bims-ginsta Biomed News
on Genome instability
Issue of 2024–12–29
fourteen papers selected by
Jinrong Hu, National University of Singapore
  1. Single-cell analysis of bidirectional reprogramming between early embryonic states identify mechanisms of differential lineage plasticities in mice.
  2. Synthetic organizer cells guide development via spatial and biochemical instructions.
  3. Global versus local matrix remodeling drives rotational versus invasive collective migration of epithelial cells.
  4. Cited4a limits cardiomyocyte dedifferentiation and proliferation during zebrafish heart regeneration.
  5. Structural determinants of co-translational protein complex assembly.
  6. G3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatability.
  7. Genome concentration limits cell growth and modulates proteome composition in Escherichia coli.
  8. RNA sensing induced by chromosome missegregation augments anti-tumor immunity.
  9. Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries.
  10. Nucleolar protein PEXF controls ribosomal RNA synthesis and pluripotency exit.
  11. Mitochondrial DNA mutations in human oocytes undergo frequency-dependent selection but do not increase with age.
  12. Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites.
  13. Mechanical signaling through membrane tension induces somal translocation during neuronal migration.
  14. Spatiotemporal single-cell roadmap of human skin wound healing.
  1. Dev Cell. 2024 Dec 19. pii: S1534-5807(24)00722-6. [Epub ahead of print]
    Single-cell analysis of bidirectional reprogramming between early embryonic states identify mechanisms of differential lineage plasticities in mice.
    Vidur Garg, Yang Yang, Sonja Nowotschin, Manu Setty, Eralda Salataj, Ying-Yi Kuo, Dylan Murphy, Roshan Sharma, Amy Jang, Alexander Polyzos, Dana Pe'er, Effie Apostolou, Anna-Katerina Hadjantonakis.
      Two distinct lineages, pluripotent epiblast (EPI) and primitive (extra-embryonic) endoderm (PrE), arise from common inner cell mass (ICM) progenitors in mammalian embryos. To study how these sister identities are forged, we leveraged mouse embryonic stem (ES) cells and extra-embryonic endoderm (XEN) stem cells-in vitro counterparts of the EPI and PrE. Bidirectional reprogramming between ES and XEN coupled with single-cell RNA and ATAC-seq analyses showed distinct rates, efficiencies, and trajectories of state conversions, identifying drivers and roadblocks of reciprocal conversions. While GATA4-mediated ES-to-iXEN conversion was rapid and nearly deterministic, OCT4-, KLF4-, and SOX2-induced XEN-to-induced pluripotent stem (iPS) reprogramming progressed with diminished efficiency and kinetics. A dominant PrE transcriptional program, safeguarded by GATA4, alongside elevated chromatin accessibility and reduced DNA methylation of the EPI underscored the differential plasticities of the two states. Mapping in vitro to embryo trajectories tracked reprogramming cells in either direction along EPI and PrE in vivo states, without transitioning through the ICM.
    Keywords:  ES cells; XEN cells; blastocyst; epiblast; extra-embryonic endoderm; lineage plasticity; pluripotency; primitive endoderm; reprogramming; single-cell analysis
    DOI:  https://doi.org/10.1016/j.devcel.2024.11.022
  2. Cell. 2024 Dec 11. pii: S0092-8674(24)01323-0. [Epub ahead of print]
    Synthetic organizer cells guide development via spatial and biochemical instructions.
    Toshimichi Yamada, Coralie Trentesaux, Jonathan M Brunger, Yini Xiao, Adam J Stevens, Iain Martyn, Petr Kasparek, Neha P Shroff, Angelica Aguilar, Benoit G Bruneau, Dario Boffelli, Ophir D Klein, Wendell A Lim.
      In vitro development relies primarily on treating progenitor cells with media-borne morphogens and thus lacks native-like spatial information. Here, we engineer morphogen-secreting organizer cells programmed to self-assemble, via cell adhesion, around mouse embryonic stem (ES) cells in defined architectures. By inducing the morphogen WNT3A and its antagonist DKK1 from organizer cells, we generated diverse morphogen gradients, varying in range and steepness. These gradients were strongly correlated with morphogenetic outcomes: the range of minimum-maximum WNT activity determined the resulting range of anterior-to-posterior (A-P) axis cell lineages. Strikingly, shallow WNT activity gradients, despite showing truncated A-P lineages, yielded higher-resolution tissue morphologies, such as a beating, chambered cardiac-like structure associated with an endothelial network. Thus, synthetic organizer cells, which integrate spatial, temporal, and biochemical information, provide a powerful way to systematically and flexibly direct the development of ES or other progenitor cells in different directions within the morphogenetic landscape.
    Keywords:  developmental biology; differential adhesion; gastruloid; morphogen gradient; regenerative medicine; signaling center; synCAMs; synthetic biology; synthetic cell adhesion molecules; synthetic embryos; synthetic organizer
    DOI:  https://doi.org/10.1016/j.cell.2024.11.017
  3. Dev Cell. 2024 Dec 17. pii: S1534-5807(24)00721-4. [Epub ahead of print]
    Global versus local matrix remodeling drives rotational versus invasive collective migration of epithelial cells.
    Sural K Ranamukhaarachchi, Alyssa Walker, Man-Ho Tang, William D Leineweber, Sophia Lam, Wouter-Jan Rappel, Stephanie I Fraley.
      The coordinated movement of cell collectives is essential for normal epithelial tissue development, maintenance, and cancer progression. Here, we report on a minimal 3D extracellular matrix (ECM) system wherein both invasive collective migration (ICM) and rotational collective migration (RCM) arise spontaneously from individually seeded epithelial cells of mammary and hepatic origin, regardless of whether they express adherens junctions, and lead to ductal-like and acinar-like structures, respectively. Quantitative microscopy and cellular Potts modeling reveal that initial differences in cell protrusion dynamics and matrix-remodeling localization generate RCM and ICM behavior in confining 3D ECM. Matrix-remodeling activity by matrix metalloproteinases (MMPs) is localized to the base of protrusions in cells that initiate ICM, whereas RCM does not require MMPs and is associated with ITGβ1-mediated remodeling localized globally around the cell body. Further analysis in vitro and in vivo supports the concept that distinct matrix-remodeling strategies encode collective migration behaviors and tissue structure.
    Keywords:  ITGβ1; MT1-MMP; adherens junctions; adhesion; collective migration; invasive migration; matrix metalloproteinase; matrix remodeling; rotational migration
    DOI:  https://doi.org/10.1016/j.devcel.2024.11.021
  4. bioRxiv. 2024 Dec 09. pii: 2024.12.05.626917. [Epub ahead of print]
    Cited4a limits cardiomyocyte dedifferentiation and proliferation during zebrafish heart regeneration.
    Rachel Forman-Rubinsky, Wei Feng, Brent T Schlegel, Angela Paul, Daniel Zuppo, Katarzyna Kedziora, Donna Stoltz, Simon Watkins, Dhivyaa Rajasundaram, Guang Li, Michael Tsang.
      Cardiac regeneration involves the interplay of complex interactions between many different cell types, including cardiomyocytes. The exact mechanism that enables cardiomyocytes to undergo dedifferentiation and proliferation to replace lost cells has been intensely studied. Here we report a single nuclear RNA sequencing profile of the injured zebrafish heart and identify distinct cardiomyocyte populations in the injured heart. These cardiomyocyte populations have diverse functions, including stress response, myofibril assembly, proliferation and contraction. The contracting cardiomyocyte population also involves the activation of maturation pathways as an early response to injury. This intriguing finding suggests that constant maintenance of a distinctive terminally differentiated cardiomyocyte population is important for cardiac function during regeneration. To test this hypothesis, we determined that cited4a, a p300/CBP transcriptional coactivator, is induced after injury in the mature cardiomyocyte population. Moreover, loss-of- cited4a mutants presented increased dedifferentiation, proliferation and accelerated heart regeneration. Thus, suppressing cardiomyocyte maturation pathway activity in injured hearts could be an approach to promote heart regeneration.
    DOI:  https://doi.org/10.1101/2024.12.05.626917
  5. Cell. 2024 Dec 18. pii: S0092-8674(24)01330-8. [Epub ahead of print]
    Structural determinants of co-translational protein complex assembly.
    Saurav Mallik, Johannes Venezian, Arseniy Lobov, Meta Heidenreich, Hector Garcia-Seisdedos, Todd O Yeates, Ayala Shiber, Emmanuel D Levy.
      Protein assembly into functional complexes is critical to life's processes. While complex assembly is classically described as occurring between fully synthesized proteins, recent work showed that co-translational assembly is prevalent in human cells. However, the biological basis for the existence of this process and the identity of protein pairs that assemble co-translationally remain unknown. We show that co-translational assembly is governed by structural characteristics of complexes and involves mutually stabilized subunits. Accordingly, co-translationally assembling subunits are unstable in isolation and exhibit synchronized proteostasis with their partner. By leveraging structural signatures and AlphaFold2-based predictions, we accurately predicted co-translational assembly, including pair identities, at proteome scale and across species. We validated our predictions by ribosome profiling, stoichiometry perturbations, and single-molecule RNA-fluorescence in situ hybridization (smFISH) experiments that revealed co-localized mRNAs. This work establishes a fundamental connection between protein structure and the translation process, highlighting the overarching impact of three-dimensional structure on gene expression, mRNA localization, and proteostasis.
    Keywords:  AlphaFold; co-translational assembly; mRNA localization; protein complexes; protein interactions; protein structure; proteostasis; ribosome profiling; single-molecule FISH; translational regulation
    DOI:  https://doi.org/10.1016/j.cell.2024.11.013
  6. Mol Cell. 2024 Dec 19. pii: S1097-2765(24)00994-8. [Epub ahead of print]
    G3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatability.
    Irmela R E A Trussina, Andreas Hartmann, Christine Desroches Altamirano, Janani Natarajan, Charlotte M Fischer, Marta Aleksejczuk, Hannes Ausserwöger, Tuomas P J Knowles, Michael Schlierf, Titus M Franzmann, Simon Alberti.
      Ribonucleoprotein (RNP) granules have been linked to translation regulation and disease, but their assembly and regulatory mechanisms are not well understood. Here, we show that the RNA-binding protein G3BP1 preferentially interacts with unfolded RNA, driving the assembly of RNP granule-like condensates that establish RNA-RNA interactions. These RNA-RNA interactions limit the mobility and translatability of sequestered mRNAs and stabilize the condensates. The DEAD-box RNA helicase DDX3X attenuates RNA-RNA interactions inside RNP granule-like condensates, rendering the condensates dynamic and enabling mRNA translation. Importantly, disease-associated and catalytically inactive DDX3X variants fail to resolve such RNA-RNA interactions. Inhibiting DDX3X in cultured cells accelerates RNP granule assembly and delays their disassembly, indicating that RNA-RNA interactions contribute to RNP granule stability in cells. Our findings reveal how RNP granules generate inhibitory RNA-RNA interactions that are modulated by DEAD-box RNA helicases to ensure RNA availability and translatability.
    Keywords:  DDX3X; DEAD-box helicase; G3BP1; RNA-RNA interactions; RNP granule; biomolecular condensate; stress granule
    DOI:  https://doi.org/10.1016/j.molcel.2024.11.039
  7. Elife. 2024 Dec 23. pii: RP97465. [Epub ahead of print]13
    Genome concentration limits cell growth and modulates proteome composition in Escherichia coli.
    Jarno Mäkelä, Alexandros Papagiannakis, Wei-Hsiang Lin, Michael Charles Lanz, Skye Glenn, Matthew Swaffer, Georgi K Marinov, Jan M Skotheim, Christine Jacobs-Wagner.
      Defining the cellular factors that drive growth rate and proteome composition is essential for understanding and manipulating cellular systems. In bacteria, ribosome concentration is known to be a constraining factor of cell growth rate, while gene concentration is usually assumed not to be limiting. Here, using single-molecule tracking, quantitative single-cell microscopy, and modeling, we show that genome dilution in Escherichia coli cells arrested for DNA replication limits total RNA polymerase activity within physiological cell sizes across tested nutrient conditions. This rapid-onset limitation on bulk transcription results in sub-linear scaling of total active ribosomes with cell size and sub-exponential growth. Such downstream effects on bulk translation and cell growth are near-immediately detectable in a nutrient-rich medium, but delayed in nutrient-poor conditions, presumably due to cellular buffering activities. RNA sequencing and tandem-mass-tag mass spectrometry experiments further reveal that genome dilution remodels the relative abundance of mRNAs and proteins with cell size at a global level. Altogether, our findings indicate that chromosome concentration is a limiting factor of transcription and a global modulator of the transcriptome and proteome composition in E. coli. Experiments in Caulobacter crescentus and comparison with eukaryotic cell studies identify broadly conserved DNA concentration-dependent scaling principles of gene expression.
    Keywords:  Caulobacter crescentus; E. coli; cell biology; cell growth; limitation; proteome allocation; ribosomes; transcription
    DOI:  https://doi.org/10.7554/eLife.97465
  8. Mol Cell. 2024 Dec 10. pii: S1097-2765(24)00950-X. [Epub ahead of print]
    RNA sensing induced by chromosome missegregation augments anti-tumor immunity.
    Nobunari Sasaki, Mizuki Homme, Takahiko Murayama, Tatsuya Osaki, Toshiyuki Tenma, Tadaichi An, Yujiro Takegami, Tetsuo Tani, Patrick C Gedeon, Yoshihisa Kobayashi, Israel Cañadas, David A Barbie, Ryoji Yao, Shunsuke Kitajima.
      Viral mimicry driven by endogenous double-stranded RNA (dsRNA) stimulates innate and adaptive immune responses. However, the mechanisms that regulate dsRNA-forming transcripts during cancer therapy remain unclear. Here, we demonstrate that dsRNA is significantly accumulated in cancer cells following pharmacologic induction of micronuclei, stimulating mitochondrial antiviral signaling (MAVS)-mediated dsRNA sensing in conjunction with the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. Activation of cytosolic dsRNA sensing cooperates with double-stranded DNA (dsDNA) sensing to upregulate immune cell migration and antigen-presenting machinery. Tracing of dsRNA-sequences reveals that dsRNA-forming transcripts are predominantly generated from non-exonic regions, particularly in locations proximal to genes exhibiting high chromatin accessibility. Activation of this pathway by pulsed monopolar spindle 1 (MPS1) inhibitor treatment, which potently induces micronuclei formation, upregulates cytoplasmic dsRNA sensing and thus promotes anti-tumor immunity mediated by cytotoxic lymphocyte activation in vivo. Collectively, our findings uncover a mechanism in which dsRNA sensing cooperates with dsDNA sensing to boost immune responses, offering an approach to enhance the efficacy of cancer therapies targeting genomic instability.
    Keywords:  MAVS; Mps1; STING; cGAS; chromosome missegregation; dsRNA; micronuclei; tumor immunity; type I interferon
    DOI:  https://doi.org/10.1016/j.molcel.2024.11.025
  9. Cell Rep. 2024 Dec 24. pii: S2211-1247(24)01444-X. [Epub ahead of print]44(1): 115093
    Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries.
    Chow Hiang Ang, Philip Arandjelovic, Jinming Cheng, Jicheng Yang, Fusheng Guo, Yuanquan Yu, Sarmilla Nelameham, Lachlan Whitehead, Jiangtao Li, David L Silver, Nick Barker, Jane E Visvader, Pierce K H Chow, Gordon K Smyth, Yunshun Chen, David M Virshup, Nai Yang Fu.
      Hepatocytes are organized into distinct zonal subsets across the liver lobule, yet their contributions to liver homeostasis and regeneration remain controversial. Here, we developed multiple genetic lineage-tracing mouse models to systematically address this. We found that the liver lobule can be divided into two major zonal and molecular hepatocyte populations marked by Cyp2e1 or Gls2. Pericentral Cyp2e1+ and periportal Gls2+ hepatocytes maintain their own lineage during adult homeostasis, while Cyp2e1+ hepatocytes fuel neonatal liver growth. The Gls2+ and Cyp2e1+ populations can rapidly regenerate one another when one of the populations is severely damaged. Midlobular Ccnd1+ hepatocytes are enriched in the Cyp2e1+ zone in adult liver but have limited contributions to regeneration upon partial hepatectomy and severe pericentral injury. Remarkably, Lgr5+ hepatocytes, a unique Cyp2e1+ subset, contribute significantly to liver replenishment upon periportal injuries. Our findings unravel that zonal hepatocytes mainly self-maintain during homeostasis but exhibit complex plasticity in repair upon injury.
    Keywords:  CP: Stem cell research; cell plasticity; hepatocyte; lineage tracing; liver development; liver homeostasis; liver injury; liver lobule; liver regeneration; liver zonation; stem cells
    DOI:  https://doi.org/10.1016/j.celrep.2024.115093
  10. Dev Cell. 2024 Dec 18. pii: S1534-5807(24)00726-3. [Epub ahead of print]
    Nucleolar protein PEXF controls ribosomal RNA synthesis and pluripotency exit.
    Zihao Li, Siwen Chen, Sifang Li, Hua Chao, Wenjun Hao, Shuai Zhang, Zemin Li, Jianru Wang, Xiang Li, Yong Wan, Hui Liu.
      Maintenance and exit from pluripotency of embryonic stem cells (ESCs) are controlled by highly coordinated processes of protein synthesis and ribosome biogenesis (RiBi). ESCs are characterized by low rates of global protein synthesis and high levels of RiBi. Transient reduction of RiBi is a characteristic molecular event during the exit from pluripotency, of which the regulatory mechanism is unclear. Here, we identify that a previously uncharacterized nucleolar protein, pluripotency exit factor (PEXF), encoded by long noncoding RNA LINC00472, plays a role in the transient reduction of RiBi. PEXF dissociates RNA polymerase I from the rDNA through interaction with the rDNA promoter region in a liquid-liquid phase separation-dependent manner, therefore inhibiting the production of pre-ribosomal RNA, a key component of ribosomes. This finding reveals a potential mechanism of exit from pluripotency gated by ribosome levels in human ESCs.
    Keywords:  RNA polymerase I; liquid-liquid phase separation; novel protein; pluripotency exit; ribosomal RNA
    DOI:  https://doi.org/10.1016/j.devcel.2024.12.004
  11. bioRxiv. 2024 Dec 12. pii: 2024.12.09.627454. [Epub ahead of print]
    Mitochondrial DNA mutations in human oocytes undergo frequency-dependent selection but do not increase with age.
    Barbara Arbeithuber, Kate Anthony, Bonnie Higgins, Peter Oppelt, Omar Shebl, Irene Tiemann-Boege, Francesca Chiaromonte, Thomas Ebner, Kateryna D Makova.
      Mitochondria, cellular powerhouses, harbor DNA (mtDNA) inherited from the mothers. MtDNA mutations can cause diseases, yet whether they increase with age in human germline cells-oocytes-remains understudied. Here, using highly accurate duplex sequencing of full-length mtDNA, we detected de novo mutations in single oocytes, blood, and saliva in women between 20 and 42 years of age. We found that, with age, mutations increased in blood and saliva but not in oocytes. In oocytes, mutations with high allele frequencies (≥1%) were less prevalent in coding than non-coding regions, whereas mutations with low allele frequencies (<1%) were more uniformly distributed along mtDNA, suggesting frequency-dependent purifying selection. In somatic tissues, mutations caused elevated amino acid changes in protein-coding regions, suggesting positive or destructive selection. Thus, mtDNA in human oocytes is protected against accumulation of mutations having functional consequences and with aging. These findings are particularly timely as humans tend to reproduce later in life.
    DOI:  https://doi.org/10.1101/2024.12.09.627454
  12. Cell. 2024 Dec 18. pii: S0092-8674(24)01345-X. [Epub ahead of print]
    Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites.
    Lorena Benedetti, Ruolin Fan, Aubrey V Weigel, Andrew S Moore, Patrick R Houlihan, Mark Kittisopikul, Grace Park, Alyson Petruncio, Philip M Hubbard, Song Pang, C Shan Xu, Harald F Hess, Stephan Saalfeld, Vidhya Rangaraju, David E Clapham, Pietro De Camilli, Timothy A Ryan, Jennifer Lippincott-Schwartz.
      Neuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at ∼1 μm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca2+ channels and ER Ca2+-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca2+ homeostasis, and local activation of the Ca2+/calmodulin-dependent protein kinase II. Local spine stimulation activates the Ca2+ modulatory machinery, facilitating signal transmission and ryanodine-receptor-dependent Ca2+ release at ER-PM junctions over 20 μm away. Thus, interconnected ER-PM junctions support signal propagation and Ca2+ release from the spine-adjacent ER. The capacity of this subcellular architecture to modify both local and distant membrane-proximal biochemistry potentially contributes to dendritic computations.
    Keywords:  Ca(2+)/calmodulin-dependent protein kinase II; CaMKII; Drosophila melanogaster; ER-PM junctions; Junctophilin; RyRs; VGCC; endoplasmic reticulum; hippocampal neurons; ryanodine receptors; voltage-gated calcium channels; volume electron microscopy
    DOI:  https://doi.org/10.1016/j.cell.2024.11.029
  13. EMBO J. 2024 Dec 20.
    Mechanical signaling through membrane tension induces somal translocation during neuronal migration.
    Takunori Minegishi, Honami Hasebe, Tomoya Aoyama, Keiji Naruse, Yasufumi Takahashi, Naoyuki Inagaki.
      Neurons migrate in a saltatory manner by repeating two distinct steps: extension of the leading process and translocation of the cell body. The former step is critical for determining the migratory route in response to extracellular guidance cues. In the latter step, neurons must generate robust forces that translocate the bulky soma against mechanical barriers of the surrounding three-dimensional environment. However, the link between the leading process extension and subsequent somal translocation remains unknown. By using the membrane tension sensor Flipper-TR and scanning ion conductance microscopy, we show that leading process extension increases plasma membrane tension. The tension elevation activated the mechanosensitive ion channel Tmem63b and triggered Ca2+ influx, leading to actomyosin activation at the rear of the cell. Blockade of this signaling pathway disturbed somal translocation, thereby inhibiting neuronal migration in three-dimensional environments. These data suggest that mechanical signaling through plasma membrane tension and mechano-channels links the leading process extension to somal translocation, allowing rapid and saltatory neuronal migration.
    Keywords:  Mechanosensing; Mechanosensitive Ion Channel; Myosin II; Neuronal Migration; Plasma Membrane Tension
    DOI:  https://doi.org/10.1038/s44318-024-00326-8
  14. Cell Stem Cell. 2024 Dec 18. pii: S1934-5909(24)00412-0. [Epub ahead of print]
    Spatiotemporal single-cell roadmap of human skin wound healing.
    Zhuang Liu, Xiaowei Bian, Lihua Luo, Åsa K Björklund, Li Li, Letian Zhang, Yongjian Chen, Lei Guo, Juan Gao, Chunyan Cao, Jiating Wang, Wenjun He, Yunting Xiao, Liping Zhu, Karl Annusver, Nusayhah Hudaa Gopee, Daniela Basurto-Lozada, David Horsfall, Clare L Bennett, Maria Kasper, Muzlifah Haniffa, Pehr Sommar, Dongqing Li, Ning Xu Landén.
      Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell multi-omics analyses on human skin wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations.
    Keywords:  acute wound; chronic wounds; diabetic foot ulcer; scRNA-seq; spatial transcriptomics; venous ulcer; wound healing
    DOI:  https://doi.org/10.1016/j.stem.2024.11.013
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