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Biology of stem cells, ageing and cancer > Stem cells > Flashcards

Stem cells Flashcards

1
Q

Progenitors

A

Cells that proliferate for a limited number of cycles before differentiation

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2
Q

Cell lineage

A

developmental history of a differentiated cell as traced back to the cell form which it arises

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3
Q

Blastomere

A

the cell type of the early embryo that is generated by cleavage of the zygote

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4
Q

Blastocyst

A

the spherical embryo at the time of implantation, consisting of the primary tissue types

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5
Q

What are the three primary tissue types?

A

trophectoderm
epiblast
primitive endoderm

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6
Q

Trophectoderm

A

precursor of the placenta

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7
Q

Epiblast

A

the founding tissue of the embryo proper that gives rise to all fetal tissues

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8
Q

Primitive endoderm

A

extraembyronic tissue that initially covers the epiblast surface and later gives rise to the yolk sac tissue

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9
Q

Potency

A

ability of a cell to differentiate into one or more cell types

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10
Q

Totipotency

A

ability of a cell to give rise to a fully functional organism, both embryonic and extraembryonic tissues

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11
Q

Pluripotency

A

ability of a cell to develop into all embryonic but not extraembryonic cell types, including the germ cells

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12
Q

What are the hallmarks of pluripotency?

A

expression of pluripotency TFs
teratocarcinoma formation

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13
Q

Germ layers

A

the first specialised precursors of different embryonic cell types

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14
Q

Ectoderm

A

Surface, neural and neural crest
makes skin, PNS and CNS

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15
Q

Mesoderm

A

axial, paraxial, intermediated and lateral
makes blood, heart, muscle and kidneys

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16
Q

Endoderm

A

gut and internal organs
makes liver, pancreas, intestines

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17
Q

How is cell lineage decided during gastrulation?

A

in a regionalised manner- so the location of a cell predicts its identity in response to distinct signals that activate lineage specific TFs

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18
Q

Epithelium

A

cells that line the surface of a structure, characterised by tight junctions and polarised morphology

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19
Q

Epithelial to mesenchymal transition

A

a process during which cells lose their epithelila characteristics, gain a less regular appearance and become migratory
breakdown of basement membrane and loosening of cell cell contacts

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20
Q

Neuromesodermal progenitors

A

bipotent- paraxial mesoderm
future skeletal muscle, bone, cartilage and vertebrae
OR spinal cord

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21
Q

What do defects in neuromesodermal progenitors lead to?

A

spina bifida
currarino syndrome
sacral agenesis
sponylocostal dysotosis

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22
Q

What do haematopoietic stem cells give rise to?

A

all blood cell types

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23
Q

Aorta-gonad-mesonephros region

A

embryonic tissue originating from the para-aortic sphlanchopleura and consisting of the dorsal aorta and urogenital ridges
involved in generating HSCs prior to onset of haematopoisis in fetal liver

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24
Q

Why are embyros and stem cells difficult to study?

A

they have small cell numbers and have difficulties with in utero development and ethics

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25
How do you capture pluripotent embryonic stem cells?
plate on layer of feeder cells (irradiated stromal cells from later embryos) once they have divided a few times disaggregate and replate
26
What are the critical signals to maintain cells in a self-renewing undifferentiated state?
mice- leukaemia inhibitory factor humans- FGF2 and TGF beta
27
What are the main pluripotency factors expressed by ESCs?
Oct4 Nanog Sox2
28
3D
remove signals that keep cells in an undifferentiated state such as BMP and LIF (mice) and FGF2 (humans) grow in aggregates in the presence or absence of signals
29
Advantages of 3D approach
recapitulates more accurately ambryonic development
30
Disadvantages of 3D approach
difficult to observe or dissect the role of individual signals
31
2D / adherent
plate a defined number of cells on the right substrate or ECM remove signals that keep cells in an undifferentiated state such as BMP/LIF/FGF2 grow in a defined medium with appropriate amounts of signals
32
Advantages of 2D approach
more tractable system for live imaging and is easier to test the role of specific signals
33
Disadvantages of 2D approach
loss of cell interactions that may occur in vivo
34
Microcephaly
neurodevelopmental disorder in which infants are born with an abnormally small brain due to various autosomal recessive mutations causes neurological defects and seizures
35
Capturing cells in vitro
dissociate cells and plate on laminin in the presence of cytokines FGF2 and EGF single cell can generate identical daughter cells and differentiate into glia/neurons after removal of cytokines
36
Differentiated cells characteristics
do not divide or do it less frequently limited reversibility and plasticity restricted capacity to cope with injuries, insults or wear and tear
37
Conrad Waddington's epigenetic landscape
illustrates the progressive nature of differentiation
38
What organs in the body have regenerative capacity?
liver epithelial cells skeletal and cardiac muscle brain blood cells
39
Adult stem cells
stem cells present in adult tissues and organs that retain the characteristics of stem cells such as self renewal and potency but are usually unipotent or multipotent, limited cell fate decision
40
Cellular homeostasis
constant or periodic generation of new cells to replace old damaged or cying cells or the addition of new cells as needed by regeneration/replacement by adult stem cells
41
Classical stem cell division
produces transit amplifying or progenitor cells which then differentiate
42
Stem cell assymetry
one progenitor cell is produced
43
Population asymmetry
entire cell population has some cells that will become progenitor cells and some that remain as stem cells
44
Stem cell niche
specialised specific microenvironment regulating adult stem cells physically and chemically
45
How does the stem niche regulate stem cells?
physical- cell adhesion and ECM chemical- secreted proteins (paracrine, juxtacrine, endocrine, NTs)
46
Epigenetic regulation
histone modifications and methylation influencing the expression of stem cell genes
47
Transcriptional regulation
networks of TFs that regulate stem cell quiescence, proliferation, differentiation and self renewal
48
Cytoplasmic determinants
assymetric distribution of proteins that govern the mode of cell division
49
Drosophila creation of oocyte
ovarian germline stem cells divide to generate one stem cellm and one cytoblast cell these divide into many more before selection of the oocyte
50
How does BMP signalling control germline stem cell differentiation?
cap cells produce TGF beta ligands these activate BMP signalling this represses BAM which is required for differentiation
51
What causes germline tumours?
overexpression of DPP or loss of BAM
52
What causes germline stem cell differentiation?
loss of dpp or overexpression of BAM
53
How do skeletal muscle cells repair muscle tears?
assymetric cell division in stem cell maintainance
54
Basal lamina
part of the stem cell niche, layer of ECM secreted by epithelial cells remodelling of this supports assymetric cell division
55
How are adult stem cells anchored to their niche?
cadhenin mediated physical cell-cell adhesion integrin mediated cell-ECM interactions
56
How do cadhenin mediated cell cell adhesions work?
a-catenin and b-catenin associate with intracellular domain of cadherins help to cluster cadherin molecules and form adherens junctions
57
How do integrin mediated cell-ECM interactions work?
intracellular domains of integrins interact with actin cytoskeleton network through talin proteins to cluster integrin molecules together
58
What other properties do stem cell niches have?
signalling molecules are secreted by the cell in high concs close to the stem cell causing self renewal and regulates proliferation grow cells being used to treat a wound prevention of premature ageing
59
How is asymmetric cell division important for cell polarity?
the cell that is away from the niche will not have any signals anymore so will be on the path of differentiation
60
How does competition play a role in quality control of stem cells?
there is still some cadherin and integrin signalling but if even a little bit of this is lost it will induce differentiatoin
61
Stem cell ageing
old stem cells lose cadherin which means that they are lost from the niche, so are more susceptible to infections, becoming more clonal, and mutations
62
Gut crypt structure
tube of cells with stem cell like cells in a niche at the distal end, and differentiated cells at the proximal end
63
Gut crypt structure
tube of cells with stem cell like cells in a niche at the distal end, and differentiated cells at the proximal end stem cells surrounded by paneth cells and basement membrane
64
Paneth cells
cells surrounding the stem cells at the bottom of the crypt that secrete many different peptides and small molecules that regulate the gut microbiome, and signals to Lgr5
65
Lgr5
Receptor that responds to Wnt signalling
66
How can mini guts be made ?
single stem cell populations can be isolated and amplified, then given growth factors and Lgr5+
67
LGR-EGFP transgenic mice
instead of the crypt looking organised, the adenomas mean that paneth cells and the lgr5 transgene is expressed all the way up the crypt, as they are activated and therefore not in the right place
68
How can pluripotency be used to make organoids?
reprogramming skin fibroblasts or using embryonic stem cells taking stem cells from gut epithelium and sorted using FACs
69
FACS
fluorescent activated cell sorting
70
What is the role of Wnt signalling?
induces local proliferation and EphB expression local cell expansion Eph-Ephrin repulsive force which generates bud formation
71
How is stem cell reprogramming used as an experimental tool?
research for intestinal stem cells, intestinal differentiation and epithelial infections
72
How is stem cell reprogramming used as a diagnostic tool?
for cystic fibrosis, mutational analysis in CRC drug absorption and metabolism
73
How is stem cell reprogramming used as a therapeutic tool?
potential regenerative therapy for microvillus inclusion disease, ulcerative collitis and post-endoscopic mucosal resection

Biology of stem cells, ageing and cancer (5 decks)

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