaviors. This is of importance given the well-established heterogeneity among stem cells both in terms of potentialities and proliferative capacities.

Transgenic flash mice for in vivo quantitative monitoring of canonical Wnt signaling to track hair follicle cycle dynamics.

Hair follicles (HFs) upon development enter a lifelong cycle of growth, regression, and resting. These phases have been extensively studied at the cellular and molecular levels for individual HFs. However, HFs group into domains with coordinated cycling strongly influenced by their environment.

Biphasic recruitment of microchimeric fetal mesenchymal cells in fibrosis following acute kidney injury.

Fetal microchimeric cells (FMCs) enter the maternal circulation and persist in tissue for decades. They have capacity to home to injured maternal tissue and differentiate along that tissue's lineage. This raises the question of the origin(s) of cells transferred to the mother during pregnancy.

Distant mesenchymal progenitors contribute to skin wound healing and produce collagen: evidence from a murine fetal microchimerism model.

The contribution of distant and/or bone marrow-derived endogenous mesenchymal stem cells (MSC) to skin wounds is controversial. Bone marrow transplantation experiments employed to address this have been largely confounded by radiation-resistant host-derived MSC populations. Gestationally-acquired fetal MSC are known to engraft in maternal bone marrow in all pregnancies and persist for decades.

Specific maternal microchimeric T cells targeting fetal antigens in β cells predispose to auto-immune diabetes in the child.

Objective: During pregnancy there is an exchange of cells between the fetus and the mother including T lymphocytes that can persist after delivery. Previous studies have described an increased numbers of maternal cells in children with juvenile diabetes as compared to their unaffected siblings. Our objective was to assess the possibility for these chimeric T cells to trigger an anti-beta cell response.

Fine tuning of the threshold of T cell selection by the Nck adapters.

Thymic selection shapes the T cell repertoire to ensure maximal antigenic coverage against pathogens while preventing autoimmunity. Recognition of self-peptides in the context of peptide-MHC complexes by the TCR is central to this process, which remains partially understood at the molecular level. In this study we provide genetic evidence that the Nck adapter proteins are essential for thymic selection.

Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire.

The size and sensitivity of the T-cell repertoire governs the effectiveness of immune responses against invading pathogens. Both are modulated by T-cell receptor (TCR) activity through molecular mechanisms, which remain unclear. Here, we provide genetic evidence that the SH2/SH3 domain containing proteins Nck lower the threshold of T-cell responsiveness.