Epigenetic Regulation of Stem Cell Plasticity in Tissue Regeneration and Disease

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Background

Stem cell plasticity is a fundamental mode of injury response in a variety of organs in vertebrates. Regeneration of injured tissues relies on the activity of adult stem cells, which often deviate from their normal lineage paths acquiring alternative fates that contribute to restore damaged or lost cells. However, cell fate plasticity may become, in certain circumstances, a double-edged sword, being a prerequisite of pathologic tissue transformations accompanying malignant and non-malignant pathologies. If on one hand this is crucial for an efficient tissue repair, the pathological persistence of pro-regenerative stimuli, or occurrence of oncogenic mutations, often leads to the acquisition of transformed phenotypes and loss of cellular commitment that culminates with tumors development. As such, the elucidation of the molecular events underlying stem cell plasticity is of crucial importance to understand how these mechanisms are aberrantly deregulated in disease and how their deregulation may lead to pathological phenotypes.

Stem cells’ lineage choice is a process finely governed epigenetically. Alternative developmental programs are either activated or repressed, in response to environmental cues, via the concerted action of tissue-specific transcription factors and chromatin modifying enzymes that regulate chromatin structure by inducing post-translational modifications of histones. In the last two decades, application of global epi-genomic approaches has dramatically increased our understanding on how epigenetic modifiers shape the transcriptional output of nearly all mammalian cells. The challenge now is to apply these approaches to finely understand the epigenetic mechanisms governing metaplastic cell fate changes during tissue regeneration and disease. Emerging technologies (i.e. single-cell transcriptomics) promises to provide new insights on how cell fate of even rare stem cells populations is epigenetically modulated in response to injury or in diseased conditions. Since chromatin modifying enzymes offer now a reservoir of possible druggable targets, we predict that expanding our knowledge on how these enzymes are involved in dictating stem cells fate choices will inspire next-generation epigenetic approaches to modulate cell fates therapeutically.

In this Research Topic, we welcome original research and review articles that will contribute to the understanding of how epigenetic mechanisms might be harnessed to effectively enhance stem cells plasticity during regeneration and physiological aging. Of particular interest will be also contributions addressing how epigenetic events contribute instead to pathological plasticity in cancer and degenerative diseases.

Keywords: Stem cells, epigenetics, cancer, chromatin, regeneration

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