bims-migras 2026-06-07 papers

Issue of 2026–06–07
three papers selected by
Cliff Dominy

Nat Commun. 2026 Jun 04.

GPI‑anchored protein nanoclusters license migrasome expansion and serve as exocytic platforms for migrasome.

Xiaopeng Li, Ying Li, Renxiang Xie, Haifeng Jiao, Li Yu.

Migrasomes are dynamic organelles that form on migrating cells and mediate intercellular communication through secretory cargo release. Expansion of migrasomes has classically been attributed to tetraspanin-enriched microdomains (TEMs). Here we show that nanoclusters of glycosylphosphatidylinositol-anchored proteins (GPI-APs) act upstream to license expansion, while TEMs provide the stabilizing scaffold. We find that GPI-AP biosynthesis is important for migrasome formation, and that insertion of the GPI anchor alone is sufficient to drive precursor expansion, producing unstable migrasomes that retract. Stimulated emission depletion (STED) microscopy resolves a meshwork of GPI-AP nanoclusters interlocked with, yet largely segregated from, tetraspanin domains in stable migrasomes. Exocytic machinery localizes to GPI-AP regions, where secretion occurs. In cells that naturally generate unstable migrasomes, elevated tetraspanin levels convert them into stable vesicles. We propose a two-module architecture generating unstable, secretion-specialized migrasomes in some cells and stable migrasomes as extracellular extensions of the secretory pathway in others.

DOI: https://doi.org/10.1038/s41467-026-73674-0

Brief Funct Genomics. 2026 Jan 09. pii: elag002. [Epub ahead of print]25

Whole-transcriptome sequencing reveals hypoxic esophageal squamous cell carcinoma-derived migrasomes driving cancer-associated fibroblast activation.

Guan'en Qiao, Zhongping Wang, Meng Wang, Le Feng, Zixuan You, Bing Meng, Kui Dong, Yanping Cao, Pan Li, Junhai Wang, Xinqing Lu, Chunfang Xu.

Cancer-associated fibroblasts (CAFs) activated by intercellular communication contribute to the progression of esophageal squamous cell carcinoma (ESCC). Migrasomes represent a novel mode of intercellular communication. However, the characteristics of ESCC-derived migrasomes in tumor hypoxic microenvironments and their effects on CAFs remain unclear. Migrasomes were isolated from ESCC cells under normoxia/hypoxia, with TSPAN4-GFP labeling, transmission electron microscopy, nanoparticle tracking analysis, and western blot for validation. Whole-transcriptome sequencing analyzed hypoxic migrasome RNA profiles, and ceRNA networks were predicted via RNAhybrid and Miranda. The effect of migrasomes on CAFs was assessed using fluorescence tracing, reverse transcription‑quantitative polymerase chain reaction, Transwell migration, enzyme‑linked immunosorbent assay, and western blot. ESCC cells produced migrasomes. Although hypoxia did not alter their quantity or structure, it significantly altered their RNA cargo, changing the composition of mRNA, lncRNA, and circRNA. Differentially expressed mRNAs were enriched in "Response to hypoxia" and "HIF-1 signaling pathway." DElncRNAs were enriched in "Golgi to plasma membrane protein transport" and "Cell adhesion molecules pathway," while DEcircRNAs were enriched in "ubiquitin binding" and "chromatin remodeling." Predicted ceRNA networks were constructed using RNAhybrid and Miranda, involving 659 miRNAs, 24 lncRNAs, and 132 mRNAs. Fibroblasts internalized migrasomes and acquired a CAF-like phenotype, showing enhanced migration, elevated secretion of IL-1β/TGF-β, and increased CAF marker expression (α-SMA, COL1A1, COL3A1, FAP, PDGFRβ), with effects most pronounced under hypoxic migrasome treatment. This study characterized hypoxic migrasome whole transcriptome landscapes and suggested that hypoxic migrasomes may promote CAF-like changes in vitro, uncovering a novel ESCC-tumor microenvironment interaction mechanism and offering new perspectives for ESCC research.

Keywords: CAF activation; esophageal squamous cell carcinoma; hypoxia; migrasomes; whole-transcriptome sequencing

DOI: https://doi.org/10.1093/bfgp/elag002

J Nanobiotechnology. 2026 Jun 04.

M2 microglia-derived migrasome-enriched extracellular vesicles restore mitochondrial homeostasis to orchestrate neurovascular unit recovery after ischemic stroke.

Yuanjia Zhang, Jie Wu, Leyi Liu, Yiqian Zhu, Jierui Zhang, Jinghong Xu, Xuefeng Shi, Yu Yu, Chao Wang, Jiajing Xiao, Xuanchenye Zhang, Zhaorong Li, Wenqi Huang, Wenzhi Li, Zhongxing Wang, Tingting Li.

Ischemic stroke is a major cause of disability with few treatment options available. Microglia-driven neuroinflammation contributes significantly to stroke pathology, and promoting anti-inflammatory microglial phenotypes represents a promising strategy. Migrasomes are newly discovered organelles mediating intercellular communication, yet their role in ischemic stroke remains unexplored. This study demonstrates that M2 microglia-derived migrasome-enriched extracellular vesicles (EVs) exert potent neuroprotection in both OGD/R cell models and MCAO mice. These migrasome-enriched EVs were efficiently internalized by microglia, astrocytes, neurons, and microvascular endothelial cells, promoting microglial M2 polarization, suppressing astrocytic aberrant activation, reducing neuronal apoptosis, and enhancing angiogenesis. Intracerebral administration of M2 microglia-derived migrasome-enriched EVs significantly reduced infarct volume, ameliorated cerebral edema, improved cerebral blood flow, and accelerated neurological and cognitive recovery without detectable toxicity. Mechanistically, migrasome-enriched EVs activated the cAMP/EPAC1/Rap1 signaling pathway in microglia, leading to restored mitochondrial homeostasis. Collectively, these findings identify M2 microglia-derived migrasome-enriched EVs as novel intercellular messengers that orchestrate neurovascular unit recovery after ischemic stroke, positioning migrasome-enriched EVs as promising candidates for stroke therapy.

Keywords: Ischemic stroke; Microglia polarization; Migrasome-enriched extracellular vesicles; Mitochondrial homeostasis; Neurovascular unit recovery

DOI: https://doi.org/10.1186/s12951-026-04643-4