Lymphatic vessels are essential for skin fluid homeostasis and immune cell trafficking. Whether the lymphatic vasculature is associated with hair follicle regeneration is, however, unknown. Here, using steady and live imaging approaches in mouse skin, we show that lymphatic vessels distribute to the anterior permanent region of individual hair follicles, starting from development through all cycle stages and interconnecting neighboring follicles at the bulge level, in a stem cell‐dependent manner. Lymphatic vessels further connect hair follicles in triads and dynamically flow across the skin. At the onset of the physiological stem cell activation, or upon pharmacological or genetic induction of hair follicle growth, lymphatic vessels transiently expand their caliber suggesting an increased tissue drainage capacity. Interestingly, the physiological caliber increase is associated with a distinct gene expression correlated with lymphatic vessel reorganization. Using mouse genetics, we show that lymphatic vessel depletion blocks hair follicle growth. Our findings point toward the lymphatic vasculature being important for hair follicle development, cycling, and organization, and define lymphatic vessels as stem cell niche components, coordinating connections at tissue‐level, thus provide insight into their functional contribution to skin regeneration.

In our environment, using HbA(1c) for the diagnosis of pre-diabetes and diabetes could increase the target population for preventive and therapeutic measures. Further cost-effectiveness studies are needed before the widespread diagnostic use of HbA(1c) can be recommended.

Response to Clairotte et al. C lairotte et al. (1) recently reported inDiabetes Care that the oscillometric measurement of the ankle-brachial index (Osc-ABI) has lower diagnostic performance in diagnosing peripheral arterial disease (PAD) in diabetic patients when compared with the Dopplermeasured ankle-brachial pressure index (Dop-ABI).Our group has validated the use of an automatic oscillometer (Omron M-7) for Osc-ABI calculation. We chose this model because the sleeve adapts better to the truncated cone morphology of the leg. We used the Doppler Hadeco Bidop (Koven Technology, St. Louis, MO) to measure the sonorous and graphical signal. For the Osc-ABI calculation, three measurements were made and the greatest of these three was chosen as the valid measurement. We studied 228 consecutive patients with arterial hypertension (62.75 Ϯ 12.3 years [mean age Ϯ SD], 51.1% men) of which 69 patients (30.3%) presented with type 2 diabetes.As with the study carried out by Clairotte et al., we achieved good applicability with the Osc-ABI, which was obtainable in 96.2% of the patients. Also in agreement with the results by Clairotte et al., the oscillometer method tended to overestimate the systolic arterial pressure values; hence, the cutoff point to define a pathological ABI would have to be increased from 0.9 to 1.However, in contrast to Clairotte et al., we found a better correlation (Pearson test) between the Osc-ABI and the Dop-ABI both in the total population (r ϭ 0.86) (P Ͻ 0.001) as well as in the diabetic subpopulation (r ϭ 0.88) (P Ͻ 0.001) without significant differences between these groups. The interclass correlation coefficient (inter-observant K) in our population was 0.94 (0.96 in the left leg and 0.94 in the right leg).This discrepancy can be due to the fact that we considered pathological Osc-ABI in those case subjects (17 total case subjects: 8 in the right leg and 9 in the left leg) in which the oscillometer displayed error, unlike Clairotte et al. (1) and other researchers (2-3) who considered these results as invalid.In all these 17 case subjects, the Dop-ABI was Ͻ0.6 and the magnetic resonance angiography confirmed the presence of significant arterial stenosis (Ͼ50%) in the inferior members, supporting the idea that the repeated errors of measurement with the Osc-ABI point to the presence of PAD.It is well known that diabetic patients have greater arterial rigidity (4), which in turn can lead to measurement errors when using the oscillometer method since it is not possible to reach an adequate arterial compression. Therefore, it is probable that Clairotte et al. (1) have underestimated the correlation between the Dop-ABI and the Osc-ABI (5) in their study.In conclusion, we support the use of the oscillometer method for ABI screening equally in both diabetic and nondiabetic populations. The difficulties in obtaining pressure measurements in legs with the oscillometer, especially in diabetic subjects, should not be interpreted as error in the technique but instead as an indication of the presence of ...

Lymphatic vessels (LV) are essential for skin fluid homeostasis and immune cell trafficking, but whether LV are associated with hair follicle (HF) regeneration is not known. Here, by using steady and live imaging approaches in mouse skin, we show that lymphatic capillaries distribute to the anterior permanent region of individual HF and interconnect neighboring HF at the level of the HF bulge, in a hair follicle stem cell (HFSC)-dependent manner. LV further connect individual HF in triads and dynamically flow across the skin. Interestingly, at the onset of the physiological HFSC activation, or upon pharmacological or genetic induction of HF growth, LV transiently expand their caliber suggesting an increased tissue drainage capacity. Interestingly, the physiological LV caliber increase is associated with a distinct gene expression correlated to ECM and cytoskeletal reorganization. Using mouse genetics, we show that the depletion of LV blocks the pharmacological induction of HF growth. Our findings define LV as components of the HFSC niche, coordinating HF connections at tissuelevel, and provide insight into their functional contribution to HF regeneration. Keywords: bulge/ lymphatic endothelial cells/ lymphatic vessels/ hair cycle/ hair follicle/ skin/ stem cells

This short insight covers some of the recent topics relevant to the field of cadherin–catenin adhesion in mediating connections between different cell types, so-called heterotypic or heterocellular connections, in both homeostasis and cancer. These scientific discoveries are increasing our understanding of how multiple cells residing in complex tissues can be instructed by cadherin adhesion receptors to regulate tissue architecture and function and how these cadherin-mediated heterocellular connections spur tumor growth and the acquisition of malignant characteristics in tumor cells. Overall, the findings that have emerged over the past few years are elucidating the complexity of the functional roles of the cadherin–catenin complexes. Future exciting research lies ahead in order to understand the physical basis of these heterotypic interactions and their influence on the behavior of heterogeneous cellular populations as well as their roles in mediating phenotypic and genetic changes as cells evolve through complex environments during morphogenesis and cancer.