Thymus development, cell by cell: The human thymus is the organ responsible for the maturation of many types of T cells, which are immune cells that protect us from infection. However, it is not well known how these cells develop with a full immune complement that contains the necessary variation to protect us from a variety of pathogens. By performing single-cell RNA sequencing on more than 250,000 cells, Park et al. examined the changes that occur in the thymus over the course of a human life. They found that development occurs in a coordinated manner among immune cells and with their developmental microenvironment. These data allowed for the creation of models of how T cells with different specific immune functions develop in humans. Science , this issue p. eaay3224

Pediatric and adult kidney tumors differ: Understanding tumor origins and the similarities and differences between organ-specific cancers is important for determining treatment options. Young et al. generated more than 72,000 single-cell transcriptomes from healthy and cancerous human kidneys. From these data, they determined that Wilms tumor, a pediatric kidney cancer, originates from aberrant fetal cells, whereas adult kidney cancers are likely derived from a specific subtype of proximal convoluted tubular cell. Science , this issue p. 594

More than two decades ago, experiments on the antiviral mechanisms of IFNs led to the discovery of JAKs and their downstream effectors, the STAT proteins. This pathway has since become a paradigm for membrane-to-nucleus signaling and explains how a broad range of soluble factors, including cytokines and hormones, mediate their diverse functions. Jak/STAT research has not only impacted basic science, particularly in the context of intercellular communication and cell-extrinsic control of gene expression, it also has become a prototype for transition from bench to bedside, culminating in the development and clinical implementation of pathway-specific therapeutics. This brief review synthesizes our current understanding of Jak/STAT biology while taking stock of the lessons learned and the challenges that lie ahead.

Immune landscape of the human kidney: Single-cell RNA sequencing has begun to shed light on the full cellular diversity of specific organs. However, these studies rarely examine organ-specific immune cells. Stewart et al. sequenced healthy adult and fetal kidney samples at a single-cell level to define the heterogeneity in epithelial, myeloid, and lymphoid cells. From this dataset, they identified zonation of cells, with relevance to disease and the varied perturbations that occur in different tumor settings. This profiling of the human kidney generates a comprehensive census of existing cell populations that will help inform the diagnosis and treatment of kidney-related diseases. Science , this issue p. 1461

Background: The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design. Results: This study assesses the effect of cold storage on fresh healthy spleen, esophagus, and lung from ≥ 5 donors over 72 h. We collect 240,000 high-quality single-cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these 3 organs and will allow cross-organ comparison of cell types. We see little effect of cold ischemic time on cell yield, total number of reads per cell, and other quality control metrics in any of the tissues within the first 24 h. However, we observe a decrease in the proportions of lung T cells at 72 h, higher percentage of mitochondrial reads, and increased contamination by background ambient RNA reads in the 72-h samples in the spleen, which is cell type specific. Conclusions: In conclusion, we present robust protocols for tissue preservation for up to 24 h prior to scRNA-seq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.