Translatomics for aging, chronic pain, and stem cell identity
Recent Publications Harnessing the Power of Translatomics
Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.
In this week’s Sunday papers,
- Duré et al. show that epidermal aging involves stem cell–specific translational rewiring that reshapes identity and regenerative capacity.
- Siliezar-Doyle et al. reveal that chronic pain involves astrocyte metabolic and translational reprogramming that shifts from acute remodelling to chronic mitochondrial dysfunction and lipid accumulation.
- Kunitomi et al. demonstrate that eIF4G2 controls intestinal stem cell identity through selective translation of epigenetic regulators driving fetal-like reprogramming.
In vivo single-cell ribosome profiling reveals cell-type-specific translational programs during aging
Molecular Cell, 2026
Duré, C., Ghoshdastider, U., Weber, R., Khandekar, A., Valdivia-Francia, F., Renz, P.F., Sella, F., Hyams, K., Taborsky, D., Yigit, M., Ormiston, M., Yamahachi, H., Levesque, M., Ellis, S.J. and Sendoel, A.
Stem cells maintain tissue homeostasis through two defining properties: lifelong self-renewal and the ability to differentiate into specialized cell types. These functions depend on tightly regulated gene expression, particularly at the level of translation. Despite high ribosome biogenesis, stem cells typically exhibit low global protein synthesis rates, largely through suppression of mTOR signalling and activation of translational repressors such as 4E-BPs. This restrained translational state is linked to stemness, regenerative capacity, and longevity. Upon activation and differentiation, mTOR signalling increases protein synthesis to support cell fate transitions. Ribosome profiling has revolutionized the study of translation by enabling genome-wide analysis of ribosome occupancy, but traditional approaches require large cell numbers, limiting studies of rare stem cell populations. Emerging single-cell and in vivo ribosome profiling approaches now offer new opportunities to uncover how aging reshapes stem-cell translational landscapes and regenerative function.
Using in vivo single-cell ribosome profiling combined with scRNA-seq, the study mapped cell-type-specific translational landscapes in young and aged mouse epidermis. UMAP clustering of ~1,800 cells revealed distinct epidermal stem, suprabasal, follicular, immune, and pigment cell populations, with clear cell-type-specific translation of marker genes (e.g., Krt14 in stem cells, Krt10 in suprabasal cells). Global ribosome footprint counts and OPP assays indicated lower protein synthesis in epidermal stem cells compared to differentiated cells, with translation increasing during differentiation commitment. Integration of Ribo-seq and RNA-seq enabled calculation of translational efficiency (TE) per cell type. In aging, epidermal stem cells showed prominent TE rewiring rather than broad transcriptional changes, including strong upregulation of AP-1 transcription factor subunits (Jun, Fos, Atf4), driven in part by uORF and 5′ UTR-dependent mechanisms and linked to mTOR regulation. These translational shifts were validated by proteomics, immunostaining, and FACS-based protein quantification. Functionally, aging was associated with reduced TE of adhesion and signalling genes (e.g., E-cadherin, semaphorins), reshaping intercellular communication networks. Overall, the data reveal widespread, cell-type-specific translational reprogramming as a key feature of epidermal aging.
Learn more about EIRNABio’s ribosome profiling services here.
Translatome profiling of spinal cord astrocytes reveals distinct gene signatures associated with acute and chronic pain
iScience, 2026
Siliezar-Doyle, J., Perez, R.K., Stauffenberg, E., Nippert, A.R. and Tawfik, V.L.
Chronic pain affects around 20% of the global population, yet the mechanisms driving the transition from acute to persistent pain remain poorly understood. Increasing evidence points to spinal cord astrocytes, abundant glial cells that regulate neuronal signalling, metabolism, and synaptic function, as key contributors to this process. Following injury, astrocytes undergo reactive astrogliosis, altering their molecular and physiological state in ways that can promote pain hypersensitivity and central sensitization. Experimental manipulation of astrocytes alone is sufficient to induce pain-like responses, highlighting their therapeutic potential. However, studying astrocytes is technically challenging due to difficulties in isolating them, limiting our understanding of their injury-specific molecular signatures. Emerging transcriptomic and ribosome-affinity approaches are now beginning to reveal the regional and temporal heterogeneity of spinal astrocytes in chronic pain. Here, the authors utilise a RiboTag-based approach to examine the influence of translation of these processes.
Using a tibial fracture-cast mouse model of chronic pain, researchers investigated how spinal cord astrocytes change during the transition from acute to chronic pain. Behavioural assays showed that peripheral inflammation resolved by 5 weeks post-injury, while mechanical hypersensitivity persisted, defining distinct acute and chronic phases. To profile astrocyte-specific translation, the study used translating ribosome affinity purification (TRAP), which enabled immunoprecipitation of HA-tagged astrocytic ribosomes and sequencing of actively translated mRNAs. Immunostaining confirmed strong astrocyte specificity of the isolation strategy. Differential expression analysis and weighted gene correlation network analysis (WGCNA) revealed temporally distinct astrocyte translatomes: acute-phase astrocytes showed pronounced changes in cytoskeletal remodelling, ribosome biogenesis, and protein translation, alongside altered lipid metabolism and fatty acid β-oxidation pathways. In contrast, chronic-phase astrocytes displayed signatures of mitochondrial dysfunction and impaired oxidative phosphorylation. Finally, PLIN2 immunohistochemistry demonstrated accumulation of lipid droplets in the spinal cord during chronic pain, linking early metabolic disruption to long-term astrocyte pathology and persistent pain states.
Learn more about EIRNABio’s ribosome profiling services here.
eIF4G2-mediated selective translation of chromatin regulators safeguards adult intestinal stem cell identity and differentiation
Cell Stem Cell, 2026
Kunitomi, H., Khaine, A.M., Jamee, R., Arreola, V., Lancero, M., Raychaudhuri, A., Perli, S., Sato, Y., Iwasaki, M., Ruivo, P., Tomoda, K., Mito, M., Shichino, Y., Iwasaki, S. and Yamanaka, S.
Translation initiation is dynamically remodeled during development, stress adaptation, and tissue regeneration, allowing cells to rapidly alter protein production and cell identity. This study focuses on eIF4G2 (also known as DAP5/NAT1), a non-canonical translation initiation factor thought to selectively promote translation of mRNAs with complex regulatory features such as structured 5′ UTRs and upstream open reading frames. Although eIF4G2 has been linked to selective translational control, its physiological role in adult tissues has remained unclear because complete knockout is embryonically lethal. To address this, researchers generated an inducible loss-of-function model and examined the intestinal epithelium, where rapidly cycling Lgr5+ intestinal stem cells require tightly regulated translation to balance self-renewal and differentiation. Disruption of stem cell identity can trigger a regenerative fetal-like program associated with YAP/TAZ-TEAD signaling, providing a framework to investigate how translational rewiring influences tissue plasticity and regeneration. Here, the authors utilise ribosome profiling, amongst other techniques, to investigate these processes further.
Using a tamoxifen-inducible conditional knockout strategy in mice, the study first generated a systemic and intestinal epithelium-specific loss-of-function model for the translation initiation factor eIF4G2. Histology, RNAscope, and immunostaining showed that Eif4g2 deletion leads to rapid depletion of Lgr5+ intestinal stem cells and secretory lineages, while inducing a fetal-like, YAP/TAZ-associated regenerative program. These findings were validated across bulk RNA-seq, single-nucleus multiome profiling, and organoid cultures, all of which consistently revealed loss of canonical ISC programs, expansion of Bmi1+ fetal-like states, and impaired lineage maturation, particularly in secretory cells. Ribosome profiling combined with proteomics demonstrated that global translation remains largely unchanged, but eIF4G2 selectively promotes translation of long 5′UTR transcripts, including key chromatin regulators CREBBP and EP300. Reduced translation of these KAT3 enzymes led to decreased H3K18/H3K27 acetylation and genome-wide chromatin remodeling, with loss of ISC enhancers and gain of YAP/fetal regulatory elements. Pharmacological inhibition of CREBBP/EP300 phenocopied the transcriptional and morphological effects, linking selective translation control to epigenetic and regenerative reprogramming.
Learn more about EIRNABio’s ribosome profiling services here.
