ArticleProceedings of the National Academy of Sciences of the United States of America2021
Delineating the heterogeneity of matrix-directed differentiation toward soft and stiff tissue lineages via single-cell profiling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Nuclear mechanotransduction: tools for mechanical perturbation and chromatin characterization.Nucleus (Austin, Tex.) · 2026Review
- The Role of EVs in the Aging Hematopoietic System.Aging cell · 2026Review
- Matrix Stiffness Orchestrates Mesenchymal Stem Cell Lineage Commitment Toward Osteogenesis and Adipogenesis Through the PIEZO1/SP1/STC2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Machine learning-driven single-cell phenotyping in size-controlled microenvironmentsLab on a chip · 2026Article
- The Synthetic Extracellular Matrix as a Maestro of the In Vitro Stem Cell Niche: Orchestrating Fate and Function.Biomedicines · 2026Review
- Integrating ChromaLIVE™ dye with an AI-powered image analysis for real-time monitoring of human mesenchymal stem cells differentiation.Biochemistry and biophysics reports · 2025Article
- Extracellular vesicles in age-related diseases: disease pathogenesis, intervention, and biomarker.Stem cell research & therapy · 2025Review
- Identifying differentiation markers between dermal fibroblasts and adipose-derived mesenchymal stromal cells (AD-MSCs) in human visceral and subcutaneous tissues using single-cell transcriptomics.Stem cell research & therapy · 2025Article
- TiORegenerative biomaterials · 2025Article
- Targeting micromotion for mimicking natural bone healing by using NIPAM/NbBioactive materials · 2024Article
- Optimization strategies for mesenchymal stem cell-based analgesia therapy: a promising therapy for pain management.Stem cell research & therapy · 2024Review
- A Thy-1-negative immunofibroblast population emerges as a key determinant of fibrotic outcomes to biomaterials.Science advances · 2024Article
- Vascular architecture regulates mesenchymal stromal cell heterogeneity via P53-PDGF signaling in the mouse incisor.Cell stem cell · 2024Article
- Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1.Journal of nanobiotechnology · 2024Article
- Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells by Hydrogel Encapsulation.Cells · 2024Review
- Biophysical control of plasticity and patterning in regeneration and cancer.Cellular and molecular life sciences : CMLS · 2023Review
- Stiffness-induced cancer-associated fibroblasts are responsible for immunosuppression in a platelet-derived growth factor ligand-dependent manner.PNAS nexus · 2023Article
- New Insights into YAP/TAZ-TEAD-Mediated Gene Regulation and Biological Processes in Cancer.Cancers · 2023Review
- Towards single cell encapsulation for precision biology and medicine.Advanced drug delivery reviews · 2023Review
- "Slow walk" mimetic tensile loading maintains human meniscus tissue resident progenitor cells homeostasis in photocrosslinked gelatin hydrogel.Bioactive materials · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stromal/stem cells (MSCs) form a heterogeneous population of multipotent progenitors that contribute to tissue regeneration and homeostasis. MSCs assess extracellular elasticity by probing resistance to applied forces via adhesion, cytoskeletal, and nuclear mechanotransducers that direct differentiation toward soft or stiff tissue lineages. Even under controlled culture conditions, MSC differentiation exhibits substantial cell-to-cell variation that remains poorly characterized. By single-cell transcriptional profiling of nonconditioned, matrix-conditioned, and early differentiating cells, we identified distinct MSC subpopulations with distinct mechanosensitivities, differentiation capacities, and cell cycling. We show that soft matrices support adipogenesis of multipotent cells and early endochondral ossification of nonadipogenic cells, whereas intramembranous ossification and preosteoblast proliferation are directed by stiff matrices. Using diffusion pseudotime mapping, we outline hierarchical matrix-directed differentiation and perform whole-genome screening of mechanoresponsive genes. Specifically, top-ranked tropomyosin-1 is highly sensitive to stiffness cues both at RNA and protein levels, and changes in TPM1 expression determine the differentiation toward soft versus stiff tissue lineage. Consistent with actin stress fiber stabilization, tropomyosin-1 overexpression maintains YAP1 nuclear localization, activates YAP1 target genes, and directs osteogenic differentiation. Knockdown of tropomyosin-1 reversed YAP1 nuclear localization consistent with relaxation of cellular contractility, suppressed osteogenesis, activated early endochondral ossification genes after 3 d of culture in induction medium, and facilitated adipogenic differentiation after 1 wk. Our results delineate cell-to-cell variation of matrix-directed MSC differentiation and highlight tropomyosin-mediated matrix sensing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.