ArticleNature aging2026
Targeting RhoA nuclear mechanoactivity rejuvenates aged hematopoietic stem cells.
Article in Nature aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- Article
- Mechanisms of Hematopoietic Stem Cell Aging and Emerging Rejuvenation Strategies.Stem cell reviews and reports · 2026Review
- Targeting BIRC6 rejuvenates hematopoietic stem cell aging and immunosenescence.Signal transduction and targeted therapy · 2026Article
- Article
- Hematopoietic stem cell aging: a review of transcriptional and multi-omics insights and potential paths for AI integration.Experimental & molecular medicine · 2026Review
- Implications of Rho GTPase signaling in cancer immunotherapy.Biochemical Society transactions · 2026Review
- Improving lymphopoiesis in aged bone marrow.Current opinion in hematology · 2026Review
- Transcriptional heterogeneity predicts and enables clonal selection in ageing haematopoiesis.Research square · 2026Article
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- Squishing, squeezing and stretching age hematopoietic stem cells.Nature aging · 2026Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Biomechanical alterations contribute to the decreased regenerative capacity of hematopoietic stem cells (HSCs) upon aging. RhoA is a key regulator of mechanosignaling, but its role in mechanotransduction in stem cell aging remains unclear. Here we show that murine HSCs respond to increased nuclear envelope (NE) tension by inducing NE translocation of P-cPLA2, which cell-intrinsically activates RhoA. Aged HSCs experience physiologically higher intrinsic NE tension, but reducing RhoA activity lowers NE tension in aged HSCs. Feature image analysis of HSC nuclei reveals that chromatin remodeling is associated with RhoA inhibition, including restoration of youthful levels of the heterochromatin marker H3K9me2 and a decrease in chromatin accessibility and transcription at retrotransposons. Finally, we demonstrate that RhoA inhibition upregulates Klf4 expression and transcriptional activity, improving aged HSC regenerative capacity and lympho/myeloid skewing in vivo. Together, our data outline an intrinsic RhoA-dependent mechanosignaling axis, which can be pharmacologically targeted to restore aged stem cell function.
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Registered trials
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