Adult stem cells Flashcards
Where are embryonic stem cells found?
In the BLASTOCYST
Where are tissue stem cells found?
Fetus, baby and throughout life (adult stem cells)
What potency does the zygote have?
TOTIpotent
What happens to the cells of the blastocyst at the 32-cell stage?
Cells on the OUTSIDE acquire different fates to the cells on the INSIDE
What do the cells on the outside of the blastocyst become?
What does this give rise to?
TROPHECTODERM
Gives rise to the placenta
What do the cells on the inside of the blastocyst do?
What do they become?
- Start to pull away from the trophectoderm and cluster together
Forms:
- The inner cell mass, which forms the embryo
What are ES cells?
EMBRYONIC stem cells:
- Cells of the inner cell mass of the blastocyst stage embryo
What the ES cells do when cultured in a dish?
1) To grow MORE cells (self-renew)
2) Can DIFFERENTIATE into a specialised cell type
What causes the ES cells in culture to differentiate?
Exposure of the cells to an array of factors (known about through study of embryogenesis)
What is the use of ES cells useful for?
What is the use not useful for?
Useful as:
- A TOOL for the study of specific cell populations (for drug screening)
Not useful as:
- REGENERATIVE medicine - ES cells are from NON-host tissue (rejection)
What is a stem cell?
A cell which has ENDLESS RENEWAL - forming a daughter cell that looks exactly like the mother
A cell which can differentiate into multiple lineages/fates to a specialised cell type (HIGH potency)
What forms a progenitor cell?
How is it different to a stem cell?
A stem cell restricting its fate
Different to a stem cell:
- Limited self-renewal
- Limited potency/differentiation
Why is self-renewal of stem cells needed?
To MAINTAIN the stem cell pool (don’t run out)
How do stem cells self-renew?
Every cell division occurs asymmetrically:
- Retains one stem cell
- Forms one specialised cell
Why is differentiation of stem cells needed?
- To REPLACE the dead/damaged cells throughout your lifetime
OR
- To ADD new cells - increasing organ size or generating cell types that are specifically needed at a CERTAIN TIME in life
Describe the balance between self-renewal and differentiation of stem cells
CHANGES throughout lifetime:
In the embryo - LOTS of differentiation
Once body built - Less differentiation
Why does the amount of stem cells decrease from the embyro to the adult body?
- In the embyro - lots of differentiation to build body tissues etc, so need lots of stem cells
- In the adult body - only REGENERATION (less stem cells)
What are adult/tissue specific stem cells?
What do they produce? Why?
- MULTIPOTENT stem cells that are retained in each body tissue in order to maintain the body tissue throughout life
- Produce specialised, differentiated somatic cells (as differentiated cells DO NOT divide) - within their specific cell lineage
What happens to a cell when it is in a differentiated state?
No longer mitotic - G0
How are multipotent adult stem cells protected?
In specialised niches in many organs
What is cellular homeostasis?
The BALANCE between stem cells and differentiated cells
The constant/periodic generation of NEW cells to replace the old, damaged and dying cells
What is the differentiation state of an adult stem cell?
Partially differentiated
What 3 roles do adult stem cells play a role in?
1) Maintaining cell populations
2) Help to heal
3) Role in aging
Describe the balance of cellular homeostasis?
- Every cell lost –> need to gain ONE
BUT, this changes throughout life, eg:
- Growth
- Pregnant females - produce more RBC
What mechanisms that control if ASCs are going to self renew or differentiate similar to?
The control mechanisms that build the embyro
What are 5 types of adult stem cells?
1) Hematopoietic
2) Mesenchymal
3) Epithelial
4) Muscle
5) Neural
Where did the understanding of the stem cell come from?
Studies of hematopoeitic stem cells
Which organism was used to gather most understanding about tissue specific stem cells?
The mouse
What 4 things does the niche do?
1) Protects the stem cell
2) Ensures that the stem cell doesn’t excessively proliferate BUT can proliferate in response to signals
3) Ensures that when the stem cell does proliferate is does so appropriately - maintain one stem cell and give rise to a differentiated cell
4) Mediates the correct balance to get the appropriate amount of self-renewal OR differentiation
What does the stem cell go into a differentiated state via?
Via progression to progenitor cell
What are the differences between different stem cell niches?
They all look different
What are the similarities between different stem cell niches?
Stem cell ANCHORED to via CELL ADHESION molecules to STROMAL SUPPORT cells
What happens in the niche when progenitor cells start to differentiate?
Why is this needed?
FEEDBACK to the stem cell from the stromal cells, when the appropriate numbers have been reached
Tells the stem cell to STOP dividing
How do the adult stem cells know when to respond and divide?
Sense the internal conditions of the body
Respond to physiological signals of the body which are transported in the capillary system and neurons to the support cells
Niches have a specialised portal capillary system and neurons that carry the signals
What cells make up the stem cell niche?
What do these cells do?
1) Stem cell
2) Surrounded by many different cell type (support cells) that interact with the environment to activate and then dampen the activation of the stem cell
- Cells secrete signals that are involved in proliferation vs differentiation vs quiescence
3) Progenitor cells
Where are hematopoeitic stem cells (HSCs) found?
In:
- The bone marrow
- Umbilical cord
- Blood
- Placental tissue
What do the hematopoetic stem cells give rise to?
What parts give rise to what?
ALL the blood cell types in the circulatory system
- Myeloid (gives rise to blood cells)
- Lymphoid (gives rise to immune cells)
What are stromal cells?
Stromal cells are connective tissue cells of any organ
What are the factors secreted by the stromal cells the same as?
The factors that maintain the PGCs in their ‘stemness’ state:
- SCF = stem cell factor
What are the signals that are important in maintaining the niche?
BMP
JAK/STAT
What are BMPs a member of?
The TGF beta superfamily
What do stem cells cycle between in the niche?
A QUIESCENT form and an ACTIVE form
What is the QUIESCENT form of the stem cell?
Unable to self-renew or differentiate
What is the ACTIVE form of a stem cell?
Able to self-renew or differentiate
What cells are muscle fibres built from?
Satellite cells - muscle cell precursors that can self-renew or differentiate
Where do satellite cells sit?
OUTSIDE the muscle fibre
UNDERNEATH the basal lamina
ALONG ALL muscle fibres
What state are satellite cells usually in?
Usually quiescent
What TF marks a self-renewing muscle cell?
Pax7
What TF marks a differentiating myogenic cell?
MyoD
What can the TF markers that are expressed in either a self-renewing muscle cell or a differentiating muscle cell be used to look at?
1) Role of diet (sugar)
2) Role of cell-signalling (Sonic hedgehog)
3) Extracellular matrix remodelling
4) Role of primary cilia
In asymmetric cell division and self-renewal
What is the potency state of mesenchymal stem cells?
VERY multipotent (almost pluripotent)
Where are mesenchymal stem cells found?
In MANY tissues of the body:
- Bone marrow
- Fat
- Cord blood
What do mesenchymal stem cells differentiate into?
- Cartilage cells (chondrocytes)
- Muscle cells (myocytes)
- Fat cells (adipocytes)
- Tendons, ligaments and connective tissue
What are the best understood stem cells?
What do they give rise to?
Epithelial stem cells
Give rise to epithelial cells
What % of cells in the body are epithelial?
80%
What are the epithelial cells responsible for?
Covering the internal and external surfaces of the body (eg. gut and skin)
Why are epithelial cells in constant need of replacement?
They are barriers against pathogens
Have a short life span
Where are neural stem cells found?
In the brain
What is the morphology of a neural stem cell?
Radial glial:
- One end attached to the ventricular zone
- Other - long process
What do radial glial cells give rise to?
Neurons
What are the 3 locations of neural stem cells in the body?
1) SUBVENTRICULAR ZONE
2) SUBGRANULAR ZONE
3) HYPOTHALAMUS
Where is the ‘subventricular zone’?
What do the newly born neurons that come from here do?
Lines the lateral ventricles
Neurons MIGRATE to the OLFACTORY BULB via the rostral migratory stream
What are the neurons from the subventricular zone important in?
Important in animals that use smell largely
Where is the ‘subgranular’ zone?
Part of the dentate gyrus of the hippocampus (involved in memory)
Where is the hypothalamus?
Which neurons does it contribute?
Lines the 3rd ventricle
Contributes neurons that are involved in energy/feeding circuits
What is the thought process behind aging?
Thought that all cells can only undergo a LIMITED number of cell divisions
Thought to DEPLETE the stem cell pool with age