Week 2 Flashcards
Stem cell niche:contact and communication with stem cells (come back)
- Direct cell -cell interactions ( organizing cells,for example, hub cells are found in the stem cell niche to support stem cells and regulate them via signals)
- indirect cell-cell interactions( fibroblasts=
What is pattern formation?
Describes the events that determine spatial organization in an embryo and includes molecules that signal whether a target cell is head or tail or dorsal or ventral
What are morphogens?
- Pattern formation molecules/signalling molecules that are present in a concentration gradient in a region
- cells obtain spatial information from the gradients so they can know where they should migrate to
-genes activated by morphogens generate signals that provide more specific information about cell location
Discovery of the Bicoid morphogen
-exposed fruit flies to mutagens
-pattern formation mutants had defects in the body plan
-bicoid was one that was found to affect the anterior-posterior axis
-bicoid was found to encode a morphogen because when a mutant fruit fly did not express bicoid, the fly only had posterior structures on both ends of the embryo with no anterior structure
In situ hybridization
- used to find out what happens in mutants and where a specific mRNA is located
- Steps:
1. get a single stranded DNA or RNA that is complimentary to the target mRNA (in this case, target =bicoid)
2. Label with fluorescence
3. Allow the probe/complimentary strand to hybridize to its complimentary sequence (target) by adding many copies (PCR amplification) to preserved embryo cells of. the organism
4. wash away any unbound RNA
5. Fluorescence shows where the target mRNA is located in the embryo
Conclusions made by In situ hybridizatioj for bicoid
- morphogens work in a gradient and bicoid dictates whether anterior or posterior structures will be formed in regions of the embryo
- bicoid was found to be a regulatory transcription factor and it binds to enhancers and activates genes that form anterior structures
- higher concentrations = anterior end; lower concentrations = posterior end
- in fruit fly embryo, bicoid exists in a decreased concentration towards the embryos posterior and so there’s different genes in both ends of the embryo
What is Wnt
- wingless-related integration site
- highly conserved in vertebrates and is a form of communication with stem cell and its niche
pathway:
- binding of wnt proteins to their receptors maintains stem cells and other functions depending on where they are located
- initiates stem cell renewal in intestinal and hematopoietic tissue (=symmetric division/stem cell expansion)
- initiates differentiation in other stem cell types
what links stems cells to niche and supporting cells and ECM?
- cadherins and integrins
-integrins = controls adhesion between stem cells to ECM - cadherins = controls adhesion between cells (for example, between stem cells and supporting cells)
stem cell niche and aging
- one reason that causes aging is that there is a gradual loss of stem cell capability
- tissue aging can also be a consequence of a combination of 3 factors:
1. decline in specific stem cells
2. decline in the niche leading to decreased stem cell capacity = aging niche leads to aging stem cells leads to overall aging)
3. decline in the tissue l/whole organism causing compromised niche (aging) and compromised stem cells (aging) - 1 and 2 are intrinsic factors of aging because they occur inside the niche
- 3 is an extrinsic factor of aging because the parts outside of the niche are aging. which causes a decline in communication with the niche for example, with signalling molecules
example of stem cell niche and aging (intrinsic example)
- in fruit fly gonads, hub cells (organizing cells) decline in the testes with aging
- This decline within the niche causes a decline in communication with stem cells
- this leads to decline in sperm
What is the end replication problem?
- a single stranded DNA is left at the end of the lagging strand during replication/ overhang
- This would eventually get degraded which would shorten chromosomes each time they are replicated which would eventually lead to them being eliminated
- ## telomeres don’t contain genes and they are short, repeated bases of DNA and they are found at the end of chromosomes so that when chromosome shortening would occur after DNA replication, only this would be shortened and the coding regions would be protected
how does telomerase synthesize telomeres?
- telomerase has a preference for attaching 6 nucleotides at a time
process:
1. during replication, 3” end of lagging strand forms a single stranded overhang
2. telomerase binds to the overhand and uses its own RNA template to extend the strand by adding additional repeats
3. This creates double stranded DNA to prevent chromosome shortening
how do telomere regions affect stem cells and intrinsic aging?
- somatic cells lack telomerase and so they progressively shorten with replication and age
- telomerase expression is found in reproductive organs and stem cells and is high during embryonic development (due to lots of cell division) but is downregulated a few weeks after birth
- telomere shortening due to aging results in decreased mobilization of stem cells which can cause stem cell apoptosis or senescence (cells stop dividing)
- majority of stem cells don’t have telomerase activity but some do and it’s usually found in stem cells with rapid regeneration like hematopoietic but it can be found in some with low recreation
How is declined muscle mass and declined regenerative capacity associated with aging? (Come back)
-decreased integrin beta 1 expression on muscle satellite cells lead to weaker interaction with ECM since integrins are responsible for cell interaction with ECM
-also leads to their impaired response to growth factors
-ECM components are not upregulated and this can’t be reversed therefore tissue aging occurs
A method for targetting stem cell niche for therapeutics (come back)
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What are the three possible fates of a stem cell?
- Quiescence – Stem cell remains inactive but can be reactivated.
- Cell Division – Can be symmetric (producing identical stem cells) or asymmetric (producing a stem cell + progenitor cell).
- Apoptosis/Senescence – Cell undergoes programmed cell death due to aging or damage.
What is the difference between symmetric and asymmetric cell division?
Symmetric division: Produces two identical stem cells (stem cell expansion).
Asymmetric division: Produces one stem cell and one progenitor cell (stem cell depletion).
What is quiescence in stem cells?
A reversible inactive state where the stem cell does not divide but remains available for future activation.
What leads to stem cell depletion?
Asymmetric division, where one daughter cell differentiates into a progenitor cell, leading to a reduction in the stem cell population.
What is the function of progenitor cells?
Progenitor cells arise from stem cells and are committed to differentiating into specific cell types, but they have limited self-renewal capacity.
What are the key components of the stem cell niche?
- Extracellular matrix
- Signaling molecules (growth factors, cytokines)
- Supporting non-stem cells
- Physical and chemical cues regulating stem cell function.
What did Brian Lord and Mike Dexter’s experiment reveal about hematopoietic stem cells (HSC)?
HSCs retained their potential only when cultured with non-hematopoietic bone marrow stromal cells, showing the importance of the niche.
What was the hypothesis about the stem cell niche?
Schofield proposed that the niche is responsible for maintaining ‘stemness’ by preventing excessive proliferation of stem cells.
What determines whether a stem cell undergoes symmetric or asymmetric division?
The orientation of the stem cell in its niche and local signaling influences the type of division.
What are Hub Cells, and where are they found?
Hub Cells are compact cells that secrete signals and express adhesion molecules to maintain surrounding stem cells.
They are found in Drosophila (fruit flies).
What are Organizer Cells, and where are they found?
Organizer Cells instruct the fate and morphogenesis of neighboring cells.
They are found in plants, particularly in meristems at shoot and root tips.
What are Paneth Cells, and where are they found?
Paneth Cells direct niche geometry and influence asymmetric division to drive differentiation away from the niche.
They are found in the small intestine.
What are the different zones of the Stem Cell Niche?
- SCN (Stem Cell Niche) – Where stem cells reside.
- PZ (Proliferation Zone) – Where progenitor cells actively divide.
- DZ (Differentiation Zone) – Where progenitor cells fully differentiate.
What are the key phases of the hair growth cycle?
- Growth phase (2-5 years, ~0.3 mm/day)
- Inactive phase (same duration as growth phase)
- New cycle begins: new follicle forms, pushing old hair to the surface.
What determines hair color?
Hair color is determined by the type and amount of melanin produced by melanocytes.
It is a polygenic trait influenced by multiple genes, hormones, and environmental factors.
Why does hair turn gray with age?
Pigment production declines with age, leading to reduced melanin and gray or white hair.
What stem cells are found in the hair follicle bulge?
- Follicle stem cells – Contribute to hair regeneration.
- Melanocyte stem cells – Produce pigment for hair color.
What condition is associated with metabolic/endocrine diseases, stress, or drug reactions?
Alopecia Areata – A condition causing hair loss due to autoimmune reactions.
Where are adult neural stem cells found?
Adult neural stem cells are present in specific regions of the brain, where they support neurogenesis and repair.
How does the bone marrow support multiple levels of stem cell behavior?
Bone marrow contains multiple sub-niches, each supporting different types of stem cells and progenitors with distinct roles.
What factors influence stem cell regulation and maintenance?
- Cells within the niche
- Growth factors
- Extracellular matrix (ECM)
- Small molecules
How does the stem cell niche influence self-renewal and differentiation?
The niche provides signals that regulate whether a stem cell undergoes symmetric division, asymmetric division, or remains in quiescence.
