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. Other factors that may affect epidermal turnover include ultraviolet damage and genetic factors. These genetic factors are of particular interest as little is known. Although recent skin-focused genome-wide association studies (GWAS) have been conducted, the genetic regions associated with epidermal turnover are almost uninvestigated. Therefore, we conducted a GWAS on epidermal turnover in the Japanese population, using the corneocyte area, which correlates to the rate of epidermal turnover, as an indicator. As a result, rs2278431 (p = 1.29 × 10
) in 19q13.2 was associated with corneocyte size. Furthermore, eQTL analysis suggested that rs2278431 was related to the SPINT2 gene. In addition, SPINT2 knockdown studies using epidermal keratinocytes revealed that SPINT2 is involved in keratinocyte proliferation and in corneocyte size regulation in reconstructed epidermis. These results suggest that rs2278431 is involved in the expression of SPINT2 and affects epidermal turnover.
Wrinkles and sagging are caused by various factors, such as ultraviolet rays; however, recent findings demonstrated that some individuals are genetically predisposed to these phenotypes of skin ...aging. The contribution of single nucleotide polymorphisms (SNPs) to the development of wrinkles and sagging has been demonstrated in genome‐wide association studies (GWAS). However, these findings were mainly obtained from European and Chinese populations. Limited information is currently available on the involvement of SNPs in the development of wrinkles and sagging in a Japanese population. Therefore, we herein performed GWAS on wrinkles at the outer corners of the eyes and nasolabial folds in 1041 Japanese women. The results obtained revealed that 5 SNPs (19p13.2: rs2303098 (p = 3.39 × 10−8), rs56391955 (p = 3.39 × 10−8), rs67560822 (p = 3.50 × 10−8), rs889126 (p = 3.78 × 10−8), rs57490083 (p = 3.99 × 10−8)) located within the COL5A3 gene associated with wrinkles at the outer corners of the eyes. Regarding nasolabial folds, 8q24.11 (rs4876369; p = 1.05 × 10−7, rs6980503; p = 1.25 × 10−7, rs61027543; p = 1.25 × 10−7, rs16889363; p = 1.38 × 10−7) was suggested to be associated with RAD21 gene expression. These SNPs have not been reported in other populations, and were first found in Japanese women population. These SNPs may be used as markers to examine the genetic predisposition of individuals to wrinkles and sagging.
In this study, we conducted GWAS focusing on wrinkles and sagging to clarify the genetic predisposition to aging phenomena in Japanese women, and found new SNPs and genetic regions associated with wrinkles at the outer corners of the eyes and nasolabial folds.
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. Several thousands of copies of mtDNA are considered to be present in a cell, and variants that have occurred in mtDNA are expected to markedly affect the intracellular energy production system and ROS (reactive oxygen species) kinetics. Therefore, recently, mtSNPs have come to be considered very important as a determinant of the individual constitution such as the life‐span and disease susceptibility. In this study, we searched for mtSNPs that affect the individual corneocyte size using samples from 358 Japanese women. As a result, mtSNPs 10609C and 12406A were found to be significantly related to the corneocyte size in the outermost layer of the epidermis. There have been a large number of reports concerning the association between mtSNPs and individual constitution, but little evaluation of their relationships with epidermal properties has been made. The results of the present study first suggested that mtSNPs may affect the epidermal properties in Japanese women.
In this study, we searched for mtSNPs that affect the individual corneocyte size using samples from 358 Japanese women. As a result, mtSNPs 10609C and 12406A were found to be significantly related to the corneocyte size in the outermost layer of the epidermis.
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. However, these studies have mainly focused on the Caucasian population, and only a few association analyses with the constitution and skin type of individuals involving a Japanese population have been conducted. In this study, we conducted a GWAS analysis of 9 phenotypes regarding the constitution or skin type of 1108 Japanese women based on a questionnaire. As a result, in addition to SNPs known to be involved in phenotypes in the past, we discovered new SNPs and genetic regions related to darkness of pigmented spots, skin flushing, frequency of rough skin and responsiveness to cosmetics.
In this study, we conducted a GWAS analysis of 9 phenotypes for the constitution or skin type of Japanese women, and found new SNPs and gene regions associated with the darkness of pigment spots, skin flushing, frequency of rough skin and responsiveness to cosmetics.
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. In this study, skin derived cells were isolated from the epidermis, dermis, and adipose tissue collected from single donor, and immortalization was induced through gene transfer. Subsequently, cell lines that could be used as stem cell models were selected using the differentiation potential and the expression of stem cell markers as indices, and it was confirmed that these could be stably cultured. The immortalized cell lines established in this study have the potential to be applied not only to basic dermatological research but also to a wide range of fields such as drug screening and cell engineering.
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. In general, stem cells are known to require regulatory factors in the pericellular microenvironment, termed the stem cell niche, to maintain their cell function. In this study, we focused on the extracellular matrix proteoglycan decorin (DCN) as a candidate factor for maintaining the human HFSC niche. Gene expression analysis showed that DCN was highly expressed in the bulge region. We observed decreases in DCN expression as well as the number of KRT15‐positive HFSC with age. In vitro experiments with human plucked hair‐derived HFSC revealed that HFSC lost their undifferentiated state with increasing passages, and prior to this change a decrease in DCN expression was observed. Furthermore, knockdown of DCN promoted HFSC differentiation. In contrast, when HFSC were cultured on DCN‐coated plates, they showed an even more undifferentiated state. From these results, as a novel mechanism for maintaining HFSC, it was suggested that DCN functions as a stem cell niche component, and that the deficit of HFSC maintenance caused by a reduction in DCN expression could be a cause of age‐related hair loss.
Background
Stress may have various effects on our bodies. In particular, the skin may be readily influenced by stress. In addition, there are individual differences in the way we feel stress, ...suggesting the involvement of genetic factors in such individual differences.
Objectives
In this study, we analysed the influence of stress on skin condition and ageing involving Japanese females, and investigated single nucleotide polymorphisms (SNPs) that influence perceived stress of an individual.
Methods
We collected genotype data from 1200 Japanese females. At the same time, a questionnaire was conducted on the degree of stress that each subject feels on a daily basis and the current skin condition. We analysed the effects of stress on skin condition and searched for SNPs related to individual stress susceptibility by genome‐wide association studies.
Results
Our data suggested that stress influences skin condition and ageing, as previously reported. And, we found rs74548608 as a SNP that affects perceived stress of an individual. This SNP is located on the upstream of Patched‐1, which is a gene that functions as a sonic hedgehog receptor.
Conclusions
Our study has identified new genetic factors for perceived stress of an individual in the Japanese female. The SNP found in this study may be a candidate factor important for understanding the perceived stress of an individual of Japanese.
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. Previously, we found Gremlin 2 (GREM2) as a novel SASP factor in the skin and reported that GREM2 suppressed the differentiation of adipose-derived stromal/stem cells. In the present study, we investigated the effects of GREM2 on stem cells in the epidermis and dermis.
To examine whether GREM2 expression and the differentiation levels in the epidermis and dermis are correlated, the expressions of GREM2, stem cell markers, an epidermal differentiation marker Keratin 10 (KRT10) and a dermal differentiation marker type 3 procollagen were examined in the skin samples (n = 14) randomly chosen from the elderly where GREM2 expression level is high and the individual differences of its expression are prominent. Next, to test whether GREM2 affects the differentiation of skin stem cells, cells from two established lines (an epidermal and a dermal stem/progenitor cell model) were cultured and induced to differentiate, and recombinant GREM2 protein was added.
In the human skin, the expression levels of GREM2 varied among individuals both in the epidermis and dermis. The expression level of GREM2 was not correlated with the number of stem cells, but negatively correlated with those of both an epidermal and a dermal differentiation markers. The expression levels of epidermal differentiation markers were significantly suppressed by the addition of GREM2 in the three-dimensional (3D) epidermis generated with an epidermal stem/progenitor cell model. In addition, by differentiation induction, the expressions of dermal differentiation markers were induced in cells from a dermal stem/progenitor cell model, and the addition of GREM2 significantly suppressed the expressions of the dermal differentiation markers.
GREM2 expression level did not affect the numbers of stem cells in the epidermis and dermis but affects the differentiation and maturation levels of the tissues, and GREM2 suppressed the differentiation of stem/progenitor cells in vitro. These findings suggest that GREM2 may contribute to the age-related reduction in the capacity to maintain skin homeostasis by suppressing the differentiation of epidermal and dermal stem/progenitor cells.
•In epidermis, the expression levels of GREM2 and KRT10 were negative correlation.•In dermis, the expression levels of GREM2 and Pro-COL3 were negative correlation.•GREM2 suppressed epidermal stem/progenitor cell differentiation in vitro.•GREM2 suppressed dermal stem/progenitor cell differentiation in vitro.
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