Dataset Information

JunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin.

ABSTRACT: Transcription factors ensure skin homeostasis via tight regulation of distinct resident stem cells. Here we report that JunB, a member of the AP-1 transcription factor family, regulates epidermal stem cells and sebaceous glands through balancing proliferation and differentiation of progenitors and by suppressing lineage infidelity. JunB deficiency in basal progenitors results in a dermatitis-like syndrome resembling seborrheic dermatitis harboring structurally and functionally impaired sebaceous glands with a globally altered lipid profile. A fate switch occurs in a subset of JunB deficient epidermal progenitors during wound healing resulting in de novo formation of sebaceous glands. Dysregulated Notch signaling is identified to be causal for this phenotype. In fact, pharmacological inhibition of Notch signaling can efficiently restore the lineage drift, impaired epidermal differentiation and disrupted barrier function in JunB conditional knockout mice. These findings define an unprecedented role for JunB in epidermal-pilosebaceous stem cell homeostasis and its pathology.

SUBMITTER: Singh K

PROVIDER: S-EPMC6109099 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

JunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin.

Singh Karmveer K Camera Emanuela E Krug Linda L Basu Abhijit A Pandey Rajeev Kumar RK Munir Saira S Wlaschek Meinhard M Kochanek Stefan S Schorpp-Kistner Marina M Picardo Mauro M Angel Peter P Niemann Catherin C Maity Pallab P Scharffetter-Kochanek Karin K

Nature communications 20180824 1

Transcription factors ensure skin homeostasis via tight regulation of distinct resident stem cells. Here we report that JunB, a member of the AP-1 transcription factor family, regulates epidermal stem cells and sebaceous glands through balancing proliferation and differentiation of progenitors and by suppressing lineage infidelity. JunB deficiency in basal progenitors results in a dermatitis-like syndrome resembling seborrheic dermatitis harboring structurally and functionally impaired sebaceous ...[more]

PMID: 30143626

Similar Datasets

Project description:Lymphatic structure and function play a critical role in fluid transport, antigen delivery, and immune homeostasis. A dysfunctional lymphatic system is associated with chronic low-grade inflammation of peripheral tissues, poor immune responses, and recurrent infections, which are also hallmarks of aging pathology. Previous studies have shown that aging impairs lymphatic structure and function in a variety of organ systems, including the intestines and central nervous system. However, previous studies are mostly limited to qualitative analysis of lymphatic structural changes and quantification of intestinal collecting vessel contractile function. It is not clear whether decreased lymphatic function contributes to pathological conditions related to aging, nor how it affects the skin immune microenvironment. Further, the effects of aging on skin initial and collecting lymphatic vessels, dendritic cell (DC) migration, cutaneous lymphatic pumping, and VEGFR-3 signaling in lymphatic endothelial cells (LECs) have not been quantitatively analyzed. Here, using fluorescent immunohistochemistry and flow cytometry, we confirm that aging decreases skin initial and collecting lymphatic vessel density. Indocyanine green (ICG) lymphangiography and DC migration assays confirm that aging decreases both fluid pumping and cell migration via lymphatic vessels. At the cellular level, aging causes decreased VEGFR-3 signaling, leading to increased LEC apoptosis and senescence. Finally, we determined that aging causes decreased lymphatic production of chemokines and alters LEC expression of junctional and adhesion molecules. This in turn leads to increased peri-lymphatic inflammation and nitrosative stress that might contribute to aging pathology in a feed-forward manner. Taken together, our study, in addition to quantitatively corroborating previous findings, suggests diverse mechanisms that contribute to lymphatic dysfunction in aging that in turn exacerbate the pathology of aging in a feed-forward manner.

Project description:ObjectivesRecovery from coma might critically depend on the structural and functional integrity of frontoparietal networks. We aimed to measure this integrity in traumatic brain injury and anoxo-ischemic (cardiac arrest) coma patients by using an original multimodal MRI protocol.DesignProspective cohort study.SettingThree Intensive Critical Care Units affiliated to the University in Toulouse (France).PatientsWe longitudinally recruited 43 coma patients (Glasgow Coma Scale at the admission < 8; 29 cardiac arrest and 14 traumatic brain injury) and 34 age-matched healthy volunteers. Exclusion criteria were disorders of consciousness lasting more than 30 days and focal brain damage within the explored brain regions. Patient assessments were conducted at least 2 days (5 ± 2 d) after complete withdrawal of sedation. All patients were followed up (Coma Recovery Scale-Revised) 3 months after acute brain injury.InterventionsNone.Measurements and main resultsFunctional and structural MRI data were recorded, and the analysis was targeted on the posteromedial cortex, the medial prefrontal cortex, and the cingulum. Univariate analyses and machine learning techniques were used to assess diagnostic and predictive values. Coma patients displayed significantly lower medial prefrontal cortex-posteromedial cortex functional connectivity (area under the curve, 0.94; 95% CI, 0.93-0.95). Cardiac arrest patients showed specific structural disturbances within posteromedial cortex. Significant cingulum architectural disturbances were observed in traumatic brain injury patients. The machine learning medial prefrontal cortex-posteromedial cortex multimodal classifier had a significant predictive value (area under the curve, 0.96; 95% CI, 0.95-0.97), best combination of subregions that discriminates a binary outcome based on Coma Recovery Scale-Revised).ConclusionsThis exploratory study suggests that frontoparietal functional disconnections are specifically observed in coma and their structural counterpart provides information about brain injury mechanisms. Multimodal MRI biomarkers of frontoparietal disconnection predict 3-month outcome in our sample. These findings suggest that fronto-parietal disconnection might be particularly relevant for coma outcome prediction and could inspire innovative precision medicine approaches.

Project description:ObjectiveStudies on upper limb recovery following stroke have highlighted the importance of the structural and functional integrity of the corticospinal tract (CST) in determining clinical outcomes. However, such relationships have not been fully explored for the lower limb. We aimed to test whether variation in walking impairment was associated with variation in the structural or functional integrity of the CST.MethodsTranscranial magnetic stimulation was used to stimulate each motor cortex while EMG recordings were taken from the vastus lateralis (VL) bilaterally; these EMG measures were used to calculate both ipsilateral and contralateral recruitment curves for each lower limb. The slope of these recruitment curves was used to examine the strength of functional connectivity from the motor cortex in each hemisphere to the lower limbs in chronic stroke patients and to calculate a ratio between ipsilateral and contralateral outputs referred to as the functional connectivity ratio (FCR). The structural integrity of the CST was assessed using diffusion tensor MRI to measure the asymmetry in fractional anisotropy (FA) of the internal capsule. Lower limb impairment and walking speed were also measured.ResultsThe FCR for the paretic leg correlated with walking impairment, such that greater relative ipsilateral connectivity was associated with slower walking speeds. Asymmetrical FA values, reflecting reduced structural integrity of the lesioned CST, were associated with greater walking impairment. FCR and FA asymmetry were strongly positively correlated with each other.ConclusionsPatients with relatively greater ipsilateral connectivity between the contralesional motor cortex and the paretic lower limb were more behaviorally impaired and had more structural damage to their ipsilesional hemisphere CST.SignificanceMeasures of structural and functional damage may be useful in the selection of therapeutic strategies, allowing for more tailored and potentially more beneficial treatments.

Dataset Information

JunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin.

Publications

JunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets