Chapter 8: Stem cells and differentiation (Lecture, main) Flashcards
What are the different subjects that will be discussed in the lecture? (you obv don’t have to learn this)
- Stem cells and differentiation
- Epigenetic mechanisms regulating self-renewal and differentiation
- Different kind of stem cells and how to make them
- Cancer cells with self-renewal capacity: cancer stem cells
- Leukemia and leukemic stem cells
- Self-renewal signaling pathways: Notch, Wnt and Hedgehog
- The polycomb pathway
- Lineage specific transcription factors
What are the two characteristics of a stem cell?
- Ability to divide (self replicate) for indefinite periods throughout the life of an organism (self renewal)
- Ability to differentiate to the many different cell types upon different signals (pluripotency)
How is the process called whereby stem cells become specialized to perform a particular function
Differentiation
In what two ways can a stem cell divide?
Symmetrical (copy) and asymmetrical (differentiation)
What are the different types of stem cells and their characteristics?
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Totipotent Stem Cell: the potential to create any type of cell necessary for embryonic development
- (extraembryonic membranes and tissues, the embryo itself, and all postembryonic tissues and organs).
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Pluripotent Stem Cell (PSC): the capability of developing cells of all germ layers
- (endoderm, ectoderm, and mesoderm).
- Multipotent Stem Cell: give rise to cells that have a function dependent of the embryonic germ layer they derived from.
Which cells are in heterochromatin, and which are in euchromatin form: stem cells or differentiated cells?
- Heterochromatin: differentiated cells (‘closed’ structure)
- Euchromatin: stem cells (‘open’ structure)
Stem cells can also be divided into embryonic stem cells and adult stem cells. Can you explain what they mean?
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Embryonic stem cells – they are pluripotent – indefinite self-renewal
- Embryonic stem cells of the inner cell mass are able to differentiate to generate primitive ectoderm which differentiate during gastrulation into endoderm, ectoderm and mesoderm
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Adult stem cells – they are multipotent – limited self-renewal
- They are present in every tissue and involved in regeneration of these tissues.
- Examples: hematopoietic stem cells (in the bone marrow), hair follicle stem cells, breast stem cells and intestinal stem cells
There are many different strategies for stem cell therapy but what are the three types that will be discussed?
- Embryonic stem (ES) cells
- Induced pluripotent stem (iPS) cells
- Nuclear transfer embryonic stem (NT-ES) cells
How are embryonic stem (ES) cells ‘made’?
Embryonic stem cells are derived from inner cell mass (from embryo’s)
How are induced pluripotent stem (iPS) cells ‘made’?
They are induced, by adding repogragramming factors (Yamanaka factors) to mature differentiated cells, so they become pluripotent stem cells
How are nuclear transfer embryonic stem (NT-ES) cells ‘made’?
This was how Dolly was made, a cytoplasmic donor with enucleated cell/oocyte and a somatic nuclear donor cell is needed. After the cell and the DNA are ‘merged’, it is injected in a third animal that will carry the blastocyst.
In the cell, there is a balance between self-renewal and differentiation. What happens when the cell is in balance?
There is tissue homeostasis, a.k.a. normal tissue
In the cell, there is a balance between self-renewal and differentiation. What happens when the cell is shifted towards differentiation?
There is tissue aging and/or degeneration
In the cell, there is a balance between self-renewal and differentiation. What happens when the cell is shifted towards self-renewal?
Cancer.
For an overview of the different ‘balances’, see this figure
So, tumor cells are associated with self-renewal. In what ways can they acquire self-renewal?
- Aberrant expression of (mutated) genes induce stem cell features
- The initial/founder hit (driver mutation) is in a stem cell. Tumor has inherited the stem cell state/features of the cell of origin
- Microenvironment imposes stem cell features onto the cancer cells
What is the evidence that suggests that stem cells are the origin of cancer? (+ can you also name examples?)
- Self-renewal-long life of normal stem cells offers opportunities for mutations and thereby for cancer formation (Example: skin).
- More differentiated normal cells obtain self-renewal capacity (mutation) (example: acute and chronic myeloid leukemia and colon cancer): “De novo stem cells”
There is additional evidence for stem cell origin of tumors… what are they?
(besides:
- Self-renewal-long life of normal stem cells offers opportunities for mutations and thereby for cancer formation.
- More differentiated normal cells obtain self-renewal capacity (mutation) “De novo stem cells”)
- Tumor specific mutations are present in the normal stem cell compartment (Example for leukemia)
- Presence of similar cell surface markers in normal- and cancer stem cells
Earlier, we noticed that tumor specific mutations that are present in the normal stem cell compartment are additional evidence that stem cells are the origin of tumors. How is this phenomenon called and how does it ‘work’?
Clonal hematopoiesis (CHIP): aging related phenomenon in which hematopoietic stem cells (HSCs) contribute to the formation of a genetically distinct subpopulation of blood cells (example: acute and chronic myeloid leukemia)
Earlier, we noticed that the presence of similar cell surface markers in normal and cancer stem cells is evidence that stem cells are the origin of cancer. What are some examples of diseases where these markers can be used?
Examples are AML, CML and brain tumors, but as you can see in this figure there are many more