Stem Cells Flashcards

(32 cards)

1
Q

four pathways for stem cells

A
  1. self renew
  2. die
  3. become senescent
  4. differentiate (mature)
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2
Q

define senescence

A

stem cell can be metabolically active but not replicate

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3
Q

define symmetric and asymmetric cell division for stem cells

A

symmetric: may produce two self-renewing stem cells or two daughter cells that will differentiate

asymmetric: produces one self-renewing cell and one committed to differentiation

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4
Q

what is the importance of cell division symmetry/asymmetry?

A

maintaining cell homeostasis (numbers of overall cells)

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5
Q

name three main types of stem cells

A

Embryonic Stem Cells (ES Cells)
Induced Pluripotent Stem Cells (iPS cells)
Adult / tissue-specific stem cells

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6
Q

define totipotent

A

capable of generating ALL cell types that are necessary for embryonic development: entire embryo AND extra-embryonic tissues

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7
Q

define pluripotent t

A

can produce all cell lineages in entire organism

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8
Q

Are ES and iPS cells totipotent or pluripotent?

A

pluripotent
cannot produce extra-embryonic tissues but capable of producing all cell lines

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9
Q

where do ES cells come from?

A

the pluripotent stem cells of the mammalian INNER CELL MASS (ICM)

from inside the blastocyst

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10
Q

how do blastocysts arise? name the key parts

A

fertilised egg divides multiple times.

ICM surrounded by trophectoderm outer layer
fluid filled cavity

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11
Q

why are ESCs useful for tissue culture?

A

they can be differentiated to almost any cell type with correct differentiation protocol (correct media which signals to stem cells)
they self-renew indefinitely in culture

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12
Q

what are iPS cells

A

ADULT cells
manipulated to take on the properties of ES cells

(avoid ethical implications of ESCs)

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13
Q

what are some ways to check that cells are pluripotent?

A

pluripotent marker genes (extract DNA to find)
multilinear differentiation in vitro
teratoma formation
chimera formation

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14
Q

what is a teratoma?

A

tumour containing cells of all three germ layers, confirming that cells are potent

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15
Q

how is chimera formation done?

A

ES cells can be injected back into a developing blastocyst
they incorporate into the ICM
take part in forming a chimeric animal with a mixture of ordinary and ES-derived cells

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16
Q

Define allogenic

A

cells from a donor that is NOT the patient
can be stored for use in ANY patient
ie. universally usefulde

17
Q

define autologous

A

cells from patient modified and reintroduced
immune system rejection often means this is more viable than allogenic cells

18
Q

how can stem cell renewal be enabled?

A

by blocking all other pathways (die, senesce, differentiate)
by influencing EXTERNAL SIGNALS, TRANSCRIPTION FACTOR network and chromatin state

19
Q

what two umbrella factors influence stem cell regulation?

A

EXTERNAL factors from the stem cell’s microenvironment (stem cell niche)

INTERNAL factors
intrinsic to SC, regulate its response to external cues

20
Q

Explain mechanisms of external factors influencing stem cell regulation

A
  • physical mechanisms (eg. structural / adhesion factors in ECM)
  • biochemical mechanisms (eg. signalling)
21
Q

what are the three mechanisms of internal factors influencing stem cell relegation?

A

cytoplasmic determinants

transcriptional regulation

epigenetic regulation

22
Q

how do cytoplasmic determinants (internal factor) influence stem cell regulation?

A

stem cell division can be asymmetric because a cell fate determinant is localised to one side of the cell –> allocated to one of the daughter cells upon division

23
Q

define transcriptional factors and what their purpose is

A

proteins that REGULATE GENE EXPRESSION by controlling the rate at which DNA is transcribed to RNA

process is crucial for differentiation / response to environmental stimuli

24
Q

how do transcriptional factors affect SC regulation?

A

specific transcription factors in embryonic stem cells maintain pluripotency: “ES-critical genes”

25
name the four key genes that are ES-critical transcription factors (ie. necessary in ES cells and transforming adult cells into iPS cells)
OKSM: Oct4 Klf4 Sox2 Myc NOTE: less that 0.1% of cells that receive OKSM actually become iPSCs!
26
how does the uptake of OKSM change gene control systems and structure?
changes the state of chromatin which packages DNA: Myc-induced cell proliferation --> loosening of chromatin structure --> promotes binding of other three transcription factors (sites more accessible)
27
define epigenetic regulation
the mechanism by which gene expression is altered without changing the underlying DNA sequence
28
key mechanism of epigenetic regulation
DNA methylation - methyl groups added to DNA molecule, affects gene expression without altering DNA sequence can lock gene in "off" position, unable to be transcribed
29
how is DNA methylation (epigenetic regulation) used to regulate SCs?
addition of methyl groups silences gene expression --> turn off pluripotency genes during differentiation
30
how does epigenetic regulation and transcriptional factors interact to regulate SCs?
epigenetic change often occurs first - eg. loosen chromatin to increase accessibility of OKSM once OKSM bound, can then recruit chromatin remodellers -- can sustain / reinforce epigenetic changes --> positive feedback loops
31
advances in iPS technology: different methods of introducing transcriptional factors include
various different viruses direct protein introduction direct RNA introduction reprogramming with small molecules
32
important applications of ES/iPS cells
disease modelling screening / testing for personalised medicine source of cells for therapy that will not be rejected by immune system