The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against ...external stresses and mediating the sensation of touch and pain
. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met
. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.
Functional mechanoelectrical transduction (MET) channels of cochlear hair cells require the presence of transmembrane channel-like protein isoforms TMC1 or TMC2. We show that TMCs are required for ...normal stereociliary bundle development and distinctively influence channel properties. TMC1-dependent channels have larger single-channel conductance and in outer hair cells (OHCs) support a tonotopic apex-to-base conductance gradient. Each MET channel complex exhibits multiple conductance states in ~50 pS increments, basal MET channels having more large-conductance levels. Using mice expressing fluorescently tagged TMCs, we show a three-fold increase in number of TMC1 molecules per stereocilium tip from cochlear apex to base, mirroring the channel conductance gradient in OHCs. Single-molecule photobleaching indicates the number of TMC1 molecules per MET complex changes from ~8 at the apex to ~20 at base. The results suggest there are varying numbers of channels per MET complex, each requiring multiple TMC1 molecules, and together operating in a coordinated or cooperative manner.
Uncombable hair syndrome (UHS), also known as “spun glass hair syndrome,” “pili trianguli et canaliculi,” or “cheveux incoiffables” is a rare anomaly of the hair shaft that occurs in children and ...improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as -recessive inheritance have been reported. However, none of these case subjects were linked to a molecular genetic cause. Here, we report the identification of UHS-causative mutations located in the three genes PADI3 (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin) in a total of 11 children. All of these individuals carry homozygous or compound heterozygous mutations in one of these three genes, indicating an autosomal-recessive inheritance pattern in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wild-type proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic causes of UHS and shed light on its pathophysiology and hair physiology in general.
Mammalian hearing requires the development of the organ of Corti, a sensory epithelium comprising unique cell types. The limited number of each of these cell types, combined with their close ...proximity, has prevented characterization of individual cell types and/or their developmental progression. To examine cochlear development more closely, we transcriptionally profile approximately 30,000 isolated mouse cochlear cells collected at four developmental time points. Here we report on the analysis of those cells including the identification of both known and unknown cell types. Trajectory analysis for OHCs indicates four phases of gene expression while fate mapping of progenitor cells suggests that OHCs and their surrounding supporting cells arise from a distinct (lateral) progenitor pool. Tgfβr1 is identified as being expressed in lateral progenitor cells and a Tgfβr1 antagonist inhibits OHC development. These results provide insights regarding cochlear development and demonstrate the potential value and application of this data set.
The functional aspect of scalp hair is not only to protect from solar radiation and heat/cold exposure but also to contribute to one's appearance and personality. Progressive hair loss has a cosmetic ...and social impact. Hair undergoes three stages of hair cycle: the anagen, catagen, and telogen phases. Through cyclical loss and new-hair growth, the number of hairs remains relatively constant. A variety of factors, such as hormones, nutritional status, and exposure to radiations, environmental toxicants, and medications, may affect hair growth. Androgens are the most important of these factors that cause androgenic alopecia. Other forms of hair loss include immunogenic hair loss, that is, alopecia areata. Although a number of therapies, such as finasteride and minoxidil, are approved medications, and a few others (e.g., tofacitinib) are in progress, a wide variety of structurally diverse classes of phytochemicals, including those present in ginseng, have demonstrated hair growth-promoting effects in a large number of preclinical studies. The purpose of this review is to focus on the potential of ginseng and its metabolites on the prevention of hair loss and its underlying mechanisms.
Objectives
To investigate the characteristics of hairs in Female pattern hair loss (FPHL) patients and healthy females in Southern China.
Materials and methods
Three fundamental hair parameters in ...different scalp areas of 90 Southern Chinese FPHL patients and 83 healthy controls were analyzed by phototrichogram.
Results
Female pattern hair loss patients showed reduced hair density, hair diameter, and terminal/vellus hair ratio. The reduction correlated with the severity of Ludwig staging. Midscalp was the most affected area in FPHL, but occipital and temporal sites were also involved. In normal women, the highest hair density was observed in midscalp, followed by occipital and temporal areas. Peak hair density at midscalp sites was reached at 20s group, then declined with age. Maximum hair diameter at midscalp and occipital sites occurred in 40s group. Terminal/vellus hair ratio tended to increase with age and peak on 50‐60s group.
Conclusion
Reduced hair density and hair diameter, and miniaturization of hair follicles are the characteristics of FPHL in Southern Chinese women. Occipital and temporal sites are also affected in FPHL. Age‐associated changes might have an influence on the hair condition. The values of hair parameters obtained in this study will help to establish reference data for better evaluation of hair disorders.
The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair ...follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (β-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).
Plucked Herzig, Rebecca M
01/2015, Volume:
8
eBook
From the clamshell razors and homemade lye depilatories used in colonial America to the diode lasers and prescription pharmaceuticals available today, Americans have used a staggering array of tools ...to remove hair deemed unsightly, unnatural, or excessive. This is true especially for women and girls; conservative estimates indicate that 99% of American women have tried hair removal, and at least 85% regularly remove hair from their faces, armpits, legs, and bikini lines. How and when does hair become a problem-what makes some growth "excessive"? Who or what separates the necessary from the superfluous?
InPlucked, historian Rebecca Herzig addresses these questions about hair removal. She shows how, over time, dominant American beliefs about visible hair changed: where once elective hair removal was considered a "mutilation" practiced primarily by "savage" men, by the turn of the twentieth century, hair-free faces and limbs were expected for women. Visible hair growth-particularly on young, white women-came to be perceived as a sign of political extremism, sexual deviance, or mental illness. By the turn of the twenty-first century, more and more Americans were waxing, threading, shaving, or lasering themselves smooth. Herzig's extraordinary account also reveals some of the collateral damages of the intensifying pursuit of hair-free skin. Moving beyond the experiences of particular patients or clients, Herzig describes the surprising histories of race, science, industry, and medicine behind today's hair-removing tools.Pluckedis an unsettling, gripping, and original tale of the lengths to which Americans will go to remove hair.
PDF
