Publications by authors named "Yuichi Hasebe"

The epidermis is an essential organ for life by retaining water and as a protective barrier. The epidermis is maintained through metabolism, in which basal cells produced from epidermal stem cells differentiate into spinous cells, granular cells and corneocytes, and are finally shed from the epidermal surface. This is epidermal turnover, and with aging, there is a decline in epidermis function.

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  • Stress can significantly affect skin conditions and aging, particularly in females, with genetic factors playing a role in individual stress responses.
  • The study analyzed 1,200 Japanese females, linking stress levels to their skin conditions and identifying specific genetic markers (SNPs) related to stress susceptibility.
  • A key finding was the SNP rs74548608, which may influence how stress is perceived, and is associated with a gene involved in cellular signaling.
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Mitochondria have their own DNA (mtDNA). Genetic variants are likely to accumulate in mtDNA, and its base substitution rate is known to be very fast, 10-20 times faster than that of nuclear DNA. For this reason, mtSNPs (mitochondrial genome single nucleotide polymorphisms) are frequently detected in mtDNA.

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  • Solar lentigo (SL) is a type of skin discoloration caused by sun exposure, characterized by excess melanin in the skin's outer layer and changes in the dermis.
  • The study found that SL lesions have reduced levels of type IV collagen, crucial for the basement membrane's structure, which affects the interaction between skin cells.
  • The research identified that while dermal stem cells can boost collagen production through exosomes, this process is impaired in SL conditions, resulting in ongoing melanin build-up in the dermis.
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The self-duplication and differentiation of dermal stem cells are essential for the maintenance of dermal homeostasis. Fibroblasts are derived from dermal stem cells and produce components of connective tissue, such as collagen, which maintains the structure of the dermis. Cell-cell communication is required for the maintenance of tissue homeostasis, and the role of exosomes in this process has recently been attracting increasing attention.

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  • Aging leads to increased levels of INHBA/Activin-A in the human epidermis, which is linked to thinning of the skin and reduced cell proliferation.
  • The study found that as INHBA/Activin-A levels rose, there was a corresponding decrease in the number of epidermal stem/progenitor cells and the overall skin thickness in older individuals.
  • Activin-A was shown to inhibit the proliferation of these stem/progenitor cells, suggesting it plays a role in age-related skin changes.
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  • Wrinkles and sagging skin are influenced by factors like UV rays and genetics, with recent studies highlighting specific genetic markers known as single nucleotide polymorphisms (SNPs) associated with these aging traits.
  • * A genome-wide association study (GWAS) was conducted on 1,041 Japanese women, discovering 5 SNPs linked to wrinkles at the outer corners of the eyes and 4 SNPs related to nasolabial folds specifically within certain genes (COL5A3 and RAD21).
  • * These newly identified SNPs provide valuable insight into the genetic factors contributing to skin aging in the Japanese population, which had limited previously reported data on this subject.
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Currently, human-skin derived cell culture is a basic technique essential for dermatological research, cellular engineering research, drug development, and cosmetic development. But the number of donors is limited, and primary cell function reduces through cell passage. In particular, since adult stem cells are present in a small amount in living tissues, it has been difficult to obtain a large amount of stem cells and to stably culture them.

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Introduction: The skin is comprised of various kinds of cells and has three layers, the epidermis, dermis and subcutaneous adipose tissue. Stem cells in each tissue duplicate themselves and differentiate to supply new cells that function in the tissue, and thereby maintain the tissue homeostasis. In contrast, senescent cells accumulate with age and secrete senescence-associated secretory phenotype (SASP) factors that impair surrounding cells and tissues, which lowers the capacity to maintain homeostasis in each tissue.

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The constitution and skin type of individuals are influenced by various factors. Recently, the influence of genetic predispositions on these has been emphasized. To date, genome-wide association studies (GWAS) have shown several single nucleotide polymorphisms (SNPs) that affect individual's constitution and skin type.

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Emerging evidence has pointed to the noxious effects of senescent cells in various tissues, and senescent cells in the epidermis are known to accumulate with age. We hypothesized that there is a mechanism by which senescent cells in the epidermis are preferentially removed and that the function of such removal mechanism declines as age increases. In this study, we investigated whether Notch signalling is involved in such senescent cell removal.

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  • Adipose-derived stromal/stem cells (ASCs) are being studied for their potential in regenerative medicine, with previous findings showing a decrease in their ability to form fat cells (adipogenesis) as people age.
  • The research focused on the impact of Gremlin 2 (GREM2), a secreted protein that inhibits stem cell differentiation; experiments showed that GREM2 levels in ASCs increase with age and negatively correlate with their adipogenic potential.
  • Results indicated that GREM2 is present in ASCs but not in fat cells, suggesting it plays a role in inhibiting fat cell development through mechanisms involving Wnt signaling pathways.
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Melanocyte stem cells (McSCs) are localized in the bulge region of hair follicles and supply melanocytes, which determine hair color by synthesizing melanin. Ectopic differentiation of McSCs, which are usually undifferentiated in the bulge region, causes depletion of McSCs and results in hair graying. Therefore, to prevent hair graying, it is essential to maintain McSCs in the bulge region, but the mechanism of McSC maintenance remains unclear.

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Hair follicle stem cells (HFSC) are localized in the bulge region of the hair follicle and play a role in producing hair. Recently, it has been shown that the number of HFSC decreases with age, which is thought to be a cause of senile alopecia. Therefore, maintaining HFSC may be key for the prevention of age-related hair loss, but the regulatory mechanisms of HFSC and the effects of aging on them are largely unknown.

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CD271 is common stem cell marker for the epidermis and dermis. We assessed a kinetic movement of epidermal and dermal CD271 cells in the wound healing process to elucidate the possible involvement with chronic skin ulcers. Epidermal CD271 cells were proliferated and migrated from 3 days after wounding.

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Stem cells have recently been shown to play important roles in wound healing. The aim of this study was to investigate the role of dermal CD271+ cells in wound healing. Full-thickness wounds were produced on the backs of 5-year-old and 24-week-old mice, and time-course of wound closure, CD271+ cell counts, and gene expression levels were compared.

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During aging, increases in the number of senescent cells are seen in various tissues. On the other hand, stem cells play crucial roles in tissue repair and homeostasis. Therefore, it is likely that stem cells give rise to new cells that replace senescent cells.

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Systemic sclerosis [scleroderma (SSc)]-associated skin fibrosis is characterized by increased fibrosis in the dermis and a reduction in the thickness of the subcutaneous adipose tissue layer. Although many studies have examined fibrosis in SSc, only a few studies have focused on the associated reduction in the thickness of the subcutaneous adipose tissue layer. In this study, we investigated the effects of SSc-induced fibrosis on adipose tissue.

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Background: In recent years, it has been reported that stem cells exist in the mesenchymal tissues of the bone marrow and adipose. These stem cells are thought to express specific cell surface markers such as CD44, CD54, CD105, CD90, and CD271 and have been confirmed to be pluripotent. Furthermore, although it has been reported that stem cells are also present in the dermis, their cell surface markers and characteristics are not fully understood.

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Background: The existence of multipotent stem cells in subcutaneous adipose tissue has been reported. We previously confirmed that p75 neurotrophin receptor (p75NTR; CD271)-positive cells in subcutaneous adipose tissue possessed multipotency, although changes of the characteristics in p75NTR-positive adipose-derived stem cells (ASCs) with aging remain unclear.

Objective: To investigate the effect of aging on p75NTR-positive ASCs.

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Thrombin-activatable fibrinolysis inhibitor (TAFI) exhibits anti-fibrinolytic activity by removing C-terminal lysine residues from fibrin or plasminogen receptor proteins on the cellular surface, and plays an important role in the regulation of fibrinolysis. In this study, we examined the regulation of TAFI in hepatocytes during liver regeneration, and revealed its pivotal role in hepatocyte proliferation. In rat models, partial hepatectomy or carbon tetrachloride (CCl4)-induced acute liver injury suppressed the levels of plasma TAFI activity and hepatic TAFI mRNA, whereas this operation markedly increased both the hepatic plasmin activity and the level of proliferating cell nuclear antigen.

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The hepatocyte spheroid formation on the Primariatrade mark dish (PM) occurred as a result of cell migration, adhesion, and shape changes. On the other hand, hepatocytes plated on 1.5% agarose-coated dishes did not attach to the dishes.

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