Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Keratin5-BMP4 Mechanosignaling Network Regulates Cell Cytoskeletal Reorganization and Chromatin Accessibility during Revascularization-Based Blastema Regeneration

Version 1 : Received: 22 April 2021 / Approved: 23 April 2021 / Online: 23 April 2021 (13:17:12 CEST)

A peer-reviewed article of this Preprint also exists.

Journal reference: Experimental Cell Research 2022, 113272
DOI: 10.1016/j.yexcr.2022.113272


Heart regeneration after myocardial infarction remains challenging in reconstruction of blood resupply system. Here, we find that in zebrafish heart after resection of the ventricular apex, the local myocardial cells and the clotted blood cells undergo cell remodeling process via cytoplasmic exocytosis and nuclear reorganization within revascularization-based blastema. The regenerative processes are visualized by spatiotemporal expression of three blastema representative factors (alpha-SMA- which marks for fibrogenesis, Flk1for angiogenesis/hematopoiesis, and Pax3a for remusculogensis),and two histone modifications (H3K9Ac and H3K9Me3 mark for chromatin remodeling). Using the cultured zebrafish embryonic fibroblasts we identify blastema fraction components and show that Krt5 peptide could link cytoskeleton network and BMP4 signaling pathway to regulate the transcription and chromatin accessibility at the blastema representative genes and bmp4 genes. Our study provides new mechanistic insights into the epithelial-dependent and revascularization-based blastema regeneration for potential myocardial infarction therapy.


blastema regeneration: epigenetic reprogramming; keratin; BMP signaling; myocardium resalvage; zebrafish


BIOLOGY, Anatomy & Morphology

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