Lecture 26 – Stem Cells, Therapeutic and Reproductive Cloning; Signal Transduction I (intro): Communication Between Cells

Q: What is developmental potential, and in what order does it decrease?

The capacity of a cell to differentiate into different cell types. It decreases in the order: totipotent → pluripotent → multipotent → unipotent.

Q: What types of chromatin modifications lead to open vs. closed chromatin?

Methylation and acetylation lead to open chromatin; demethylation and repressive acetylation lead to closed chromatin.

Q: Why do sperm use protamines instead of histones?

Protamines allow fast reprogramming of the embryo after fertilization by tightly packaging sperm DNA.

Q: How does the egg reprogram sperm chromatin after fertilization?

Glutathione in the egg reduces the disulfide bonds joining protamines, uncoiling the sperm chromatin. Protamines are then replaced by histones, followed by histone acetylation and DNA demethylation.

Q: Why is a reprogramming step required after fertilization?

Because both the egg and sperm are differentiated cells, so reprogramming is needed to restore the zygote to a totipotent state.

Q: What is cellular plasticity?

The ability of a partially differentiated adult stem cell to change its genetic program and differentiate into cells of another tissue type.

Q: What evidence supports the idea that the microenvironment can reprogram cells?

Bone marrow cells expressing GFP were injected into a recipient mouse and became functioning Purkinje (brain) cells, suggesting the brain microenvironment reprogrammed their identity.

Q: What are induced pluripotent stem cells (iPSCs)?

Differentiated cells (e.g., skin cells) that have been reprogrammed into pluripotent stem cells by overexpressing four genes normally associated with embryonic stem cells.

Q: What is the significance of human–pig chimera experiments?

Human cells were able to specialize into different tissues within pig embryos kept alive for 28 days, suggesting a potential method for generating humanized organs for donation.

Q: What is the difference between therapeutic and reproductive cloning?

Both use a blastocyst. Therapeutic cloning generates cells for study; reproductive cloning produces a baby organism.

Q: Can the tissue microenvironment reprogram differentiated cells?

Yes — both the egg and the tissue microenvironment are capable of reprogramming the differentiated state of chromatin.

Q: What is signal transduction?

The process by which information from extracellular molecules is translated into an internal cellular signal.

Q: What are the four types of cell signalling based on ligand–receptor proximity?

Juxtacrine (both membrane-bound, cells must touch), autocrine (cell signals itself), paracrine (signal reaches a neighbouring cell), and endocrine (signal travels through the bloodstream).

Q: What characterizes G protein-coupled receptors (GPCRs)?

They are transmembrane proteins connected to G proteins on the inside of the cell. They activate signal pathways through enzymes that often produce second messengers to amplify signals.

Q: How do receptor tyrosine kinases function?

They have a built-in kinase domain that phosphorylates tyrosine amino acids upon ligand binding, initiating a signal transduction pathway.

Q: How do cytokine receptors differ from receptor tyrosine kinases?

Cytokine receptors lack their own kinase function. They associate with Jak kinases, which provide the phosphorylation ability.

Q: What are nuclear hormone receptors, and how do they work?

They are cytosolic receptors that bind hydrophobic ligands (e.g., estrogen, testosterone) that pass through the membrane. The ligand–receptor complex then acts as a transcription factor.

Q: What are the main categories of extracellular messengers?

Amino acid derivatives (e.g., ACh, adrenaline), gases (NO, CO), steroids from cholesterol (e.g., estrogen, testosterone), eicosanoids from arachidonic acid, and peptides/proteins (the largest group).

Q: What are second messengers?

Non-protein molecules produced inside the cell that amplify the signal initiated by the first messenger (the ligand).

Q: How does reversible phosphorylation regulate signal transduction?

Protein kinases transfer a phosphoryl group from ATP to a substrate protein to activate it. Protein phosphatases remove the phosphoryl group to inactivate it. Dephosphorylation can occur at any point.

Q: Which amino acids can be phosphorylated by kinases?

Serine (Ser), threonine (Thr), tyrosine (Tyr), histidine (His), and arginine (Arg).

Q: What factors control signal transduction specificity?

Cell type-specific expression of ligand-specific receptors, timing of docking protein activation, presence or absence of docking sites, and inhibitory proteins that limit signalling duration.

Q: Describe the prolactin–Jak–STAT signalling pathway.

Prolactin binds its cytokine receptor → two receptor chains dimerize → conformational change → Jak2 kinase is activated → phosphorylation cascade reaches STAT molecules → STAT acts as both a transducer and transcription factor to promote gene expression (e.g., casein/milk protein).

Q: What does Jak2 stand for, and what are its two roles?

Janus kinase 2 (also called “just another kinase”). One role: activating the receptor and creating docking sites for STAT. Other role: transducing the signal.

Q: What is the function of STAT’s SH2 domain?

The SH2 domain allows STAT to bind phosphorylated proteins, enabling it to be recruited to the activated receptor and participate in signal transduction.