Stem Cells Flashcards
What are stem cells?
A stem cell is the most immature cell type
What are the 3 key features of stem cells?
- They have the ability to self-renew and replace themselves.
- Stem cells are the only cell type that have the potential to differentiate into any cell type (multi-potent).
- They can enter quiescence when not needed (reversible step in cell cycle - G0).
What are the 2 different ways stem cells can undergo self-renewal?
A stem cell can divide in two ways:
- Asymmetrically: Produces one identical copy of the parent cell and one slightly differentiated progenitor cell.
- Symmetrically: Produces two stem cells identical to the parent cell.
What form are stem cells normally in?
Stem cells only function when they are needed and are mostly in a quiescent state, waiting for an external signal to divide.
What is the importance of quiescence?
Quiescence reduces the number of divisions to protect the genome from DNA damage.
How are stem cells capable of mass cell production?
They go through a stage known as transit amplifying cells, replicating transiently to avoid compromising the stem cell population.
Define potency.
Potency refers to how many cell types a stem cell can give rise to.
What does the potency of a stem cell depend on?
The potency of a stem cell depends on its origin.
What are the 4 levels of potency?
- Totipotent: Can differentiate into any and all cell types.
- Pluripotent: Can differentiate into all cell types of the embryo but not into an entire organism.
- Multipotent: Can differentiate into 2 or more cell types within a specific tissue.
- Unipotent: Can only differentiate into a single cell type.
What happens to potency as the embryo grows?
As the embryo develops, stem cells lose potency and can only differentiate into specific tissue lineages.
What is the potency of a zygote?
The zygote is totipotent and can give rise to every cell type.
When does the zygote become pluripotent?
The zygote becomes pluripotent after the 8-cell stage.
What is the potency of adult stem cells?
Adult stem cells are multipotent.
Where are embryonic stem cells derived from?
Embryonic stem cells are derived from the inner cell mass of the blastocyst.
Define stem cell niche.
The stem cell niche is the tissue or organ where the stem cell is present, and its growth is dependent on this niche.
What do stem cells require to maintain themselves?
Stem cells require signals from a specialized niche that provides necessary signals for maintenance.
What governs the concentration gradient of signals in the external environment of stem cells?
The extracellular matrix governs the concentration gradient of extracellular signals that stem cells are sensitive to.
What are the differences between adult and embryonic stem cells?
Embryonic stem cells are derived from early embryos and have more potential than adult stem cells, which arise in the fetus and maintain organs throughout life.
What are the challenges of adult stem cells?
- Stem cells are rare.
- Cells within adult tissue are heterogeneous.
- Some adult tissues are inaccessible for isolation.
- Removal from the niche can change stem cell properties.
- Stem cell number limits applications.
- Not all tissue stem cells are well characterized.
What are the limitations to allogeneic bone marrow stem cells?
We cannot force people to donate their bone marrow, necessitating the need to find ways to make stem cells in vitro.
What causes sickle cell disease and what is the only cure?
Sickle cell disease is caused by a homozygous single point mutation in HBB, and the only cure is a stem cell transplant.
How does hemoglobin switch during development?
Hb switches from embryonic to fetal Hb as the gamma globin gene is switched on, and at birth, the gamma globin gene is switched off while the beta globin gene is switched on.
How can sickle cell disease be corrected?
- Fix the point mutation using CRISPR Cas9.
- Keep fetal hemoglobin in adult cells by targeting protein BCL11A.
What is a downside of CRISPR?
The cost is approximately $2 million per patient.
What is a promising solution for culturing stem cells?
The use of pluripotent stem cells is a promising solution.
Where can pluripotent stem cells be derived from?
- From embryos (pre-implantation blastocyst).
- By inducing pluripotency (iPS).
What factors are essential in the maintenance of the pluripotent phenotype?
- Sox2
- Oct4
- Nanog
LIF and BMP inhibit differentiation.
How could embryonic stem cells transform medicine in the future?
Embryonic stem cells have the potential to address various medical conditions and improve regenerative medicine.
How could ES cells transform medicine in the future?
Describe therapeutic cloning.
Therapeutic cloning involves the transfer of a somatic cell nucleus into an empty oocyte, and then triggering cell division. The inner cell mass is then removed at the blastocyst stage and can then be cultured to make specific cells. These ES cells are derived from the patient’s own somatic cells, and therefore they will not be rejected by the host’s immune system, should they be transplanted back into the patient. However, the problem with this technique is that it requires the removal of eggs from young women.
What are the ethical considerations of therapeutic cloning?
You have to destroy an embryo (creating a life to destroy it) and there is a risk of teratomas (tumour made up of all germ cells).
What are induced pluripotent stem (iPS) cells?
Induced pluripotent stem (iPS) cells are stem cells that have been derived directly from differentiated cells. This reversal of the differentiation process is achieved via the transfection of fibroblasts with a combination of pluripotency inducing transcription factors (e.g. Oct4, Sox2, Klf4, cMyc), leading to the formation of ES-like cells. These ES cells can then be pushed down other cell lines through further transcription factor transfection. The aim of iPS is to reverse the epigenetic processing that has occurred within a differentiated cell, to create a pluripotent cell.
Describe the process of normal germ cell differentiation.
What is the process of using iPS cell-derived oocytes to produce offspring in mice?
Describe in-vitro gametogenesis (IVG) from a single parent. What are the genetic implications?
Recessive conditions (e.g., CF) will be passed on to the offspring, ultimately leading to inbreeding.
What is iPS therapy for diabetes?
Basically correct beta cells in pancreas (type 1).
