Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells

In response to physiological demand, the pituitary gland generates new hormonesecreting cells from committed progenitor cells throughout life. It remains unclear to what extent pituitary stem cells (PSCs), which uniquely express SOX2, contribute to pituitary growth and renewal. Moreover, neither the signals that drive proliferation nor their sources have been elucidated. We have used genetic approaches in the mouse, showing that the WNT pathway is essential for proliferation of all lineages in the gland. We reveal that SOX2+ stem cells are a key source of WNT ligands. By blocking secretion of WNTs from SOX2+ PSCs in vivo, we demonstrate that proliferation of neighbouring committed progenitor cells declines, demonstrating that progenitor multiplication depends on the paracrine WNT secretion from SOX2+ PSCs. Our results indicate that stem cells can hold additional roles in tissue expansion and homeostasis, acting as paracrine signalling centres to coordinate the proliferation of neighbouring cells

Lrig1-expressing epidermal progenitors require SCD1 to maintain the dermal papilla niche

Niche cells are widely known to regulate stem/progenitor cells in many mammalian tissues. In the hair, dermal papilla niche cells are well accepted to regulate hair stem/progenitor cells. However, how niche cells themselves are maintained is largely unknown. We present evidence implicating hair matrix progenitors and the lipid modifying enzyme, Stearoyl CoA Desaturase 1, in the regulation of the dermal papilla niche during the anagen-catagen transition of the mouse hair cycle. Our data suggest that this takes place via autocrine Wnt signalling and paracrine Hedgehog signalling. To our knowledge, this is the first report demonstrating a potential role for matrix progenitor cells in maintaining the dermal papilla niche.Agency for Science, Technology and Research (A*STAR)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionThis work was supported by Biomedical Research Council (BMRC), Agency for Science, Technology, and Research in Singapore (A*STAR); BMRC-A*STAR-EDB IAF-PP for the Skin Research Institute of Singapore (H17/01/a0/004), and Acne and Sebaceous Gland Program (H17/ H17/01/a0/008), and National Medical Research Council Clinician-Scientist Individual Research Grant MOH-CIRG20nov-0009

Identifying novel strategies for treating human hair loss disorders: Cyclosporine A suppresses the Wnt inhibitor, SFRP1, in the dermal papilla of human scalp hair follicles.

Hair growth disorders often carry a major psychological burden. Therefore, more effective human hair growth-modulatory agents urgently need to be developed. Here, we used the hypertrichosis-inducing immunosuppressant, Cyclosporine A (CsA), as a lead compound to identify new hair growth-promoting molecular targets. Through microarray analysis we identified the Wnt inhibitor, secreted frizzled related protein 1 (SFRP1), as being down-regulated in the dermal papilla (DP) of CsA-treated human scalp hair follicles (HFs) ex vivo. Therefore, we further investigated the function of SFRP1 using a pharmacological approach and found that SFRP1 regulates intrafollicular canonical Wnt/β-catenin activity through inhibition of Wnt ligands in the human hair bulb. Conversely, inhibiting SFRP1 activity through the SFRP1 antagonist, WAY-316606, enhanced hair shaft production, hair shaft keratin expression, and inhibited spontaneous HF regression (catagen) ex vivo. Collectively, these data (a) identify Wnt signalling as a novel, non-immune-inhibitory CsA target; (b) introduce SFRP1 as a physiologically important regulator of canonical β-catenin activity in a human (mini-)organ; and (c) demonstrate WAY-316606 to be a promising new promoter of human hair growth. Since inhibiting SFRP1 only facilitates Wnt signalling through ligands that are already present, this 'ligand-limited' therapeutic strategy for promoting human hair growth may circumvent potential oncological risks associated with chronic Wnt over-activation

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

Background Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo-associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the 'comedo switch'. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG-associated skin disorders. Results In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and insulin/insulin-like growth factor 1 receptors; peroxisome proliferator-activated receptor gamma; aryl hydrocarbon receptor; and the Wnt signalling pathway. Where possible, the cellular and molecular mechanisms by which these regulatory factors control SG biology are indicated, along with considerations as to how they might contribute to acne pathogenesis. Conclusions Future research should seek to establish the relative importance, and causative relationships, of altered sebum production, sebum composition, inflammation and abnormal differentiation of sebaceous progenitors to the process of comedo formation in acne. Such an understanding will allow for therapeutic targeting of regulatory factors that control SG homeostasis, with the aim of treating acne

Adequacy of Nutrient Intake and Malnutrition Risk in Older Adults:Findings from the Diet and Healthy Aging Cohort Study

There is a lack of data on the adequacy of nutrient intake and prevalence of malnutrition risk in Asian populations. The aim was to report on the nutrient intake and prevalence of malnutrition risk in a community sample of older adults in Singapore. Analysis was performed on 738 (n = 206 male, n = 532 male, aged 67.6 ± 6.0 years) adults 60 years and above. Intakes of macro- and micronutrients were evaluated against the Recommended Dietary Allowances (RDAs). Malnutrition risk was assessed using the Nutrition Screening Initiative Determine Your Nutritional Health checklist. It was found that 90.5% older adults exceeded the sugar intake, 68.5% males and 57.1% females exceeded the intake limit for saturated fat, and 33% males had inadequate dietary fiber intake when compared to the RDAs. Inadequate dietary calcium intake was found in 49.5% males and 55.3% females. There were 22.3% of older adults at moderate to high malnutrition risk. Singaporean older adults need to reduce their dietary intakes of sugar and saturated fat and increase their intakes in dietary fiber and calcium. Current findings provide public health awareness on the importance of healthy eating and will facilitate decision making by health promotors to deliver targeted nutrition care programs.</p

Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells

The growth and differentiation of mesenchymal stem cells is controlled by various growth factors, the activities of which can be modulated by heparan sulfates. We have previously underscored the necessity of sulfated glycosaminoglycans for the FGF-2-stimulated differentiation of osteoprogenitor cells. Here we show that exogenous application of heparan sulfate to cultures of primary rat MSCs stimulates their proliferation leading to increased expression of osteogenic markers and enhanced bone nodule formation. FGF-2 can also increase the proliferation and osteogenic differentiation of rMSCs when applied exogenously during their linear growth. However, as opposed to exogenous HS, the continuous use of FGF-2 during in vitro differentiation completely blocked rMSC mineralization. Furthermore, we show that the effects of both FGF-2 and HS are mediated through FGF receptor 1 (FGFR1) and that inhibition of signaling through this receptor arrests cell growth resulting in the cells being unable to reach the critical density necessary to induce differentiation. Interestingly, blocking FGFR1 signaling in post-confluent osteogenic cultures significantly increased calcium deposition. Taken together our data clearly suggests that FGFR1 signaling plays an important role during osteogenic differentiation, firstly by stimulating cell growth that is closely followed by an inhibitory affect once the cells have reached confluence. It also underlines the importance of HS as a co-receptor for the signaling of endogenous FGF-2 and suggests that purified glycosaminoglycans may be attractive alternatives to growth factors for improved ex vivo growth and differentiation of MSCs

Structure and Morphology Control in Thin Films of Conjugated Polymers for an Improved Charge Transport

The morphological and structural features of the conjugated polymer films play an important role in the charge transport and the final performance of organic optoelectronics devices [such as organic thin-film transistor (OTFT) and organic photovoltaic cell (OPV), etc.] in terms of crystallinity, packing of polymer chains and connection between crystal domains. This review will discuss how the conjugated polymer solidify into, for instance, thin-film structures, and how to control the molecular arrangement of such functional polymer architectures by controlling the polymer chain rigidity, polymer solution aggregation, suitable processing procedures, etc. These basic elements in intrinsic properties and processing strategy described here would be helpful to understand the correlation between morphology and charge transport properties and guide the preparation of efficient functional conjugated polymer films correspondingly

Inhibiting SFRP1 activity with WAY-316606 enhances human hair growth, increases K85 protein expression, and inhibits spontaneous catagen ex vivo.

<p><b>(A)</b> Hair shaft elongation of human HFs ex vivo with WAY-316606 treatment (<i>n</i> = 31 HFs Control, 30 HFs WAY-316606; from 3 male patient samples). (<b>B</b>) K85 protein quantification using immunofluorescence after 48 hours of treatment with WAY-316606 (<i>n</i> = 16 HFs control, 14 HFs WAY-316606; from 3 male patient samples). (<b>C</b>) Macroscopic quantification of hair cycle stage on day 6 with WAY-316606 treatment. (<b>D–H</b>) Validation of HF cycle stage with Ki-67/TUNEL analysis (<i>n</i> = 21 HFs control, 20 HFs WAY-316606; from 3 male patient samples) and Masson's-Fontana (<i>n</i> = 17 HFs control, 20 HFs WAY-316606; from 3 male patient samples). <b>(I)</b> Working hypothesis. Data are expressed as mean ± SEM. (A, B, E, G, and H) Two-tailed unpaired <i>t</i> test and (F) Mann-Whitney test. Scale bars, A = 1 mm; B, D, and H = 50 μm. Underlying data can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003705#pbio.2003705.s016" target="_blank">S1 Data</a>. AL, Auber’s line; Axin2, axis inhibition protein 2; CsA, Cyclosporine A; DC, differentiating cell; DP, dermal papilla; DPC, dermal papilla cell; HF, hair follicle; K85, Keratin 85; LEF1, lymphoid enhancer binding factor 1; SFRP1, secreted frizzled related protein 1; TAC, transient amplifying cell; WAY, WAY-316606.</p