Galactose in human metabolism, glycosylation and congenital metabolic diseases: Time for a closer look.

Galactose is an essential carbohydrate for cellular metabolism, as it contributes to energy production and storage in several human tissues while also being a precursor for glycosylation. Galactosylated glycoconjugates, such as glycoproteins, keratan sulfate-containing proteoglycans and glycolipids, exert a plethora of biological functions, including structural support, cellular adhesion, intracellular signaling and many more. The biological relevance of galactose is further entailed by the number of pathogenic conditions consequent to defects in galactosylation and galactose homeostasis. The growing number of rare congenital disorders involving galactose along with its recent therapeutical applications are drawing increasing attention to galactose metabolism. In this review, we aim to draw a comprehensive overview of the biological functions of galactose in human cells, including its metabolism and its role in glycosylation, and to provide a systematic description of all known congenital metabolic disorders resulting from alterations of its homeostasis.

Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells.

Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mechanisms that control this process are poorly understood. Here we report on a droplet-based microfluidic platform to investigate type I IFN production in human pDCs at the single-cell level. We show that type I IFN but not TNFα production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. Combining single-cell cytokine analysis with single-cell RNA-seq profiling reveals no evidence for a pre-existing subset of type I IFN-producing pDCs. By modulating the droplet microenvironment, we demonstrate that vigorous pDC population responses are driven by a type I IFN amplification loop. Our study highlights the significance of stochastic gene regulation and suggests strategies to dissect the characteristics of immune responses at the single-cell level.