Neurons face a fundamental proteostasis challenge: synapses and axons located far from the soma must rapidly remodel their proteome during activity, stress, and development. While local protein synthesis has long been recognized as essential for meeting these demands, classical models largely focused on ribonucleoprotein granules as autonomous carriers of translationally silent mRNAs, treating membranous organelles as parallel logistics or metabolic systems. Recent work overturns this view, revealing that endosomes, lysosomes, axonal endoplasmic reticulum, mitochondria, and their contact sites actively function as mobile translation platforms. In this review, we propose an RBP-centered framework in which phase-separated condensates physically tether specific mRNA cohorts to organelle surfaces, coupling mRNA transport, translational control, and organelle dynamics into a unified network. By organizing recent discoveries into functional modules—long-range transport, localized translation, and stress buffering—this neuron-focused framework identifies organelle-anchored translation factories as a unifying principle of synaptic proteostasis and a broadly applicable design paradigm for highly polarized cells.Keywords RNA-binding proteins, ribonucleoprotein granules, neuronal local translation, organelle-anchored translation

γδ T cells are a highly heterogeneous T cell lineage with diverse immunological functions; however, the developmental origins underlying this heterogeneity, particularly the existence and physiological relevance of extrathymic pathways, remain incompletely defined. Our previously generated transcriptomic datasets indicate that Stab2 is specifically expressed in the yolk sac but not the aortic endothelial cells. Leveraging this spatially restricted expression pattern, we generated a Stab2-CrexERT2 inducible genetic lineage tracing mouse model and demonstrated its ability to label yolk sac-derived hematopoietic cells in vivo. Importantly, we detected the contribution of the yolk sac endothelial cells labeled at embryonic day 9.5 to a subset of Vγ1 γδ T cells in the adult liver but hardly to any hematopoietic progenitors in the thymus and bone marrow. Single-cell transcriptomic profiling combined with functional evaluation revealed that the Stab2-labeled yolk sac endothelial cell-derived hepatic γδ T cells preferentially enrich IFN-γ-producing γδ T1 cells and overrepresent characteristics associated with tissue homeostasis and repair. Collectively, our findings provide direct in vivo evidence for the existence of a bone marrow hematopoietic stem cell-independent and thymus-independent developmental pathway of liver γδ T cells originating from yolk sac endothelial cells, and suggest that different origins and developmental paths may confer distinct functional properties to γδ T cells.

Spermatogenesis is an intricately regulated epigenetic process, yet the exact chromatin dynamics during human meiosis and their systemic failure in non-obstructive azoospermia remain elusive due to the sparsity of single-cell epigenomic data in previous studies. Here, leveraging a high-quality scATAC-seq approach, we mapped over 810,000 cis-regulatory elements across human spermatogenesis. We uncovered a highly synchronized, wave-like activation of master transcription factor networks that precisely orchestrates meiotic progression. Crucially, we traced the dynamic process of opening and closing of chromatin states at meiotic DNA double-strand break hotspot regions at single-cell resolution, defining a transient epigenetic window where thousands of these predefined regions become specifically accessible. In NOA patients, this delicate architecture collapses, leading to severe spermatogenic arrest predominantly at the zygotene stage. We characterize this pathogenesis as the temporal dephasing and decoupling of the activities of master TFs. Furthermore, aberrantly reduced chromatin accessibility at DSB hotspot regions in NOA is potentially associated with defective DSB formation, accompanied by a two- to three-fold increase in sperm aneuploidy. Finally, we establish a functional paradigm for interpreting male infertility by linking non-coding GWAS variants (e.g., the MHC II locus) and rare point mutations to the disruption of cis-regulatory elements. Together, our findings establish a high-resolution epigenetic framework for human spermatogenesis and provide a mechanistic basis for decoding the etiology and heterogeneity of non-obstructive azoospermia.

The bacterial flagellar motor is a protein nanomachine that rotates the flagellum to facilitate bacterial motility. These motors exhibit structural diversity among species, enabling the transmission of varying torques to flagellar filaments to grant bacteria diverse swimming capabilities. Compared to peritrichous flagellar motors, polar flagellar motors are faster machines that transmit higher torque to drive high-speed motility in liquids and empower swimming in viscous environments. However, structural basis of high-torque transmission of the polar flagellar motors is still unclear. Here we present a cryo-electron microscopy structure of the polar flagellar motor in complex with the hook from Vibrio alginolyticus, comprising 295 subunits from 18 proteins. Compared to the peritrichous flagellar rod, this structure reveals an increased number of inter-subunit interactions in the rod of the polar flagellar motor. Nine phospholipid molecules insert into the interface between the export apparatus and the proximal rod. The LP ring contains more electrostatic charges on the inner surface and has fewer physical contacts with the rod, while the HT ring tightly binds to the outer surface of the LP ring. FlrP, a protein of previously unknown function, is identified as a new component of the polar flagellar motor, and extensively participates in the interactions of 15 FliF peptides of the MS ring with the rod. In contrast to that in the peritrichous flagellum, the hook in the polar flagellum has two different conformational states, L- and R-types. These findings provide unprecedented insights into structural adaptations of the bacterial polar flagellar motors for high-torque transmission.