Interleukin-10 (IL-10) is a multi-faceted anti-inflammatory cytokine which plays an essential role in immune tolerance. Indeed, deficiency of IL-10 or its receptor results in aberrant immune responses that lead to immunopathology. Graft-versus-host disease (GVHD) is the limiting complication of allogeneic stem cell transplantation (SCT) and results from an imbalance in pathological versus regulatory immune networks. A number of immune cells…
Read More
Short tandem repeats (STRs) and variable number tandem repeats (VNTRs) are among the most mutable regions of our genome but are frequently underascertained in studies of disease and evolution. Using long-read sequence data from apes and humans, we present a sequence-based evolutionary framework for ∼20,000 phased STRs and VNTRs. We identify 1,584 tandem repeats that are specifically expanded in human…
Read More

Immune Predictors of Mortality Following RNA Virus Infection

The authors used a screen of genetically diverse mice infected with RNA viruses in combination with comprehensive pre-infection immunophenotyping to identify baseline immune correlates of protection from mortality to virus infection. They defined distinct T-cell correlates associated with survival following viral challenge. This study underscores the need for a protective immune response to be balanced in order to protect the host not only from uncontrolled virus replication but also from disease associated with robust immunity.
Read More
Multiplex genetic assays can simultaneously test thousands of genetic variants for a property of interest. However, limitations of existing multiplex assay methods in cultured mammalian cells hinder the breadth, speed and scale of these experiments. Here, we describe a series of improvements that greatly enhance the capabilities of a Bxb1 recombinase-based landing pad system for conducting different types of multiplex…
Read More
The authors have conducted the first-ever histological and molecular analyses of the developing human cerebellum, and found that there are many stark differences in developmental patterns between the mouse and human cerebellum. For example, they have identified cerebellar progenitors have never been described in any other vertebrate. The findings underline that human developmental studies are essential to define human biology.
Read More
The authors provide some of the first evidence that large copy-number changes that originated in archaic hominins have played an important role in helping our ancestors adapt to new environments as they spread out across the globe. They showed that these ancient duplications carry duplicated genes that are specific to different human populations and absent in others where ancestral interbreeding did not occur.
Read More
The cytokine IL-2 is a critical regulator of immune homeostasis The authors found that, despite substantially reduced IL-2 sensitivity, regulatory T cells maintained selective IL-2 signaling and prevented immune dysregulation following treatment with PC61, even when CD25hi cells were depleted. These findings demonstrate that even with severely curtailed CD25 function, Treg cells retain their selective access to IL-2 in vivo, and this is sufficient to maintain normal Treg cell function and immune homeostasis
Read More
SF3B1 is the most commonly mutated RNA splicing factor in cancer1,2,3,4, but the mechanisms by which SF3B1 mutations promote malignancy are poorly understood. Here we integrated pan-cancer splicing analyses with a positive-enrichment CRISPR screen to prioritize splicing alterations that promote tumorigenesis. We report that diverse SF3B1 mutations converge on repression of BRD9, which is a core component of the recently described non-canonical BAF chromatin-remodelling…
Read More
The ability to expand hematopoietic stem and progenitor cells (HSPCs) ex vivo is critical to fully realize the potential of HSPC-based therapies. In particular, the application of clinically effective therapies, such as cord blood transplantation, has been impeded because of limited HSPC availability. Here, using 3D culture of human HSPCs in a degradable zwitterionic hydrogel, we achieved substantial expansion of…
Read More
Up to 40% of the human proteome, including human small heat shock proteins (sHSPs) and their clients, exist in flexible, disordered states that have defied efforts to characterize experimentally. The authors applied a combination of NMR spectroscopy, hydrogen-deuterium exchange/mass spectroscopy, and computational modeling to gain unprecedented insight into the disordered regions of HSPB1, a ubiquitously-expressed sHSP known to delay aggregation of proteins, including tau involved in neurodegenerative disease.
Read More