Regeneration depends on the ability of mature cells at the injury site to respond to injury, generating tissue-specific progenitors that incorporate the blastema and proliferate to reconstitute the original organ architecture. The metabolic microenvironment has been tightly connected to cell function and identity during development and tumorigenesis. Yet, the link between metabolism and cell identity at the mechanistic level in a regenerative context remains unclear. The adult zebrafish caudal fin, and bone cells specifically, have been crucial for the understanding of mature cell contribution to tissue regeneration. Here, we use this model to explore the relevance of glucose metabolism for the cell fate transitions preceding new osteoblast formation and blastema assembly. We show that injury triggers a modulation in the metabolic profile at early stages of regeneration to enhance glycolysis at the expense of mitochondrial oxidation. This metabolic adaptation mediates transcriptional changes that make mature osteoblast amenable to be reprogramed into pre-osteoblasts and induces cell cycle re-entry and progression. Manipulation of the metabolic profile led to severe reduction of the pre-osteoblast pool, diminishing their capacity to generate new osteoblasts, and to a complete abrogation of blastema formation. Overall, our data indicate that metabolic alterations have a powerful instructive role in regulating genetic programs that dictate fate decisions and stimulate proliferation, thereby providing a deeper understanding on the mechanisms regulating blastema formation and bone regeneration.
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http://dx.doi.org/10.7554/eLife.76987 | DOI Listing |
Adv Mater
December 2024
Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Adult mammals are unable to regenerate bulky bone tissues, making large bone defects clinically challenging. Deer antler represents an exception to this rule, exhibiting the fastest bony growth in mammals, offering a unique opportunity to explore novel strategies for rapid bone regeneration. Here, a bone graft exploiting the biochemical, biophysical, and structural characteristics of antlers is constructed.
View Article and Find Full Text PDFUnlabelled: Understanding how mechanical stimulation from exercise influences cellular responses during tissue repair could enhance therapeutic strategies. We explored zebrafish caudal fin regeneration to study exercise impacts on a robust model of tissue regeneration. We used a swim tunnel to determine that exercise initiated during but not after blastema establishment impaired fin regeneration, including of the bony ray skeleton.
View Article and Find Full Text PDFNat Commun
November 2024
Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria.
Regeneration of missing body parts can be observed in diverse animal phyla, but it remains unclear to which extent these capacities rely on shared or divergent principles. Research into this question requires detailed knowledge about the involved molecular and cellular principles in suitable reference models. By combining single-cell RNA sequencing and mosaic transgenesis in the marine annelid Platynereis dumerilii, we map cellular profiles and lineage restrictions during posterior regeneration.
View Article and Find Full Text PDFInsect Biochem Mol Biol
December 2024
College of Life Science, Tianjin Normal University, Tianjin, 300387, China; Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, 300387, China. Electronic address:
Tissue regeneration is an efficient strategy developed by animals to compensate for damaged tissues, involving various types of progenitor cells. Deciphering the signal network that modulates the activity of these progenitors during regeneration is crucial for understanding the differences in regenerative capacities across species. In this study, we evaluated the expression profile and phenotypic function of Notch signaling during limb regeneration in arthropod Chinese mitten crabs.
View Article and Find Full Text PDFInt J Mol Sci
September 2024
Molecular and Genetic Laboratory, College of Life Science, Henan Normal University, 46# East of Construction Road, Xinxiang 453007, China.
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