bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2026–02–01
28 papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. Oligoprotein type I interferon signatures, but not TREX1 variants, increase risk of systemic lupus erythematosus in UK Biobank.
  2. Methylation, acetylation and cell fate.
  3. A hostile environment for a commensal.
  4. Targeting modulated vascular smooth muscle cells in atherosclerosis via FAP-directed immunotherapy.
  5. A step towards building miniature human livers.
  6. Public access's next frontier.
  7. Damage from a heart attack comes from brain signals, mouse study suggests.
  8. Single-cell proteomic landscape of the developing human brain.
  9. Pan-Epigenetic Age Prediction in Mammals.
  10. Wikipedia is needed now more than ever, 25 years on.
  11. Obesity disrupts ILC2 metabolic and functional homeostasis by inhibiting mTORC1 signaling.
  12. CD38 endows local antigen-specific Treg cells with stress resilience for control of compartmentalized CNS inflammation.
  13. A triple-node heart-brain neuroimmune loop underlying myocardial infarction.
  14. Unravelling the molecular mechanisms causal to type 2 diabetes across global populations and disease-relevant tissues.
  15. DNA-protein cross-links promote cGAS-STING-driven premature aging and embryonic lethality.
  16. CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting.
  17. A new blueprint of brain border immunity.
  18. Epidemiological approaches to refine biomarkers of aging.
  19. TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism.
  20. RORγt+ dendritic cells are a distinct lymphoid-derived lineage.
  21. Cycling molecular assemblies for Golgi imaging and disruption.
  22. Communicating Medical Numbers.
  23. In Vivo Chemical Reprogramming Is Associated With a Toxic Accumulation of Lipid Droplets Hindering Rejuvenation.
  24. Ether lipids influence cancer cell fate by modulating iron uptake.
  25. The surprisingly big health benefits of just a little exercise.
  26. Lysosomes as hubs of metabolic sensing and cellular homeostasis.
  27. Identifying genes and proteins with causal effects on type 2 diabetes risk across tissues and populations.
  28. A heterogeneous population code at the first synapse of vision.
  1. Nat Commun. 2026 Jan 27. 17(1): 1073
    Oligoprotein type I interferon signatures, but not TREX1 variants, increase risk of systemic lupus erythematosus in UK Biobank.
    Bastien Rioux, Sarah McGlasson, Deborah Forbes, Katy R Reid, Anna Klingseisen, Joe Berry, Neeraj Dhaun, Wan Fai Ng, William Whiteley, David P J Hunt.
      The 3' - 5' DNA exonuclease, TREX1, is a negative regulator of the type I interferon response, while TREX1 variants are considered to confer risk for non-monogenic systemic lupus erythematosus (SLE). Here we analyse TREX1 sequences in 469,229 UK Biobank participants together with multi-omics data from the UK Biobank Pharma Proteomics Project to reappraise the contribution of reported TREX1 risk variants in SLE. We find that TREX1 variants are not associated with increased risk for SLE in UK Biobank, and most reported risk variants are functionally neutral in mutagenesis experiments. Deriving an oligoprotein interferon signature from broad capture proteomics, we find that this signature is associated with elevated SLE risk, but is not elevated in TREX1 variant carriers. Furthermore, TREX1 variants are not associated with other autoimmune diseases with a prominent oligoprotein interferon signature. Finally, meta-analysis of published studies confirms the lack of support for the association between SLE and TREX1 risk variants. In summary, we find that, while oligoprotein type I interferon signatures increase risk of SLE, TREX1 variants do not.
    DOI:  https://doi.org/10.1038/s41467-025-67832-z
  2. Nat Metab. 2026 Jan 28.
    Methylation, acetylation and cell fate.
    Dan Huang, Ziwei Dai.
      
    DOI:  https://doi.org/10.1038/s42255-025-01449-w
  3. Sci Signal. 2026 Jan 27. 19(922): eaef7044
    A hostile environment for a commensal.
    Wei Wong.
      A high-fat diet impairs the growth of a commensal that produces lipids with anti-obesogenic effects in mice.
    DOI:  https://doi.org/10.1126/scisignal.aef7044
  4. Science. 2026 Jan 29. eadx1736
    Targeting modulated vascular smooth muscle cells in atherosclerosis via FAP-directed immunotherapy.
    Junedh M Amrute, In-Hyuk Jung, Tracy Yamawaki, Wen-Ling Lin, Andrea Bredemeyer, Johanna Diekmann, Sikander Hayat, Xianglong Zhang, Devin L Wakefield, Xin Luo, Sidrah Maryam, Gyu Seong Heo, Steven Yang, Chang Jie Mick Lee, Chen Wang, Caroline Chou, Christoph Kuppe, Kevin D Cook, Atilla Kovacs, Vishnu Chintalgattu, Danielle Pruitt, Jose Barreda, Nathan O Stitziel, Paul Cheng, Yongjian Liu, Rafael Kramann, Daniel Kreisel, Roger S-Y Foo, Ingrid C Rulifson, Scott Martin, David Grunert, Melissa Thomas, Jixin Cui, Thomas Quertermous, Frank M Bengel, Simon Jackson, Chi-Ming Li, Brandon Ason, Kory J Lavine.
      Vascular smooth muscle cell (VSMC) diversification drives atherosclerotic coronary artery disease (CAD). Mechanisms governing these cell state transitions remain unclear. We applied multiomic single-cell profiling, epitope mapping, and spatial transcriptomics across 27 human coronary arteries, identifying fibroblast activation protein (FAP) as a marker of modulated VSMCs. Lineage tracing in mice indicated that FAP+ cells originate from Myh11+ VSMCs, and FAP PET imaging in CAD patients showed plaque uptake. FAP+ cells states resided in the macrophage-rich neo-intima. Therapeutically, we developed an anti-FAP bispecific T-cell engager, which reduced plaque burden and remodeled the stromal-immune microenvironment through T-cell clonal expansion. Our study delivers a single-cell and spatial atlas of human CAD, establishes FAP as a marker of modulated VSMCs, and highlights immunotherapy for lipid-independent targets.
    DOI:  https://doi.org/10.1126/science.adx1736
  5. Nature. 2026 Jan 28.
    A step towards building miniature human livers.
      
    Keywords:  Biotechnology; Medical research
    DOI:  https://doi.org/10.1038/d41586-025-04012-5
  6. Science. 2026 Jan 29. 391(6784): 522-524
    Public access's next frontier.
    Meagan Phelan.
      
    DOI:  https://doi.org/10.1126/science.aef7772
  7. Nature. 2026 Jan 28.
    Damage from a heart attack comes from brain signals, mouse study suggests.
    Miryam Naddaf.
      
    Keywords:  Cardiovascular biology; Immunology; Neuroscience
    DOI:  https://doi.org/10.1038/d41586-026-00261-0
  8. Nat Biotechnol. 2026 Jan 27.
    Single-cell proteomic landscape of the developing human brain.
    Tianzhi Wu, Lihua Jiang, Tanzila Mukhtar, Li Wang, Ruiqi Jian, Cheng Wang, Tiffany Trinh, Arnold R Kriegstein, Michael Snyder, Jingjing Li.
      Profiling protein abundance and dynamics at single-cell resolution in complex human tissues is challenging. Given the discordance between transcript and protein abundance observed in studies of the human cerebral cortex, we developed an optimized workflow that combines label-free single-cell mass spectrometry with precise sample preparation to resolve quantitative proteomes of individual cells from the developing human brain. Our method achieves deep proteomic coverage (~800 proteins per cell) even in small immature prenatal human neurons (diameter ~7-10 μm, ~50 pg protein), capturing major brain cell types and enabling proteome-wide characterization at single-cell resolution. We document extensive transcriptome-proteome discordance across cell types, particularly in genes associated with neurodevelopmental disorders. Proteins exhibit markedly higher cell-type specificity than their mRNA counterparts, underscoring the importance of proteomic-level analysis. By reconstructing developmental trajectories from radial glia to excitatory neurons at the proteomic level, we identify dynamic, stage-specific protein co-expression modules and pinpoint the intermediate progenitor-to-neuron transition as a genetically vulnerable phase associated with autism.
    DOI:  https://doi.org/10.1038/s41587-025-02980-7
  9. Aging Cell. 2026 Feb;25(2): e70380
    Pan-Epigenetic Age Prediction in Mammals.
    Zane Koch, Adam Li, Trey Ideker.
      Epigenetic remodeling is a hallmark of aging, yet which epigenetic layers are most affected during aging-and the extent to which they are interrelated-is not well understood. Here, we perform a comprehensive analysis of epigenetic aging encompassing 6 histone marks and DNA methylation measured across 12 tissues from > 1000 humans and mice. We identify a synchronized pattern of age-related changes across these epigenetic layers, with all changes converging upon a common set of genes. Notably, an epigenetic clock based on these genes can accurately predict age using data from any layer (Spearman ρ: 0.70 in humans, 0.81 in mice). Applying this "pan-epigenetic" clock, we observe that histone modification and DNA methylation profiles agree in the prediction of which individuals are aging more rapidly or slowly. These results demonstrate that epigenetic modifications are subject to coordinated remodeling over the lifespan, offering a unified view of epigenetic aging.
    DOI:  https://doi.org/10.1111/acel.70380
  10. Nature. 2026 Jan;649(8099): 1079-1080
    Wikipedia is needed now more than ever, 25 years on.
      
    Keywords:  Communication; Media; Scientific community; Society
    DOI:  https://doi.org/10.1038/d41586-026-00074-1
  11. Cell Mol Immunol. 2026 Jan 27.
    Obesity disrupts ILC2 metabolic and functional homeostasis by inhibiting mTORC1 signaling.
    Lin Hu, Dongdi Wang, Yue Chen, Jinxin Qiu, Hongdong Wang, Youqin Zhang, Michelle Zhang, Xiaohui Su, Ju Qiu, Jiping Sun, Lei Shen.
      Group 2 innate lymphoid cells (ILC2s) play crucial roles in maintaining adipose tissue homeostasis. Recent studies indicate that ILC2s are dysregulated in obesity. However, the regulatory mechanisms governing adipose tissue ILC2 function remain inadequately explored. In this study, we demonstrated that mechanistic target of rapamycin complex 1 (mTORC1) activity is impaired in adipose tissue ILC2s from obese mice and humans. Deletion of Raptor, a critical adaptor protein in mTORC1, results in reduced numbers of ILC2s and diminished type 2 cytokine production in ILC2s, leading to increased adipose tissue inflammation and insulin resistance. Mechanistically, mTORC1 signaling upregulates PPARγ expression through HIF-1α, which promotes mitochondrial biogenesis and ST2 expression to sustain ILC2 metabolic and functional fitness. Together, our data identify mTORC1 as a crucial regulator that coordinates adipose tissue ILC2 metabolic and immunological homeostasis and prevents obesity-associated insulin resistance.
    Keywords:  Group 2 innate lymphoid cells; PPARγ; ST2; mTORC1
    DOI:  https://doi.org/10.1038/s41423-026-01389-9
  12. Nat Immunol. 2026 Jan 29.
    CD38 endows local antigen-specific Treg cells with stress resilience for control of compartmentalized CNS inflammation.
    Hsin-Hsiang Chen, Sofia Tyystjärvi, Diego Ruiz Navarro, Ravi Kant, Tanja Groll, Ingrid Wagner, Helena Domínguez Moreno, Irene Bonafonte-Pardàs, Rupert Öllinger, Ali Maisam Afzali, Sylvia Heink, Lisa Charlotte Richter, Christopher Sie, Gildas Lepennetier, Lea Seeholzer, Katja Steiger, Doron Merkler, Roland Rad, Gunnar Schotta, Benjamin Schubert, Andreas Muschaweckh, Thomas Korn.
      Foxp3-expressing regulatory T (Treg) cells protect against systemic autoimmunity. However, little is known about the significance of Treg cells in inflammation-experienced tissues. Here, we use an experimental autoimmune encephalomyelitis model and show that Treg cells accumulate and persist in the central nervous system (CNS) long after the resolution of the bulk of the inflammatory infiltrate. CNS-specific depletion of postinflammatory Treg cells, but not systemic depletion of Treg cells, results in autoimmune inflammatory flares in the CNS by residual local effector T cells. Expression of the NAD-consuming ectoenzyme CD38 is crucial for the functional adaptation of postinflammatory CNS Treg cells to a stressful microenvironment, in which access to interleukin-2 (IL-2) is limited. CD38 counteracts ADP-ribosylation of the IL-2 receptor and thus maintains its high sensitivity to IL-2. This fully functional high-affinity IL-2 receptor prevents the loss of tissue-resident antigen-specific Treg cells. These 'stress-tolerant' CNS Treg cells impede the collapse of immune homeostasis in the CNS once acute inflammation is controlled.
    DOI:  https://doi.org/10.1038/s41590-025-02416-z
  13. Cell. 2026 Jan 27. pii: S0092-8674(25)01506-5. [Epub ahead of print]
    A triple-node heart-brain neuroimmune loop underlying myocardial infarction.
    Saurabh Yadav, Van K Ninh, Jonathan W Lovelace, Jingrui Ma, Alexander Pham, Rebecca J Salamon, Enyu Ji, Youngseo Na, Zhenxing Fu, Stephanie I Ugochukwu, Wanning Cui, Ruchi Sehgal, Kevin R King, Vineet Augustine.
      Myocardial infarction (MI) triggers adverse cardiac events, immune responses, and nervous system activation, but the neural and neuroimmune mechanisms remain understudied. Using single-cell RNA sequencing (scRNA-seq) and tissue clearing, we identified transient receptor potential vanilloid-1 (TRPV1)-expressing vagal sensory neurons (VSNs) that increase ventricular innervation post MI. Ablating these VSNs mitigated MI pathology, reducing infarct size, abnormal electrocardiograms, cardiac dysfunction, sympathetic innervation, and pro-inflammatory cytokine interleukin 1β (IL-1β). Single-nuclei RNA-seq (snRNA-seq) and spatial transcriptomics revealed reduced border zone expansion in MI hearts following VSN ablation. Tracing the effects to the brain, we found that MI activated angiotensin II receptor type 1 (AT1aR)-expressing neurons in the paraventricular nucleus (PVN), whose inhibition mirrored benefits of TRPV1 VSN ablation. Additionally, the superior cervical ganglia (SCGs) exhibited intensified post-MI sympathetic innervation and IL-1β signaling. Blocking IL-1β in the SCG significantly reduced complications post MI. This study reveals a triple-node heart-brain loop underlying MI and potential therapeutic targets.
    Keywords:  cardioception; central circuits; heart-brain; hypothalamus; immune system; inflammation; myocardial infarction; peripheral circuits; sympathetic ganglia; vagus nerve
    DOI:  https://doi.org/10.1016/j.cell.2025.12.058
  14. Nat Metab. 2026 Jan 27.
    Unravelling the molecular mechanisms causal to type 2 diabetes across global populations and disease-relevant tissues.
    Ozvan Bocher, Ana Luiza Arruda, Satoshi Yoshiji, Chi Zhao, Alicia Huerta-Chagoya, Chen-Yang Su, Xianyong Yin, Davis Cammann, Henry J Taylor, Jingchun Chen, Ken Suzuki, Ravi Mandla, Ta-Yu Yang, Fumihiko Matsuda, Josep M Mercader, Jason Flannick, James B Meigs, Alexis C Wood, Marijana Vujkovic, Benjamin F Voight, Cassandra N Spracklen, Jerome I Rotter, Andrew P Morris, Eleftheria Zeggini.
      Type 2 diabetes (T2D) is a prevalent disease arising from complex molecular mechanisms. Here we leverage T2D genetic associations to identify causal molecular mechanisms in an ancestry-aware and tissue-aware manner. Using two-sample Mendelian randomization corroborated by colocalization across four global ancestries, we analyse 20,307 gene and 1,630 protein expression levels using blood-derived cis-quantitative trait loci (QTLs). We detect causal effects of genetically predicted levels of 335 genes and 46 proteins on T2D risk, with 16.4% and 50% replication in independent cohorts, respectively. Using gene expression cis-QTLs derived from seven T2D-relevant tissues, we identify causal links between the expression of 676 genes and T2D risk, refining known associations such as BAK1 and describing additional ones like CPXM1. Causal effects are mostly shared across ancestries but are highly heterogeneous across tissues. Our findings provide insights into cross-ancestry and tissue-informed multi-omics causal inference approaches and demonstrate their power in uncovering molecular processes driving T2D.
    DOI:  https://doi.org/10.1038/s42255-025-01444-1
  15. Science. 2026 Jan 29. 391(6784): eadx9445
    DNA-protein cross-links promote cGAS-STING-driven premature aging and embryonic lethality.
    Ines Tomaskovic, Cristian Prieto-Garcia, Maria Boskovic, Mateo Glumac, Tsung-Lin Tsai, Thorsten Mosler, Rubina Kazi, Rajeshwari Rathore, Jorge Andrade, Marina Hoffmann, Giulio Giuliani, Anne-Claire Jacomin, Raquel S Pereira, Elias Knop, Laurens Wachsmuth, Petra Beli, Koraljka Husnjak, Manolis Pasparakis, Andrea Ablasser, Daniela S Krause, Michael Potente, Stamatis Papathanasiou, Janos Terzic, Ivan Dikic.
      DNA-protein cross-links (DPCs) are highly toxic DNA lesions that block replication and transcription, but their impact on organismal physiology is unclear. We identified a role for the metalloprotease SPRTN in preventing DPC-driven immunity and its pathological consequences. Loss of SPRTN activity during replication and mitosis lead to unresolved DNA damage, chromosome segregation errors, micronuclei formation, and cytosolic DNA release that activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. In a Sprtn knock-in mouse model of Ruijs-Aalfs progeria syndrome, chronic cGas-Sting signaling caused embryonic lethality through inflammation and innate immune responses. Surviving mice displayed aging phenotypes beginning in embryogenesis, which persisted into adulthood. Genetic or pharmacological inhibition of cGas-Sting rescued embryonic lethality and alleviated progeroid phenotypes.
    DOI:  https://doi.org/10.1126/science.adx9445
  16. Nat Commun. 2026 Jan 26. 17(1): 101
    CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting.
    Ari Itoh-Nakadai, Minggao Liang, Michiho Shindo, Chen Bibi, Mariko Tomizawa-Murasawa, Saera Fujiki, Akiko Kaneko, Emi Kanamaru, Mari Hashimoto, Hiroshi Kajita, Yoshinari Ando, Miki Kojima, Jonathan Moody, Makoto Iwasaki, Shinsuke Takagi, Ryo Nakagawa, Saumya Agrawal, Hanae Amitani-Iijima, Kaori Sato, Yuriko Sorimachi, Nahoko Suzuki, Takehiro Fukami, Kazuharu Hanada, Satoshi Morita, Kazushige Katsura, Takehisa Matsumoto, Maiko Kobayashi, Masahiko Kato, Yasuyuki Negishi, Mikako Shirouzu, Yuho Najima, Keiyo Takubo, Chung Chau Hon, Naoyuki Uchida, Shuichi Taniguchi, Yukihide Momozawa, Piero Carninci, Leonard D Shultz, Yoriko Saito, Michiel de Hoon, Jay W Shin, Fumihiko Ishikawa.
      Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B-cell malignancies, but its success in acute myeloid leukemia (AML) remains limited. Durable responses depend on the formation of long-lived memory T cells, whereas T cell exhaustion contributes to non-response and relapse. In patients with AML who achieved remission after cord blood transplantation, we here first observe enrichment of memory T cells with high expression of the chemokine receptor CXCR4. Next, we show that engineering CAR-T cells to co-express CXCR4 enhances their persistence and anti-leukemic activity in patient-derived xenograft models. Using single-cell profiling and metabolic analysis, we find that CXCR4 promotes memory-associated transcriptional programs, reduces exhaustion, and supports oxidative metabolism. These effects are observed with CAR-T cells targeting CD25 or CD96 as AML-associated targets. Our results indicate that CXCR4 strengthens CAR-T cell memory and durability, offering a strategy to improve immunotherapy outcomes in AML and beyond.
    DOI:  https://doi.org/10.1038/s41467-025-67745-x
  17. Nat Immunol. 2026 Jan 27.
    A new blueprint of brain border immunity.
    Hannah E Ennerfelt, Katrin I Andreasson.
      
    DOI:  https://doi.org/10.1038/s41590-025-02404-3
  18. Nat Aging. 2026 Jan 29.
    Epidemiological approaches to refine biomarkers of aging.
    Thaís Lopes de Oliveira, Nancy L Pedersen, Joris Deelen, Sara Hägg.
      
    DOI:  https://doi.org/10.1038/s43587-026-01064-8
  19. Nat Commun. 2026 Jan 24.
    TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism.
    Astrid F Feiten, Kilian Dahm, Kai Schlepckow, Bettina van Lengerich, Jung H Suh, Anika Reifschneider, Benedikt Wefers, Laura M Bartos, Karin Wind-Mark, Lis de Weerd, Thomas Ulas, Elena De-Domenico, Pia Grundschöttel, Stefan Paulusch, Benjamin Tast, Tamisa Honda, Stephan A Müller, Matthias Becker, Igor Khalin, Alessio Ricci, Arthur Liesz, Bettina Brunner, Claudia Krenner, Katrin Buschmann, Brigitte Nuscher, Lena Spieth, Niklas Junker, Stefan A Berghoff, Sonnet S Davis, Jonas J Neher, Wolfgang Wurst, Nikolaus Plesnila, Joseph W Lewcock, Mikael Simons, Stefan F Lichtenthaler, Gilbert Di Paolo, Matthias Brendel, Anja Capell, Kathryn M Monroe, Joachim L Schultze, Christian Haass.
      Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer's disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in major immunometabolic pathways, and enrichment of genes in oxidative phosphorylation and cholesterol metabolism in microglia with increased TREM2 expression. Metabolic and lipidomic profiling of sorted microglia showed that, independent of Aβ pathology, TREM2 expression correlated with signatures consistent with increased cellular redox, energetics, and cholesterol homoeostasis. In accordance, metabolic activity correlated with phagocytic capacity. Finally, we performed chronic treatment with a TREM2 agonist antibody and identified a window of TREM2 expression where microglia are most responsive, thereby informing clinical applications of TREM2 agonists.
    DOI:  https://doi.org/10.1038/s41467-026-68706-8
  20. Sci Immunol. 2026 Jan 27. eaed7439
    RORγt+ dendritic cells are a distinct lymphoid-derived lineage.
    Patrick Fernandes Rodrigues, Shitong Wu, Tihana Trsan, Bishan Bhattarai, Santosh K Panda, José Luís Fachi, Marina Cella, Marco Colonna.
      How tolerogenic dendritic cell (DC) lineages are established to prevent inappropriate immune responses to commensals and food antigens remains unclear. We identify RORγt+ DCs in mice as a distinct lymphoid-derived lineage to safeguard intestinal tolerance. Using lineage tracing and single-cell transcriptomics, we unveiled bone marrow-resident Rorc(t)+ progenitors, which include a RORγt+ innate lymphoid progenitor (RILP) that generates both ILC3s and RORγt+ DCs, and a pre-RORγt+ DC precursor committed exclusively to the RORγt+ DC lineage. RORγt+ DC development required the Rorc +7 kb enhancer, whose accessibility was ensured by the repressors REV-ERBα and REV-ERBβ, and depended on the transcription factors PRDM16 and PU.1 for lineage commitment. Loss of any of these regulators abrogated RORγt+ DC differentiation, reduced peripheral regulatory T (Treg) cell induction, and skewed toward T helper 2 responses. Together, these findings define murine RORγt+ DCs as a lymphoid-derived lineage whose enhancer- and transcription factor-driven development is essential for peripheral Treg cell-mediated immune homeostasis.
    DOI:  https://doi.org/10.1126/sciimmunol.aed7439
  21. Nat Commun. 2026 Jan 28.
    Cycling molecular assemblies for Golgi imaging and disruption.
    Weiyi Tan, Qiuxin Zhang, Zhiyu Liu, Kangqiang Qiu, Divyanshu Mahajan, Thomas Gerton, Noah Copperman, Erica C Dresselhaus, Chaoshuang Xia, Cheng Lin, William Lau, Mikki Lee, Isabela Ashton-Rickardt, Pengyu Hong, Daniela Dinulescu, Jer-Tsong Hsieh, Avital A Rodal, David M Loeb, Ronny Drapkin, Jiajie Diao, Lei Lu, Bing Xu.
      The Golgi apparatus is a central hub for protein trafficking and signaling, yet its rapid imaging and cell-selective disruption remain challenging. Here, we report cycling molecular assemblies (CyMA) for fast Golgi imaging and cell-selective interference. CyMA precursors are acetylated amphiphilic thiopeptides that traverse plasma membrane and are deacetylated by intracellular thioesterases. This exposes thiols that undergo palmitoylation by Golgi-resident palmitoyl acyltransferases utilizing palmitoyl-CoA. The resulting palmitoylated peptides self-assemble into dynamic nanostructures (i.e., CyMA) localized at the Golgi. Their continuous, reversible S-acylation enables near-instantaneous Golgi imaging. Replacing fluorophore with a biphenyl motif promotes CyMA accumulation and disrupts functions such as protein modifications, trafficking, and secretion, leading to cell death. This study establishes dynamic supramolecular assembly as an active and selective strategy for Golgi-targeting, pleiotropically interfering with Golgi functions, which may be applicable to targeting other organelles by utilizing alternative enzyme switches to enable kinetic trapping.
    DOI:  https://doi.org/10.1038/s41467-026-68768-8
  22. JAMA. 2026 Jan 26.
    Communicating Medical Numbers.
    Abagail D Cohen, Ambria Williams, Liza-Marie Johnson.
      
    DOI:  https://doi.org/10.1001/jama.2025.23443
  23. Aging Cell. 2026 Feb;25(2): e70390
    In Vivo Chemical Reprogramming Is Associated With a Toxic Accumulation of Lipid Droplets Hindering Rejuvenation.
    Wayne Mitchell, Cecília G de Magalhães, Alexander Tyshkovskiy, Yushi Uchida, Ludger J E Goeminne, Takaharu Ichimura, Emery L Ng, Alibek Moldakozhayev, Joseph V Bonventre, Vadim N Gladyshev.
      Partial reprogramming has emerged as a promising strategy to reset the epigenetic landscape of aged cells towards more youthful profiles. Recent advancements have included the development of chemical reprogramming cocktails that can lower the epigenetic and transcriptomic age of cells and upregulate mitochondrial biogenesis and oxidative phosphorylation. However, the ability of these cocktails to affect biological age in a mammalian aging model has yet to be tested. Here, we have characterized the effects of partial chemical reprogramming on mitochondrial structure and function in aged mouse fibroblasts and tested its in vivo efficacy in genetically diverse male UM-HET3 mice. This approach increases the size of mitochondria, alters cristae morphology, causes an increased fusing of mitochondrial networks, and speeds up movement velocity. At lower doses, the chemical reprogramming cocktail can be safely administered to middle-aged mice using implantable osmotic pumps, albeit with no effect on the transcriptomic age of kidney or liver tissues and only a modest effect on the expression of OXPHOS complexes. However, at higher doses, the cocktail causes a drastic reduction in body weight necessitating euthanasia. In the livers and kidneys of these animals, we observe significant increases in lipid droplet accumulation, as well as changes in mitochondrial morphology in the livers that are associated with mitochondrial stress. Thus, partial chemical reprogramming may induce mitochondrial stress and lead to significant lipid accumulation, which may cause toxicity and hinder the rejuvenation of cells and tissues in aged mammals.
    Keywords:  aging; aging biomarkers; chemical reprogramming; lipid droplets; mitochondria; mitochondrial morphology; oxidative phosphorylation; rejuvenation; reprogramming
    DOI:  https://doi.org/10.1111/acel.70390
  24. Nat Commun. 2026 Jan 27.
    Ether lipids influence cancer cell fate by modulating iron uptake.
    Ryan P Mansell, Sebastian Müller, Jia-Shu Yang, Sarah Innes-Gold, Sunny Das, Ferenc Reinhardt, Kim Janina Sigmund, Vaishnavi V Phadnis, Zhengpeng Wan, Jillian Stark, Daehee Hwang, Fabien Sindikubwabo, Laurène Syx, Nicolas Servant, Elinor Ng Eaton, Julio L Sampaio, George W Bell, Prathapan Thiru, Amartya Viravalli, Amy Deik, Clary B Clish, Paula T Hammond, Roger D Kamm, Adam E Cohen, Ilya Levental, Natalie Boehnke, Victor W Hsu, Kandice R Levental, Raphaël Rodriguez, Robert A Weinberg, Whitney S Henry.
      Cancer cell fate has been widely ascribed to mutational changes within protein-coding genes associated with tumor suppressors and oncogenes. In contrast, the mechanisms through which the biophysical properties of membrane lipids influence cancer cell survival, dedifferentiation and metastasis have received little scrutiny. Here, we report that cancer cells endowed with high metastatic ability and cancer stem cell-like traits employ ether lipids to maintain low membrane tension and high membrane fluidity. Using genetic approaches and lipid reconstitution assays, we show that these ether lipid-regulated biophysical properties permit non-clathrin-mediated iron endocytosis via CD44, resulting in significant increases in intracellular redox-active iron and enhanced ferroptosis susceptibility. Using a combination of in vitro three-dimensional microvascular network systems and in vivo animal models, we show that loss of ether lipids from plasma membranes also strongly attenuates extravasation, metastatic burden and cancer stemness. These findings illuminate a mechanism whereby ether lipids in carcinoma cells serve as key regulators of malignant progression while conferring a unique vulnerability that can be exploited for therapeutic intervention.
    DOI:  https://doi.org/10.1038/s41467-026-68547-5
  25. Nature. 2026 Jan;649(8099): 1092-1094
    The surprisingly big health benefits of just a little exercise.
    Mariana Lenharo.
      
    Keywords:  Epidemiology; Public health
    DOI:  https://doi.org/10.1038/d41586-026-00237-0
  26. Mol Cell. 2026 Jan 28. pii: S1097-2765(26)00031-6. [Epub ahead of print]
    Lysosomes as hubs of metabolic sensing and cellular homeostasis.
    Aakriti Jain, Roberto Zoncu.
      Lysosomes are hubs that couple macromolecular breakdown to cell-wide signaling by sensing metabolic, damage-associated, and environmental cues. Nutrients liberated in the lysosomal lumen as end-products of macromolecular degradation, including amino acids, lipids, and iron, are exported by dedicated transporters for utilization in the cytoplasm. Nutrient transport across the lysosomal membrane is coupled to its sensing by specialized signaling complexes on the cytoplasmic face, which, in response, mediate communication with other organelles and control cell-wide programs for growth, catabolism, and stress response. Lysosomes acquire specialized sensing-signaling features in immune cells, where they shape antigen processing, innate immune signaling, and inflammatory cell death, and in neurons, where they act as sentinels of proteostatic and mitochondrial stress, supporting local translation, organelle quality control, and neuroimmune crosstalk. We highlight recently identified pathways and players that position lysosomes as integrators of nutrient status and organelle health to drive tissue-specific physiology.
    Keywords:  amyloid; autophagy; inflammation; lysosome; mTORC1; metabolites; neurodegeneration; organelle contacts; signaling
    DOI:  https://doi.org/10.1016/j.molcel.2026.01.011
  27. Nat Metab. 2026 Jan 28.
    Identifying genes and proteins with causal effects on type 2 diabetes risk across tissues and populations.
      
    DOI:  https://doi.org/10.1038/s42255-025-01447-y
  28. Nat Commun. 2026 Jan 30.
    A heterogeneous population code at the first synapse of vision.
    Tessa Herzog, Takeshi Yoshimatsu, Jose Moya-Diaz, Ben James, Leon Lagnado, Tom Baden.
      Vision begins when photoreceptors convert fluctuations in light intensity into temporal patterns of glutamate release that drive the retinal network. The input-output relation at this first stage has not been studied in vivo so it is not known how it operates across a photoreceptor population. Using glutamate imaging in zebrafish, we find that individual type 1 cones (PR1; ancestral red cones), which dominate daylight vision in non-avian vertebrates, encode visual stimuli with high reliability and time-precision but routinely vary in sensitivity to luminance, contrast and frequency across the population. Variations in input-output relations are generated by feedback from the horizontal cell network that effectively decorrelate feature representation. A model capturing how zebrafish sample their visual environment indicates that heterogenous cone outputs expand the dynamic range of the retina to improve the coding of natural scenes. Moreover, we find that different kinetic release components are used to encode distinct stimulus features in parallel: sustained release linearly encodes low amplitude light and dark contrasts, but transient release encodes large amplitude dark contrasts. This study reveals an unexpected degree of functional heterogeneity within a population of cones and illustrates how separation of different visual features begins in the first synapse in vision.
    DOI:  https://doi.org/10.1038/s41467-026-68757-x
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