5: Growth and Differentiation of the Epidermis Flashcards
What are the characteristics of epidermal stem cells?
Progenitor cells that can renew and give rise to differentiated progeny. Putative stem cells that self-renew robustly. Markers include B1 integrin, LRIG1, and CD46.
What is the role of the epidermal stem cell niche?
It is the tissue environment where stem cells exist, located throughout the basal layer or at the tops/bottoms of rete ridges.
How does epidermal proliferation contribute to skin health?
It involves continuous proliferation for homeostatic turnover, occurring approximately every 2 weeks. It plays a crucial role in wound healing.
What are the key features of basal cells in the epidermis?
Express Keratin 5 and 14. Show increased levels of Dsg3. Form cell-cell adhesions through desmosomes and adherens junctions, giving rise to spinous cells.
What are the characteristics of spinous cells in the epidermis?
Express Keratin 1 and 10. Show increased levels of Dsg1. Exhibit upregulation of desmosomes, leading to a spiny appearance.
What are the functions of granular cells in the epidermis?
Contain keratohyalin granules, composed of keratins, profilaggrin, and loricrin. Profilaggrin is metabolized into Natural Moisturizing Factor for hydration and UV protection. Contribute to the epidermal differentiation complex on chromosome 1q21, which includes proteins like loricrin and involucrin.
What is the structure and function of the stratum corneum?
Composed of cornified envelopes that are acellular and anuclear. The core consists of keratins surrounded by crosslinked proteins, especially loricrin. Surrounded by lipids, including crosslinked ceramides, contributed by transglutaminase.
What role do transcriptional regulators play in epidermal differentiation?
p63: Controls epidermal specification and maintains basal cell fate and proliferation. Notch: Facilitates the transition of basal cells to spinous cells. GRHL3: Involved in barrier formation and regulation of transglutaminase 1.
How do epigenetic regulators influence epidermal differentiation?
DNA methylation: Suppresses expression of differentiation genes in the basal layer (DNMT1). Histone modifications: Organize chromosomal DNA and regulate gene expression through methylation and acetylation, promoting differentiation.
What are the components of posttranscriptional regulation in epidermal differentiation?
miRNA modulate the levels/translation of a number of target mRNAs. miR-203 in spinous cells represses p63, thus ensuring proper differentiation.
IncRNA such as ANCR, recruits histone
methytransferase to certain promoters and promotes basal cell fate. TINCR promotes differentiated cell fate, stabilizing the differentiation promoting mRNAs such as Klf4 and Grhl3.
A patient presents with a defect in the Claudin1 protein. What condition might they have, and how does this defect affect the epidermis?
The patient might have neonatal ichthyosis. The Claudin1 defect disrupts tight junctions, which are essential for cell-cell adhesion, restricting fluid/ion flow, and serving as a barrier to membrane diffusion.
How would a mutation in the p63 gene affect epidermal differentiation and basal cell maintenance?
A mutation in the p63 gene would impair the control of epidermal specification, basal cell fate maintenance, and the induction of differentiation, potentially leading to defective skin barrier formation.
If a researcher observes increased Dsg1 expression in a cell, what type of epidermal cell are they likely studying?
They are likely studying spinous cells, as these cells exhibit increased Dsg1 expression and upregulation of desmosomes, giving them a spiny appearance.
What would happen to the epidermis if DNMT1 activity is inhibited in the basal layer?
Inhibiting DNMT1 would lead to the loss of DNA methylation, resulting in the expression of differentiation genes in the basal layer, disrupting the balance between proliferation and differentiation.
A patient has a mutation in the GRHL3 gene. What epidermal function might be impaired, and why?
The patient might have impaired barrier formation because GRHL3 regulates transglutaminase 1, which is crucial for forming the epidermal barrier.
How does the metabolization of profilaggrin contribute to the skin’s hydration and UV protection?
Profilaggrin is metabolized into amino acids, pyrrolidone carboxylic acid, and urocanic acid, which are components of the Natural Moisturizing Factor (NMF) that provide hydration and UV protection.
What role does Notch signaling play in the transition of basal cells to spinous cells?
Notch signaling facilitates the transition of basal cells to spinous cells, promoting differentiation within the epidermis.
What structural feature of granular cells contributes to their role in the epidermal barrier?
Granular cells contain keratohyalin granules composed of keratins, profilaggrin, and loricrin, as well as tight junctions that restrict fluid/ion flow and act as a barrier to membrane diffusion.
How does histone acetylation influence epidermal differentiation?
Histone acetylation promotes epidermal differentiation by modifying chromosomal DNA organization, making differentiation genes more accessible for transcription.
What is the significance of the epidermal differentiation complex on chromosome 1q21?
The epidermal differentiation complex on chromosome 1q21 encodes proteins like loricrin, involucrin, and late cornified envelope proteins, which are essential for the structural integrity and function of the epidermis.
How do miRNAs like miR-203 regulate epidermal differentiation?
miR-203 represses p63 in spinous cells, thereby promoting differentiation and preventing the maintenance of basal cell characteristics.
What would be the consequence of a defect in transglutaminase activity in the stratum corneum?
A defect in transglutaminase activity would impair the crosslinking of ceramides and proteins, compromising the lipid barrier and structural integrity of the stratum corneum.
How does the basal layer’s expression of Keratin 5 and 14 contribute to its function?
Keratin 5 and 14 provide structural support and are essential for the basal layer’s role in giving rise to spinous cells and maintaining cell-cell adhesions through desmosomes and adherens junctions.
What is the role of ANCR and TINCR in epidermal differentiation?
ANCR promotes basal cell fate, while TINCR promotes differentiated cell fate, ensuring proper regulation of epidermal differentiation.
