7- stem cells Flashcards
stem cells
Undifferentiated cells capable of self-renewal and differentiation into specialised cell types.
totipotent stem cells
• Can give rise to all cell types of the body as well as the extra-embryonic placental cells.
• e.g. Early embryonic stage: Cells in the early embryonic stage (fertilised egg, zygote, cells produced by the first few divisions) are totipotent.
pluripotent stem cells
• Can give rise to all cell types of the body but not the extra-embryonic placental cells.
• e.g. Embryonic stem cells: Cells derived from the ICM of the embryo are pluripotent.
• e.g. Induced pluripotent stem cells (iPSCs): These are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state, exhibiting pluripotency.
multipotent stem cells
• They can differentiate into a limited number of cell types within a particular lineage.
• e.g. Adult stem cells: Found in various tissues in the body (like bone marrow, skin, or gut), these stem cells are generally multipotent and give rise to the various cell types of the tissue in which they reside.
importance of stem cells
• Play crucial roles in development and tissue regeneration.
• Potentially useful in therapeutic applications such as regenerative medicine and drug discovery.
pluripotent stem cells and medical advances
• Disease modelling → Pluripotent stem cells can be used to create disease models in a dish, allowing researchers to study disease mechanisms and test potential treatments.
• Drug testing → These cells can be used to test the safety and effectiveness of new drugs before they are tested in humans.
• Regenerative medicine → They offer potential in the field of regenerative medicine, where they could be used to generate replacement tissues or organs for transplantation.
ethical considerations of stem cells
• Source of embryonic stem cells: Cells are typically taken from surplus embryos from IVF clinics. The destruction of these embryos to obtain stem cells raises ethical concerns.
• Consent: There are issues surrounding informed consent from donors of the original embryos.
• Potential for exploitation: Potential for exploitation or coercion in the procurement of embryos.
• Cloning and genetic modification: The use of techniques like CRISPR for creating or modifying embryonic stem cells raises ethical and safety concerns.
totipotent to pluripotent transition
• In the early embryo, cells are totipotent and can develop into any cell type, including extra-embryonic tissues. As the embryo develops into a blastocyst, epigenetic changes occur that limit the potential of the cells in the inner cell mass, making them pluripotent.
DNA methylation in stem cells
The patterns of DNA methylation change dynamically during this transition. Totipotent cells show a relatively low level of methylation which increases as cells become pluripotent.
histone modifications in stem cells
Changes in histone modifications also play a role, with specific patterns associated with totipotent and pluripotent states.
pluripotent to somatic cell differentiation
As the embryo continues to develop, pluripotent stem cells in the ICM begin to differentiate into the somatic cell types that make up the different tissues of the body.
lineage- specific gene expression
Epigenetic modifications, including
DNA methylation and histone modifications, help to turn off pluripotency genes and turn on genes specific to each cell lineage, guiding the cells along their path to differentiation.
maintaining cell identity
Once a cell has differentiated, further epigenetic modifications help to lock in the cell’s identity, stably repressing genes associated with other cell types while keeping the necessary genes active.
reprogramming of differentiated cells
Differentiated cells, such as fibroblasts, can be reprogrammed back into a pluripotent state to form induced pluripotent stem cells (iPSCs). This reprogramming process involves artificially introducing specific genes that are usually active in pluripotent cells.
key genes involved in reprogramming of differentiated cells
Yamanaka factors: The crucial genes typically used for reprogramming are Oct4, Sox2, Klf4, and c-Myc (collectively known as Yamanaka factors).
how iPSCs are introduced
The Yamanaka factors are typically introduced into the fibroblasts using viral vectors, although other methods such as plasmid transfection can also be used.
formation of iPSCs
Once inside the cells, the Yamanaka factors activate the transcription of genes associated with pluripotency, resetting the cells’ identity and turning them into iPSCs.
epigenetic reprogramming- iPSCs
The process of forming iPSCs involves substantial changes to the cells’ epigenetic state, including changes in DNA methylation and histone modification, to resemble that of embryonic stem cells.
re-acquiring pluripotency- iPSCs
iPSCs regain the ability to differentiate into any cell type in the body, much like embryonic stem cells.
Why iPSCs may be less problematic than embryonic stem cells
• Ethical considerations: Unlike embryonic stem cells, which are derived from embryos (raising ethical concerns about the destruction of potential human life), iPSCs are generated from adult cells, avoiding these ethical dilemmas.
• Source of cells: iPSCs can be generated from a patient’s own cells, reducing the risk of immune rejection in therapeutic applications compared to embryonic stem cells which are obtained from donors.
• Consent and availability: The procurement of adult cells to generate iPSCs is generally less contentious and easier than obtaining embryonic stem cells, which require informed consent from embryo donors.
challenges with iPSCs
• Safety and quality control: The use of viral vectors to introduce pluripotency genes can potentially cause mutations.
Additionally, the reprogramming process can sometimes be incomplete, leading to variability in the quality and characteristics of iPSCs.
• Efficiency: The process of generating iPSCs is currently still inefficient and time-consuming.
