The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.
We examined the relation between insulin resistance, plasma glucose and insulin responses to meals, lipoprotein lipase (LPL) activity, and postprandial lipemia in a population of 37 healthy nondiabetic individuals. Plasma glucose and insulin concentrations were determined at frequent intervals from 8 AM through midnight (breakfast at 8 AM and lunch at noon); resistance to insulin-mediated glucose disposal was determined by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of glucose, insulin, and somatostatin; LPL activity was quantified in postheparin plasma; and postprandial concentrations of triglyceride (TG)-rich lipoproteins were assessed by measuring the TG and retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20 to 400 lipoprotein fractions. Significant simple correlation coefficients were found between various estimates of postprandial lipemia and SSPG (r = .38 to .68), daylong insulin response (r = .37 to .58), daylong glucose response (r = .10 to .39), and LPL activity (r = -.08 to -.58). However, when multiple regression analysis was performed, only SSPG remained independently associated with both postprandial TG and retinyl palmitate concentrations. These data provide evidence that insulin resistance plays an important role in regulating the postprandial concentration of TG-rich lipoproteins, including those of intestinal origin.
Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 post conception weeks 1,2 , yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialised needs of the fetus and newborn. Here, we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. Substantial B-lymphocyte expansion in FBM contrasts with FL at the same gestational age. Haematopoietic progenitors from FL, FBM and cord blood (CB) exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we demonstrate are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B-lymphocyte, erythroid and myeloid development due to cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.