- Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre–B ALL
Schjerven et al. compare mouse and human models of pre–B ALL to define conserved target genes and pathways of the tumor suppressor Ikaros, revealing CTNND1 and the early hematopoietic cell-surface receptors SPN (CD43) and CD34 as novel Ikaros targets that each confer oncogenic growth advantage.
- Neuronal CTGF/CCN2 negatively regulates myelination in a mouse model of tuberous sclerosis complex
One of the brain manifestations of tuberous sclerosis complex (TSC) is reduced myelination, but the underlying mechanism remains unclear. Ercan et al. demonstrate that mutant neurons overexpress a protein, connective tissue growth factor (CTGF), which impairs oligodendrocyte maturation and myelination.
- The Eph-related tyrosine kinase ligand Ephrin-B1 marks germinal center and memory precursor B cells
Laidlaw et al. show that Ephrin-B1 is a specific marker of mature germinal center (GC) B cells. Use of Ephrin-B1 allows for the identification of phenotypically distinct GC B cell subsets, including a population that may represent memory precursor B cells.
- Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Öhlund et al. develop a three-dimensional co-culture platform of neoplastic pancreatic ductal organoids and pancreatic stellate cells (PSCs) to characterize the dynamic crosstalk between cancer cells and stromal cells, and to address stromal heterogeneity. The co-cultures reveal the co-existence of two phenotypically distinct populations of PSCs, providing insights into PDA biology and prompting a reconsideration of interventional strategies.
- RAG1/2 induces genomic insertions by mobilizing DNA into RAG1/2-independent breaks
Rommel et al. reveal a novel RAG1/2-mediated insertion pathway, which has the potential to destabilize the lymphocyte genome and shares features with DNA insertions observed in human cancer.
- Soluble TREM2 induces inflammatory responses and enhances microglial survival
Zhong et al. describe two novel roles for soluble TREM2 (sTREM2) in regulation of proinflammatory responses and prevention of cellular apoptosis in microglia.
- Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection
Using a novel human organ donor tissue resource, Gordon et al. reveal how CMV-specific T cells are distributed and function in multiple sites in the context of viral persistence, revealing new insights into immune control of CMV in the body.
- Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity
Levine et al. investigate the extent to which regulatory T cells with either a monoclonal T cell receptor (TCR) or random TCR repertoire in place of their developmentally selected specificities maintain TCR-dependent gene expression and immunosuppressive function.
- A myeloid tumor suppressor role for NOL3
Stanley et al. show that loss of Nol3 in mice leads to a myeloproliferative phenotype resembling primary myelofibrosis, with activation of JAK–STAT signaling and significant cellular and molecular resemblance to human disease. These findings provide a novel role for Nol3 in hematopoiesis and myeloid malignancies.
- EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay
Volpi et al. demonstrate that hypomorphic EXTL3 mutations cause abnormalities of heparan sulfate composition, affect signaling in response to growth factors and cytokines, and perturb thymopoiesis, resulting in a novel genetic disease associating skeletal dysplasia, T cell immunodeficiency, and neurodevelopmental delay.