Epigenetic regulation by 5-hydroxymethylcytosine in atopic dermatitis and psoriasis and its implications for epidermal stem cell behavior

Far from being just an intermediary in the DNA demethylation pathway, 5- hydroxymethylcytosine (5-hmC) is an epigenetic marker that significantly influences gene expression, with major consequences for embryonic development, stem cell identity, and ultimately organ homeostasis. Keratinocyte stem cells (KSC) maintain a healthy skin barrier by replenishing dead keratinocytes lost during daily turnover, injury, or pathological disturbances. In atopic dermatitis (AD) and psoriasis (PS), there is marked psoriasiform hyperplasia of the epidermis, suggesting a hyperproliferation of keratinocytes and dysregulation of epidermal stem cells. Therefore, we are interested in how the relationship between 5-hmC level and KSC activity might contribute to the pathogenesis of these diseases. The most important finding of our investigation is the loss of 5-hmC in the PS epidermis that stands in stark contrast to the retention of 5-hmC in the AD epidermis, a result that is replicated in our imiquimod-induced PS mouse models and tape stripped, ovalbumin-induced AD mouse models. In PS, the loss of 5-hmC is accompanied by a loss of cytokeratin-15-labelled KSCs with significant expansion of transit-amplifying cells (TAC), which is not seen in AD. We also conduct proteomic digital spatial profiling of AD and PS mouse models in order to identify potential molecular drivers behind KSC dysregulation. Of note, CD11b, p53, and CD44 are proteins that exhibit significantly altered expression profiles that differentiate the AD models from control skin. These proteins have been implicated in signaling pathways that affect stem cell identity and stem cell activation. Therefore, modification of the 5-hmC landscape and expression of these proteins might aid in the management of these chronic dermatological conditions.

Author dc:creator

• Nguyen, Huy

Advisors dc:contributor.advisor

• Trinkaus-Randall, Vickery E.
• Lian, Christine G.

• Pathology
• Biology
• Medicine
• 5-hmC
• Atopic dermatitis
• Digital spatial profiling
• Proteomic
• Psoriasis
• Stem cell

Language dc:language.iso

en_US

Handle dc:identifier.uri

https://hdl.handle.net/2144/52311

OAI identifier oai:identifier

oai:open.bu.edu:2144/52311