The Birth and Death of Cells

Stem Cell Characteristics

• A cell that has the ability to continuously

divide and differentiate (develop) into various
other kind(s) of cells/tissues
Stem Cells
• Blank cells’
(unspecialized)

• ability to reproduce
themselves indefinitely
(self-renewal)

• ability to divide
asymmetrically to give
rise to specialized cell
types (differentiation)
 Kinds of Stem Cells

Stem cell
type Description Examples
Cells from early
Each cell can develop
Totipotent (1-3 days)
into a new individual
embryos
Some cells of
Cells can form any (over
Pluripotent blastocyst (5 to 14
200) cell types
days)
Cells differentiated, but Fetal tissue, cord
Multipotent can form a number of blood, and adult
other tissues stem cells
 This cell
Can form the
Embryo and placenta

This cell
Can just form the
embryo

Fully mature
Unipotent
Symmetric cell division
Asymmetric cell division
1. Self-renews
2. Differentiates

Progenitor cell

Stem cell Stem cell

 SELF – RENEWAL 
Tissues Are Maintained by Associated
Populations of Stem Cells
Skin
Blood Cells
Intestine
Cell Death and Its Regulation
 OPTIMAL FUNCTION (HEALTH)

APOPTOSIS

AGING

APOPTOSIS
Neurodegeneration, cancer, …..
Cell Death
• Cell death by injury
 Mechanical damage
 Exposure to toxic chemicals
• Programmed Cell Death
 Internal & External signals
Programmed Cell Death
• “dropping off” or “falling off

• Apoptosis or programmed cell death, is carefully coordinated collapse

of cell, protein degradation , DNA fragmentation followed by rapid
engulfment of corpses by neighbouring cells. (Tommi, 2002)

• Odd cell fate but Essential part of life for every multicellular organism
from worms to humans
Why should a cell commit suicide?
Apoptosis is needed for proper development
Examples:
• The resorption of the tadpole tail
• The formation of the fingers and toes of the fetus
• The sloughing off of the inner lining of the uterus
• The formation of the proper connections between neurons in the brain

Apoptosis is needed to destroy cells

Examples:
• Cells infected with viruses
• Cells of the immune system
• Cells with DNA damage
• Cancer cells
What makes a cell decide to commit suicide?

Withdrawal of positive signals

examples :
• growth factors for neurons
• Interleukin-2 (IL-2)

Receipt of negative signals

examples :
• increased levels of oxidants within the cell
• damage to DNA by oxidants
• death activators :
• Tumor necrosis factor alpha (TNF-)
• Lymphotoxin (TNF-β)
• Fas ligand (FasL)
NECROSIS Vs APOPTOSIS

Wilde, 1999
Necrosis vs. Apoptosis
Necrosis Apoptosis
• Cellular swelling • Cellular condensation
• Membranes are broken • Membranes remain intact
• ATP is depleted • Requires ATP
• Cell lyses, eliciting an • Cell is phagocytosed, no tissue
inflammatory reaction reaction
• DNA fragmentation is • Ladder-like DNA fragmentation
random, or smeared • In vivo, individual cells appear
• In vivo, whole areas of affected
the tissue are affected
Stages of Apoptosis
 Pathways of Apoptosis
“Extrinsic Pathway”

Death Death Initiator

Ligands Receptors Caspase 8

Effector
“Intrinsic Pathway”
Caspase 3 PCD

DNA Initiator
Mitochondria/
damage Caspase 9
Cytochrome C
& p53
 “Intrinsic Pathway”

• Intracellular stresses
• DNA damage
• Hypoxia
• Energy depletion
• Growth factor withdrawl
A Cascade of Caspase Proteins
Functions in One Apoptotic Pathway
Regulators-Bcl-2 family
Proapoptotic
(red)
Antiapoptotic
(Green)
Adaptor

Apaf1
Effectors-Caspases
attack key cysteine residue in the catalytic site and selectively cleave
proteins at sites just C-terminal to aspartate residues.
 Pathways of Apoptosis
“Extrinsic Pathway”

Death Death Initiator

Ligands Receptors Caspase 8

Effector
“Intrinsic Pathway”
Caspase 3 PCD

DNA Initiator
Mitochondria/
damage Caspase 9
Cytochrome C
& p53
Extrinsic Pathway
Ligand-induced cell death

“The death receptors”

FasL Ligand-induced trimerization

Trail
TNF

Death Domains

Death Effectors
Induced proximity
of Caspase 8
Activation of
Caspase 8
Ligand-induced cell death
Ligand Receptor
FasL Fas (CD95)activated natural killer cells and cytotoxic T
lymphocytes
TNF TNF-R macrophages
TRAIL DR4 (Trail-R)
Ligand-induced cell death

“The death receptors”

FasL Ligand-induced trimerization

Trail
TNF

Death Domains

Death Effectors
Induced proximity
of Caspase 8
Activation of
Caspase 8