ex23q Flashcards
Two most important key properties of stem cells
- Self-renewal: Ability to divide and maintain an undifferentiated state. 2. Differentiation: Capability to develop into specialized cell types.
Three important criteria for pluripotency testing
- Expression of pluripotency markers like Oct4, Nanog, Sox2. 2. Ability to differentiate into all three germ layers (endoderm, mesoderm, ectoderm). 3. Formation of teratomas in immunodeficient mice.
Two subsets of cancer stem cells and their features
- Stationary CSCs: Found in the primary tumor, maintaining local growth. 2. Migratory CSCs: Responsible for metastasis, divide asymmetrically, and invade distant tissues.
Describe organoids and the critical steps in their formation
Organoids are self-organized 3D tissue-like structures derived from stem cells that mimic organ architecture and function. Steps: 1. Isolation and culture of stem cells. 2. Differentiation signals with extracellular matrix support. 3. Self-organization into a 3D structure.
Three areas where organoid models can be applied
- Disease modeling (e.g., cancer, genetic disorders). 2. Drug testing and toxicity screening. 3. Regenerative medicine and transplantation research.
Why are mutations less common in exons than introns?
Exons are under selective pressure as they encode proteins. Harmful mutations are eliminated through evolution, whereas introns are less constrained and tolerate mutations.
Variable expressivity and reduced penetrance
Variable expressivity: Same mutation causes varying severity of symptoms. Reduced penetrance: Not all individuals with the mutation express the phenotype.
Why do mitochondrial diseases display maternal inheritance?
Mitochondrial DNA is inherited exclusively from the mother because sperm mitochondria are degraded or excluded during fertilization.
Why are children of the same mother differentially affected by mitochondrial diseases?
Heteroplasmy: Different egg cells have varying proportions of mutated and normal mitochondria, leading to variable severity in offspring.
Define epigenetic writers, readers, and erasers with examples
Writers: Add marks (e.g., DNMTs, HATs). Readers: Recognize marks (e.g., bromodomains). Erasers: Remove marks (e.g., TET enzymes, HDACs).
Difference between de novo and maintenance DNA methylation
De novo: Establishes new methylation patterns (DNMT3A/B). Maintenance: Copies existing methylation patterns after replication (DNMT1).
Active and passive DNA demethylation
Active: Enzymatic removal by TET enzymes and BER (base excision repair) pathway. Passive: Loss of methylation due to lack of maintenance during replication.
Mechanism of FMR1 expression loss in Fragile X syndrome
CGG expansion (full mutuation: > 200 repeats) in the 5’UTR leads to CpG methylation, recruiting methyl-binding proteins that condense chromatin and silence transcription.
Three functions of endothelial cells in the vasculature
- Regulate vascular tone (e.g., nitric oxide production). 2. Maintain a selective barrier between blood and tissues. 3. Secrete antithrombotic and procoagulant factors.
What is atherosclerosis?
Atherosclerosis is the progressive buildup of lipid-filled plaques in arterial walls, causing inflammation and reduced blood flow.
How does atherosclerosis lead to myocardial infarction and stroke?
Plaque rupture triggers thrombosis, blocking blood flow to the heart (myocardial infarction) or brain (stroke).
Factors determining whether bacteria cause infection
- Pathogenicity/virulence of the bacteria. 2. Host immune response and susceptibility. 3. Environmental factors (e.g., site of exposure).
How does a bacterium become multi-resistant in one event?
By acquiring a plasmid carrying multiple resistance genes via horizontal gene transfer.
How does antibiotic resistance spread locally and globally?
Locally: Through direct contact, biofilms, or plasmid transfer. Globally: Via misuse in humans/animals, travel, and environmental contamination.
Three cell types in the TME and their functions
- Cytotoxic T-cells: Kill tumor cells. 2. TAMs (Tumor-Associated Macrophages): Promote immune suppression and angiogenesis. 3. CAFs (Cancer-Associated Fibroblasts): Support extracellular matrix and tumor invasion.
Why are TME conditions important in immune checkpoint therapy?
TME contains cells and ligands (e.g., PD-L1) that suppress T cell activity, reducing therapy efficacy. Resistance arises from low antigen expression, upregulation of alternative checkpoints, or increased suppressive cells like Tregs and MDSCs.
