Transcriptional programming of CD4 T differentiation in viral infection balances effector- and memory-associated gene expression.

After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8 tissue-resident memory T cells (T), the developmental origins and transcriptional regulation of CD4 T remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4 T in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating T1 and the progressive acquisition of a mature T program.

Id3 expression identifies CD4 memory Th1 cells.

Memory CD4 T cells play a pivotal role in mediating long-term protective immunity, positioning them as an important target in vaccine development. However, multiple functionally distinct helper CD4 T-cell subsets can arise in response to a single invading pathogen, complicating the identification of rare populations of memory precursor cells during the effector phase of infection and memory CD4 T cells following pathogen clearance and the contraction phase of infection. Furthermore, current literature remains unclear regarding whether a single CD4 memory T-cell lineage gives rise to secondary CD4 T helper subsets or if there are unique memory precursor cells within each helper lineage.

GTPBP1 resolves paused ribosomes to maintain neuronal homeostasis.

Ribosome-associated quality control pathways respond to defects in translational elongation to recycle arrested ribosomes and degrade aberrant polypeptides and mRNAs. Loss of a tRNA gene leads to ribosomal pausing that is resolved by the translational GTPase GTPBP2, and in its absence causes neuron death. Here, we show that loss of the homologous protein GTPBP1 during tRNA deficiency in the mouse brain also leads to codon-specific ribosome pausing and neurodegeneration, suggesting that these non-redundant GTPases function in the same pathway to mitigate ribosome pausing.

Origins of CD4 circulating and tissue-resident memory T-cells.

In response to infection, naive CD4 T-cells proliferate and differentiate into several possible effector subsets, including conventional T helper effector cells (T 1, T 2, T 17), T regulatory cells (T ) and T follicular helper cells (T ). Once infection is cleared, a small population of long-lived memory cells remains that mediate immune defenses against reinfection. Memory T lymphocytes have classically been categorized into central memory cell (T ) and effector memory cell (T ) subsets, both of which circulate between blood, secondary lymphoid organs and in some cases non-lymphoid tissues.

Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types.

Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart.