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Hair follicle-associated-pluripotent (HAP) stem cells are located in the bulge area of the hair follicle, express the stem-cell marker nestin, and have been shown to differentiate to neurons, glial cells, keratinocytes, smooth muscle cells, melanocytes and cardiac muscle cells. Transplanted HAP stem cells promoted the recovery of peripheral nerve and spinal cord injuries and have the potential for heart regeneration as well. In the present study, we implanted mouse green fluorescent protein (GFP)-expressing HAP stem-cell spheres captured on polyvinylidene fluoride membranes (PFM) into the severed thoracic spinal cord.
In anagen hair follicles, multipotent stem cells are believed to be preserved only in the bulge region. Due to the rapidly proliferative character, anagen hair follicles are highly sensitive to genotoxic chemotherapeutic agents, leading to a dystrophic response with hair loss. How the lost structures are regenerated to resume anagen growth is unclear. We induced a dystrophic anagen response by cyclophosphamide in mice and found that basal lower proximal cup cells were quickly activated to repair damaged hair bulbs.
Previously, we revealed how the underlying molecular mechanism of Bone Morphogenetic Protein (BMP) signaling governs the homeostasis of hair follicle stem cells (hfSCs) in vivo. Here, we focused on testing role of Id2 gene, one of the target genes which we identified to be downregulated in hfSCs after inhibition of BMP pathway. To test the function of Id2 gene in hfSCs in vivo we used Id2 gain of function approach (GOF) by generating transgenic mouse line. Our data demonstrated that Id2 overexpression in hfSCs results in prolonged telogen and a delay in anagen activation, maintaining stem cells quiescence.
TRPV3, a member of the transient receptor potential (TRP) family, is a non-selective cation channel. Gain-of-function mutated protein, such as TRPV3G568V, is constitutively open. TRPV3G568V mice show not only periodical hair loss and shortened telogen, but also thickened interfollicular epidermis (IFE) and immune cells infiltration in dermis. Hair follicle morphogenesis is normal, but the hairs cant smoothly penetrate the epidermis, thus become twisted. Why? RNAscope shows that TRPV3 mRNA is highly expressed in hair follicles rather than other parts, indicating that hair follicle abnormity may be a primary event.
Hair follicle formation during skin development requires interactions between epithelial progenitors and a progressively differentiating dermal fibroblast population. Heterogenous fibroblasts originate from a homogenous mesenchyme and become lineage committed after E16.5 days. Hair follicle formation begins at ∼E14.5, which is prior to fibroblast lineage commitment, suggesting that this time point holds the highest potential for fibroblasts to become dermal papilla. We tested the hypothesis that undifferentiated embryonic fibroblasts (E14.5) possess an enhanced ability to support de novo hair follicle formation, utilizing the chamber grafting assay.
Production and release of sebum on skin surface ensures skin suppleness and contributes to its intact barrier function. With increasing age this function is disturbed leading to dryer skin and high susceptibility to microbial infections. Knowledge regarding the regulation of lipogenesis in sebocytes and subsequent release of sebum components through apoptosis still remains sparse. In this study, we focused on the apoptotic response of human SZ95 sebocytes to four biologically relevant fatty acids (FA), arachidonic acid (AA), linoleic acid (LA), palmitic acid (PA) and palmitoleic acid (POA).
Merkel cells (MC) are innervated light touch sensors that comprise less than 0.3% of the mouse epidermis. Study of MC development provides a model of lineage-specific epithelial differentiation and gives insight into the tumorigenesis of Merkel cell carcinoma (MCC). Single-cell RNA sequencing (scRNA-seq) allows high-resolution transcriptomic analysis of lineage-specific developmental programs. We developed a protocol to isolate single GFP-labeled MC from mouse epidermis at different developmental stages.
Specialized mesenchymal cells in dermal condensates (DC) play a crucial role in regulating hair follicle (HF) progenitors in epidermal placodes (Pc) to orchestrate HF morphogenesis. Nevertheless, to date the inductive signals during DC specification and how DC cells interplay with Pc progenitors to facilitate HF development remain unknown. Here we identify precursor cells of the DC (pre-DC) before it appears as specialized cell cluster. With fluorescence-activated cell sorting we co-isolate pre-DC and the DC as it matures, together with the Pc at stage 0 HFs, and other lineage-related populations.
Trichodysplasia spinulosa (TS) is a rare hair follicle disorder that develops in immunosuppressed patients and is associated with productive infection by a polyomavirus designated TSPyV. TS presents as numerous minute papules, some with a central keratotic spicule, typically on the face and ears. TS hair follicles are dysmorphic, consisting of outer root sheath, companion layer, hair matrix, an expanded inner root sheath (IRS) compartment, and a poorly-formed hair shaft that may produce a clinically apparent spicule.
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease resulting from a lack of type VII collagen production. Recent clinical trials have shown efficacy of bone marrow-derived stem cells (BM-MSCs) in the treatment of epidermolysis bullosa, including improved basement membrane restructuring and cutaneous wound healing. The mechanism as to how type VII collagen is transferred from donor stem cell to recipient RDEB cells has not been defined. Here, we report that BM-MSC-derived extracellular vesicles serve at least two roles: 1) to help transport the insoluble type VII collagen alpha chains within the extracellular space; and 2) to feed RDEB fibroblasts with messenger RNA that codes for type VII collagen, resulting in COL7A1 translation and synthesis of normal type VII collagen alpha chain proteins, eventually secreted by RDEB fibroblasts.
Premature canitie and greying hair pigmentation are phenomenons directly linked to a melanin lack in the hair bulb but also to the accumulation of hydrogen peroxide (H2O2) in hair follicles. To counteract these processes, we have developed a biomimetic peptide of the α-MSH (palmitoyl tetrapeptide-20), enables to promote in vitro, ex vivo and in vivo hair pigmentation and reduce hair greying process. In vitro studies revealed the peptide capacity to increase melanin synthesis by 39% in human melanocytes and melanosome transfer to keratinocytes by 50%.
The role of the extracellular matrix (ECM) in the regulation of epidermal homeostasis is not clearly known. Here, we observed that no hyaluronate (HA) is detected in the epidermal ECM in CD44KO mice, while the EGFR antagonist Lrig1+ stem cell compartment was atrophic, suggesting that HA interaction with its main keratinocyte receptor, CD44, may regulate epidermal growth. We further explored in human keratinocytes whether Lrig1 could regulate the previously described hyalurosome, a molecular platform anchored on filopodia.
As new cells are generated in the skin, older cells must transit out of the basal layer in order to maintain homeostasis. Cells may be lost through apoptosis, but maintenance of a constant basal cell number is primary mediated through differentiation and delamination. The cellular mechanisms that maintain homeostasis in response to uncoupling of these events are not clear. Here we show that cells reorient their division axes in response to changes in the rate of proliferation and differentiation.
Androgenetic alopecia (AGA) is a complex genetic trait that is characterized by regional hair follicle miniaturization in response to androgens. While female-pattern hair loss is characterized by a diffuse thinning of the scalp, male pattern can be induced upon elevation of testosterone levels. What confers regional susceptibility vs. refractivity on different regions of the scalp is unknown. Donor Dominance refers to the phenomenon by which hair follicles retain the characteristics of the donor site when transplanted to a recipient site.
In lesional hair follicles (HFs) of the prototypic lymphocytic scarring alopecia, lichen planopilaris (LPP), epithelial stem cells (eSCs) in the bulge lose their immune privilege, are attacked by cytotoxic CD8+T-cells, and undergo epithelial-mesenchymal-transition (EMT). This results in scarring alopecia, for which fully satisfactory therapy remains to be developed. Therefore, the current study aimed to clarify whether N-acetyl-GED (AGED), a topically applicable PPAR-γ modulator with a favorable safety profile compared to older, less selective PPAR-γ agonists like pioglitazone, can protect or rescue human HFeSCs from experimentally induced EMT and/or reverse EMT in established disease ex vivo.
Diversities in cancers pose difficulties in identifying effective therapies. Currently, it is unknown how the cell of origin influences the characteristics of melanoma, a highly heterogeneous and most dangerous cancer in the skin. Here, we introduced melanoma-forming mutations in two distinct populations of stem cells in adult mouse skin. Lineage tracing reveals that melanocyte stem cells harbored in the hair follicle possess the potential to form pigmented epidermal melanoma. In contrast, nestin positive multipotent stem cells residing in the skin dermis produce amelanotic dermal melanoma.
In our previous studies we have shown that selective in vivo suppression of CD44 in keratinocytes resulted in abnormalities in the corneal epithelium in mice. No stem cell markers have been to date identified for the corneal epithelium. However, a similar paradigm seems to exist in the bulge compartment of hair follicles in mice and the limbus of the cornea. Our preliminary studies in a group of young versus aged ocular biopsies showed that CD44 expression is downregulated in aged cornea, while the Lrig1+ stem cells are preserved in the peripheral limbus.
Frontal fibrosing alopecia (FFA) and Lichen planopilaris are inflammatory hair discorders leading to hair follicle (HF) destruction and scarring. Traditionally FFA has been regarded as a variant of lichen planopilaris (LPP) based on histological features, however, distinct phenotypic differences argue against this. So far clinicians and scientists have failed to describe the differences between each pathology. As macrophages are known scavengars of the immune system, having a role in programmed organ deletion and also are implicated in human hair cycle cotrol, they may hold the key.
In the past decade, the crosstalk between dermal white adipose tissue (DWAT) and hair follicles (HFs) has become of increasing interest. Murine studies have revealed that pathways involving BMP2, PDGFA, SHH and leptin are involved in the HF-DWAT axis. Despite such progress on murine models, human HF-DWAT communication remains virtually unexplored. In this study, we cultured micro-dissected HFs versus HFs surrounded by the immediate 3-4 layers of dermal adipocytes (HF+DWAT) from human scalp skin for 48hr ex vivo.
Cutaneous cysts have been classified by many dermatopathologists in different ways. We propose a novel classification of cutaneous adnexal cysts according to their origin in the folliculo-sebaceous unit and sweat glands. By examining the lining of the cystic structure, its origin can be easily identified. Epidermal cysts have an epithelial wall containing a granular layer and the keratinization through the lumen is lamellar, indicating an infundibular origin Tricholemmal cysts have an undulating epithelial wall with no granular layer and a compact keratinization, showing an isthmic origin.