Development, stem cells, and cancer

🔹 Regeneration

Q: What organism is an excellent model for studying regeneration?

A: The axolotl (Ambystoma mexicanum) is widely used due to its ability to regenerate limbs, spinal cord, and organs.

🔹 Potency in Development

Q: What is the difference between pluripotency and totipotency?

A:

• Totipotent cells (e.g., zygote) can form all cell types, including placenta.

• Pluripotent cells (e.g., embryonic stem cells) can form all cells of the embryo but not placenta.

🔹 Potency in Development

Q: When does totipotency end in a mouse embryo?

A: Totipotency ends at the morula stage (8-cell stage). After that, cells begin to specialize.

🔹 Pluripotency Genes & Reprogramming

Q: What genes maintain pluripotency in embryonic stem cells?

A: Oct4, Sox2, and Nanog.

🔹 Pluripotency Genes & Reprogramming

Q: Can a differentiated cell revert to an embryonic state?

A: Yes. Induced pluripotent stem cells (iPSCs) are made by reprogramming differentiated cells using pluripotency genes like Oct4, Sox2, Klf4, c-Myc.

🔹 Cell Death

Q: What is the difference between necrosis and apoptosis?

A:

• Necrosis: accidental, messy cell death due to damage, causes inflammation.

• Apoptosis: programmed, clean death with no inflammation, membranes stay intact.

🔹 Cell Death

Q: Is apoptosis a normal part of development?

A: Yes. It is essential for sculpting tissues, like digit separation and neural pruning.

🔹 Caspase Cascade

Q: What is the sequence of events involving initiator and executioner caspases?

A:

1. Initiator caspases (e.g., Caspase-8, -9) are activated by apoptotic signals.

2. They cleave and activate executioner caspases (e.g., Caspase-3, -7), which dismantle the cell.

🔹 Caspase Cascade

Q: What does caspase-dependent, CAD do during apoptosis?

A: Caspase-activated DNase (CAD) fragments DNA between nucleosomes, creating a ladder pattern on gel electrophoresis.

🔹 Caspase Cascade

Q: What is the “EAT ME” signal on apoptotic cells?

A: The exposure of phosphatidylserine on the outer leaflet of the plasma membrane, recognized by phagocytes.

🔹 Cancer Progression

Q: What are the steps in transformation toward a malignant phenotype?

A:

1. Hyperplasia

2. Dysplasia

3. In situ carcinoma

4. Invasive carcinoma

5. Metastasis

🔹 Anchorage Dependence & Contact Inhibition

Q: What is anchorage dependence?

A: Normal cells require attachment to ECM to grow and survive; mechanical signals from the matrix regulate proliferation.

🔹 Anchorage Dependence & Contact Inhibition

Q: What is contact inhibition?

A: Normal cells stop dividing when they touch neighboring cells. Tumor cells often ignore this signal and continue dividing.

🔹 Tumor vs. Normal Cells

Q: How do tumor cells differ from normal cells?

A:

• Lose contact inhibition

• Ignore anchorage dependence

• Divide uncontrollably

• Show genomic instability

• Can evade apoptosis

🔹 Tumor vs. Normal Cells

Q: Can cancer cells have abnormal karyotypes?

A: Yes. Many cancers show aneuploidy, translocations, or chromosome amplifications.

🔹 Genetic Alterations

Q: What can point mutations, translocations, or amplifications do?

A:

• Point mutations: activate oncogenes or inactivate tumor suppressors

• Translocations: create fusion proteins (e.g., BCR-ABL in CML)

• Amplifications: overexpress oncogenes (e.g., MYC)

🔹 Multi-Hit Model

Q: What is the multi-hit model of cancer?

A: Cancer develops after multiple genetic alterations accumulate in a single cell lineage over time. Each “hit” affects genes controlling cell growth or survival.

🔹 Checkpoints & p53

Q: What is p53’s role in cancer prevention?

A: p53 is a tumor suppressor that:

• Pauses the cell cycle

• Promotes DNA repair

• Triggers apoptosis if damage is irreparable
  Mutated in >50% of human cancers.

🔹 Viruses and Cancer

Q: How do viruses cause cancer?

A:

• Insert viral oncogenes (e.g., HPV E6/E7 in cervical cancer)

• Disrupt tumor suppressor genes

• Cause chronic inflammation or genomic instability