The epigenome as a putative target for skin repair: the HDAC inhibitor Trichostatin A modulates myeloid progenitor plasticity and behavior and improves wound healing

Journal of Translational Medicine
Mariana CabanelKatia Carneiro

Abstract

The molecular pathways that drive bone marrow myeloid progenitors (BMMP) development are very well understood and include a tight controlled multi-stage gene hierarch. Monocytes are versatile cells that display remarkable plasticity and may give rise to specific subsets of macrophages to proper promote tissue homesostasis upon an injury. However, the epigenetic mechanisms that underlie monocyte differentiation into the pro-inflammatory Ly6Chigh or the repairing Ly6Clow subsets are yet to be elucidated. We have previously shown that Epigenetic mechanisms Histone Deacetylase (HDAC) dependent are crucial for monocyte behavior and plasticity and in this work, we propose that this same mechanism underlies BMMP plasticity upon an inflammatory challenge in vivo. BMMP were culture in the presence of GM-CSF alone or in combination with HDAC inhibitor (iHDAC) and phenotyped by flow cytometry, immune staining or western blot. iHDAC was topically added to skin wounds for 7 consecutive days and wound healing was monitored by flow cytometry and histopathological analysis. When BMMP were cultured in the presence of iHDAC, we showed that the CD11blow/Ly6Clow subset was the specific target of iHDAC that underwent chromatin hyperacetylation in v...Continue Reading

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Citations

Jun 10, 2020·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Christopher J LewisFiona M Wood
Mar 11, 2021·Experimental Dermatology·Irena PastarMarjana Tomic-Canic

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
biopsies
confocal microscopy
acetylation

Software Mentioned

ImageQuant
ImageJ
Fiji
FlowingSoftware
FACSDiva
GraphPad Prism

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