Epigenetic Regulation of Stem Cell Differentiation

After the fusion of gametes, the resulting totipotent cell initiates a series of cell divisions and differentiations, generating over 200 distinct cell types with diverse functions. The process of cellular specialization and function during development is heavily influenced by epigenetic modifications. These include DNA methylation, histone modifications, and non-coding RNAs, which add layers of information without altering the DNA sequence. These modifications play a crucial role in either preventing or ensuring the establishment of specific cellular lineages. Therefore, understanding how dynamic epigenetic changes regulate stem cell fate, maintain epigenetic memory to preserve cell identity, and impact cell adaptability in response to changing environments is essential.

Human mesenchymal stem cells (hMSCs) are one of the most promising sources for the treatment of degenerative diseases, including spinal cord injury, myocardial infarction, and Parkinson´s, among others, due to their interesting capacity of self-renewal and differentiation into a wide array of more specialized cells. However, the proliferation rate and the aging of MSCs through the cultures could favor epigenetic alterations restricting stem cell fate. Furthermore, the epigenetic memory of the source tissue might determine the differentiation potential of hMSCs, which complicates what source we should choose for certain clinical applications.

Despite significant advancements in molecular research on mesenchymal stem cells, studies investigating the connection between the epigenome and phenotype remain specific to particular cell types or certain epigenetic markers. This gap highlights our incomplete understanding of how epigenetic factors are recruited to chromatin and how their interactions contribute to determining cell fate. As cell engineering techniques continue to evolve for inducing differentiation, reprogramming, and transdifferentiation, and with ongoing discoveries in epigenetic modifications, there is a critical need to expand our quantitative understanding of epigenetic processes. This expansion is crucial for unraveling how cells acquire and maintain their commitment and identity over time.

In this Research Topic, we encourage submissions of high-quality original research, brief reports, and reviews aimed at advancing our knowledge of epigenetic modifiers—such as readers, writers, and erasers—that shape the epigenetic landscape and influence cell fate decisions.

Authors should address current topics that describe and contribute to the field of knowledge about the epigenetic mechanisms of regulation during differentiation and development, the interaction regulatory pathways that are established, and their importance in understanding cellular mechanisms.

Specific subtopics include, but are not limited to:

• Regulatory mechanisms mediated by non-coding transcripts

• lncRNAs acting as master regulators in cell fate.

• MicroRNAs in pluripotency and induction of reprogramming.

• Novel insights in non-coding RNAs during MSCs differentiation.

• Involvement of ncRNAs in gene regulation during cell fate and development.

• Crosstalk between DNA methylation and histone modifications in gene regulation.

• Epigenetic regulation of transcription factors of MSCs during differentiation.

• Emerging epigenetic therapies for regenerative medicine.

• Role of histone modifications in cell fate determination.

• Epigenetic approaches to enhance tissue regeneration and repair in degenerative conditions.

• Epigenetic memory and its role in cellular identity maintenance.

• Epigenetic mechanisms underlying cellular senescence and aging.

• Technological advancements in studying single-cell epigenomics.

• Epigenetic mechanisms in stem cell niche regulation.

• Comparative epigenomics across species to understand evolutionary conservation.

• Epigenetic regulation of tissue-specific gene expression.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Systematic Review
• Technology and Code

Keywords: Cellular differentiation, Development, DNA methylation, Epigenetics, Gene regulation, Histone modification, non-coding RNAs, Stem cells

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.