L16: Stem cells Flashcards
what is a stem cell key properties?
Self-Renewal:
Stem cells preserve themselves in an undifferentiated state, ensuring the stem cell pool is maintained. This occurs within the stem cell niche in adult organs.
Differentiation Potential:
Upon leaving the niche, stem cells can differentiate into specialized cell types. This differentiation can occur at different levels of specialization, from partially differentiated cells to fully specialized ones.
hirearchy of cell potency?
totipotent: (omnipotent) five rise to any of the 220 cell types found in embryo as well as extra-embryonic cells (placenta)
pluripotent stem cells: give rise to all cell types of the body but not extra-embryonic/placenta
multipotent: develop into a limited number of cell types in a particular lineage e.g: haemapoetic stem cells
unipotent precurosr cells: tissue resident progenitor/stem cells, capacity to give rise to one cell type only.
stem cell potency?
Totipotent (Pre-implantation Embryo):
A fertilized egg (zygote) and the embryo at the morula stage are totipotent, meaning they have the potential to differentiate into any cell type, including both embryonic and extra-embryonic tissues (e.g., placenta).
Pluripotent (Inner Cell Mass of Blastocyst):
The inner cell mass of the blastocyst (pre-implantation) is pluripotent. These cells can differentiate into any of the three germ layers (ectoderm, mesoderm, and endoderm), but not extra-embryonic tissues.
Multipotent and Unipotent (During Development/Adult):
In different organs or tissues, stem cells become multipotent (can differentiate into a limited range of cell types) or unipotent (can differentiate into only one type of cell).
Examples of multipotent stem cells:
Circulatory system: Hematopoietic stem cells (blood cells)
Nervous system: Neural stem cells
Immune system: Hematopoietic stem cells (immune cells)
what are the different types of stem cells?
embryonic stem cells: originate from inner cell mass of blastocyst, self-renewal, pluripotent, generation of mouse chimeras, generation of 254 cell types originating adult tissues. give rise to cells from all 3 embryonic germ layers e.g: ectoderm such as neurons, mesoderm: blood cells, endoderm e.g: liver cell.
adult stem cells: created during ontogeny and persist within the niche in most adult animal tissues/organs, self renewal, multipotent, maintenance of tissue homeostasis in physiological and pathological conditions.
induced pluripotent stem cells: originate from somatic differentiated cells after transduction oct4, myc, dox2, klf4. The transcriptional program and epigenetic memory of the original somatic cell are “erased” during this process. Essentially, the cell undergoes epigenetic reprogramming, resetting it to a pluripotent state, similar to that of an embryonic stem cell.self renewal. pluripotent, gen of mouse chimeras, patient-specific stem cells
intrinsic and extrinsic factors in pluripotency in establishing cell identity?
Intrinsic Factors:
These are transcription factors and epigenetic regulators that play a crucial role in maintaining pluripotency and self-renewal. Key transcription factors like Oct4 and Nanog are essential for preserving the pluripotent state of stem cells.
Extrinsic Factors:
These include soluble signaling molecules released by the surrounding tissue. In the case of mouse embryonic stem cells (mESCs), the LIF (Leukemia Inhibitory Factor) growth factor is important for maintaining pluripotency and self-renewal.
For human ESCs (hESCs), the key extrinsic factors are FGF (Fibroblast Growth Factor) and Activin signaling pathways, which help sustain pluripotency.
mouse vs human embryonic stem cells?
mEpiSC vs hESC:
Similarities:
Both mEpiSCs (mouse epiblast stem cells) and hESCs (human embryonic stem cells) are derived from the inner cell mass (ICM) of the blastocyst during early development.
Differences:
Morphology: The colonies of mEpiSCs and hESCs differ in appearance.
Extrinsic Factors: The growth factors used to culture and maintain pluripotency differ:
Mouse ESCs require LIF.
Human ESCs require FGF and Activin signaling.
Developmental Stage Differences:
Mouse ESCs: These cells are naive, representing the ground state of pluripotency. They are derived from the true blastocyst stage.
Human ESCs: These cells are considered primed and more prone to differentiation. They are derived from a late blastocyst stage—specifically, the epiblast, which is a more advanced stage of development.
Mouse ESCs are difficult to differentiate in culture because they are in the naive state, requiring additional signals to induce differentiation.
Human ESCs are already in a primed state, which means they are more likely to differentiate, making it easier to promote differentiation under the right conditions.
what are induced pluripotent stem cells and what are their applications?
Mature, diff cells can be reprogrammed to become pluripitent.
Soamtic cells oct4, sox2, c-myc, klf4—-> ips cells
Become neurons, cardiomyocytes, hepatic cells, pancreatic cells.
Breakthrough: study of development, pathogenic study, stem-cell based regen
Application- e.g: disease modelling
adult stem cells?
After birth, adult stem cells are generally multipotent or unipotent with restricted plasticity/potency. They remain in an undifferentiated state and are found in specific tissues or organs that require continuous self-renewal. These cells can differentiate to produce some or all of the specialized cell types of their respective tissue or organ.
Key characteristics of adult stem cells:
Limited quantities and often difficult to identify.
Common in tissues/areas with constant turnover or self-renewal, such as blood and the intestine.
For example:
Hematopoietic stem cells (HSCs) are found in a niche within the bone marrow, where they self-renew and differentiate into all blood and immune cell types.
HSCs produce around 10^11 to 10^12 new blood cells daily.
Adult stem cell niches:
Cellular niches: Where adult stem cells interact with supporting cells (e.g., bone marrow and intestine).
Non-cellular niches: Composed of extracellular matrix (ECM), such as in muscles where satellite cells remain in the basal lamina to maintain an undifferentiated state.
the stem cell niche?
Skin: Like blood, the skin has high turnover. Epidermal stem cells reside in hair follicles, surrounded by a complex niche.
Intestinal Stem Cells: The intestinal epithelium requires constant turnover, with cells being replaced every 5 days. A dedicated pool of adult stem cells is essential for this process.
Location: Intestinal stem cells reside at the bottom of the crypts, surrounded by supporting Paneth cells, which help maintain their undifferentiated state.
Response to Cell Loss: When cells of the villi are lost, the stem cell pool is activated. The adult stem cells mobilize, re-enter the cell cycle, amplify, and move along the villi. As they move, they acquire differentiated states and contribute to the various intestinal cell types.
Turnover Process: The cells continue to move upward, eventually shedding from the top of the villi, and the process repeats.
Small Intestinal Epithelium: Has an extremely short turnover time of 5 days.
Lgr5+ Intestinal Stem Cells: These stem cells are involved in sensing signals that trigger the stem cell pool’s activation. Their activity has enabled scientists to establish intestinal organoids in research.
stem cell niche types?
Cellular Niche:
Composed of supporting cells that help maintain stem cell self-renewal.
Regulates proliferation and directs subsequent differentiation of stem cells.
Non-Cellular Niche:
Made up of the extracellular matrix (ECM) and secreted signals.
Supports stem cell self-renewal.
Regulates proliferation and differentiation of stem cells.
