Human skin dermis is composed of the superficial papillary dermis and the reticular dermis in the lower layers, which can easily be distinguished histologically. In vitro analyses of fibroblasts from explant cultures from superficial and lower dermal layers suggest that human skin comprises at least two fibroblast lineages with distinct morphology, expression profiles, and functions. However, while for mouse skin cell surface markers have been identified, allowing the isolation of pure populations of one lineage or the other via FACS, this has not been achieved for human skin fibroblasts. We have now discovered two cell surface markers that discriminate between papillary and reticular fibroblasts. While FAPCD90 cells display increased proliferative potential, express PDPN and NTN1, and cannot be differentiated into adipocytes, FAPCD90 fibroblasts express high levels of ACTA2, MGP, PPARγ, and CD36 and readily undergo adipogenic differentiation, a hallmark of reticular fibroblasts. Flow cytometric analysis of fibroblasts isolated from superficial and lower layers of human dermis showed that FAPCD90 cells are enriched in the papillary dermis. Altogether, functional analysis and expression profiling confirms that FAPCD90 cells represent papillary fibroblasts, whereas FAPCD90 fibroblasts derive from the reticular lineage. Although papillary and reticular fibroblasts are enriched in the upper or lower dermis, respectively, they are not spatially restricted, and the microenvironment seems to affect their function.

T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αβ and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αβγδ T cells displayed little overlap of CDR3 sequences with single-positive αβ T cells. Gene signatures, cytokine profiles and in silico receptor–ligand interaction studies indicate their contribution to early skin development. DP αβγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.

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Energy dissipation through the promotion of brown adipose tissue (BAT) or browning of white adipose tissue has recently evolved as novel promising concept in the fight against metabolic disease. New evidence suggests that hormones can contribute to the thermogenic programming of adipocytes through paracrine or endocrine actions. Recent studies in rodents identified parathyroid hormone (PTH) and PTH-related peptide as mediators of energy wasting in cachexia models due to adipocyte browning. However, the effects of PTH on human adipocyte thermogenesis and metabolic activity are unknown. Here we isolated subcutaneous white adipocyte precursor cells (APCs) from human donors followed by stimulation with recombinant PTH. Our data show that acute and chronic PTH administration in primary in vitro differentiated human subcutaneous adipocytes induces a molecular thermogenic program with increased mitochondrial activity and oxidative respiratory capacity. PTH also enhances hormone sensitive lipase activity and lipolysis in human adipocytes which may contribute to the observed thermogenic effects. In summary, we demonstrate here that PTH is a novel mediator of human adipocyte browning, suggesting a hitherto unknown endocrine axis between the parathyroid gland and adipose tissue in humans.

This study confirms that the DBUN can be reliably visualized over its entire course with HRUS in anatomical specimens and in healthy volunteers. Muscle Nerve 56: 1101-1107, 2017.