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Trinity Term 1 > Stem cells > Flashcards

Stem cells Flashcards

1
Q

What is a stem cell?

A
  • cells able to divide to give rise to new cells required to make and maintain the cells, tissues and organs of multicellular organisms.
  • undifferentiated, not engaged in a specific physiological function
  • have “potential”
  • “self-renewal”
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2
Q

Describe “potential”

A
  • aka potency
  • a population of stem cells can be the source of some, many or even all cell types in an organism
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3
Q

Describe “self-renewal”

A

maintained through rounds of cell division

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4
Q

Describe asymmetric cell division

A

gives rise to one “stem cell” and one “committed cell”

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5
Q

Describe symmetric division with asymmetric population behaviour

A

gives rise either to two “stem cells”, OR two “committed cells”

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6
Q

Cells acquire … during development

A

more restricted fates

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7
Q

Describe development from the zygote

A
  • blastula
  • gastrula
  • germ cells (male, female) and derm layers (endo, meso, ecto)
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8
Q

Describe the endoderm

A
  • stomach cells make digestive tube
  • thyroid cells in pharynx
  • alveolar cells in respiratory tubes
  • intestinal epithelium cells
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9
Q

Describe the mesoderm

A
  • dorsal notochord
  • paraxial bone tissue
  • intermediate kidney tubule cells
  • lateral erythrocytes, lymphocytes and monocytes
  • facial muscles in the head
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10
Q

Describe the ectoderm

A
  • epidermal fibroblast on outer surface
  • neurones of CNS
  • melanocytes of neural crest
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11
Q

Describe fate-mapping

A

identifies early cells

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12
Q

Describe totipotency

A
  • makes everything, including extraembryonic tissue (placenta)
  • zygote and morula
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13
Q

Describe pluripotency

A
  • can make all cells in the embryo and adult
  • germ layer specified
  • blastocyst
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14
Q

Describe multipotency

A
  • all cell types of a tissue or organ
  • germ layer specified
  • blastocoel and grastula
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15
Q

Describe oligopotency

A

can make several, related cell types

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16
Q

Describe unipotentcy

A

can make only one cell type

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17
Q

What happens at the grastula boundary?

A
  • differentiation
  • proliferation
  • migration
  • signalling
  • morphogenesis
  • organogenesis
  • growth
  • homeostasis
  • regeneration
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18
Q

Describe the lineage process

A
  • stem cells become progressively more ‘determined’ during development
  • potency deceases as lineage progresses
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19
Q

Describe adult stem cells

A

continue to maintain our tissues and organs in response to ”wear and tear”, ”infection/disease” and
“other environmental factors/toxins”

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20
Q

Describe developmental stem cells

A

maintained as adult stem cells

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21
Q

Which stem cells makes intestinal epithelial cells?

A

intestinal stem cells

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22
Q

Which stem cell makes lymphocytes, monocytes and erythrocytes?

A

haemtopoetic stem cells

23
Q

Which stem cells makes skin fibroblast?

A

epidermal stem cell

24
Q

Describe transit amplifying cells

A
  • derived from stem cells later in development and adult stem cells
  • lineage committed
  • neither differentiated nor “self- renewing”
  • divide several times to expand to a population of cells that eventually differentiates
  • reduces the number of divisions a stem cell makes
25
Q

Describe gene regulation inside stem cells

A
  • TFs
  • epigenetic/chromatin modifications
  • microRNAs
  • external signals can drive differentiation to the required fates
  • for control and manipulation of stem cells
26
Q

Describe TFs in stem cells

A
  • maintain a stable undifferentiated state
  • supress genes that drive differentiation
27
Q

Describe epigenetic/chromatin modification in stem cells

A
  • histone modifications
  • DNA methylation
  • transcriptionally silence regions that would lead to differentiation
  • allow expression of genes for the present state
28
Q

Describe microRNAs in stem cells

A

alternate splicing of transcripts

29
Q

ICM

A

inner cell mass

30
Q

Describe the production of mammalian pluripotent embryonic stem cells

A
  • taken from the ICM of embryos
  • highly defined mix of media and growth/signalling factors
  • maintained in an undifferentiated state
  • different levels of readiness to differentiate
31
Q

Describe the different levels of readiness to differentiate

A

naive > formative > primed

32
Q

Describe mammalian pluripotent ESCs

A
  • pluripotent
  • able to form teratomas
  • distinct gene expression profile, associated with
    animal germlines
33
Q

Describe an embryo

A
  • trophectoderm
  • inner cell mass
  • primitive endoderm
34
Q

Human embryonic stem cells can

A

self-organise and pattern in culture

35
Q

Describe the in vivo evidence of ESC pluripotency

A
  • take blastocyst from mouse with white fur
  • inject ESC from mouse with black fur to create a chimera
  • second generation you can get a mouse with black fur
36
Q

Summarise the in vivo evidence of ESC pluripotency

A

generation of donor genotype in the F2 confirms contribution to the chimeric germline

37
Q

Describe gene targeting for transgenic mice

A

target gene undergoes homologous recombination

38
Q

Describe random integration for transgenic mice

A

integration and insertion within a random gene

39
Q

Describe assaying pluripotency

A
  • in vitro experiments study cell competence and regulation over time
  • in vivo reimplantation of ESCs back into embryos allows observation of their contribution
  • genetic manipulation of cells for transgenic mice
40
Q

Describe iPSCs

A
  • 4 TFs responsible for reprogramming activity
  • form teratomas
  • can contribute to all 3 germ layers, and the germline
41
Q

Describe Gurdon’s expts

A
  • nuclear transfer in frogs
  • prove the genome is not diminished as a method of gene regulation during differentiation
  • challenged prevailing theory that cells fates were stable
  • frog egg cytoplasm could reprogram the transplanted nucleus of a differentiated cell
42
Q

Which are the 4 TFs necessary for reprogramming?

A
  • Oct3/4
  • Sox2
  • Klf4
  • c-Myc
43
Q

c-Myc

A

oncogene

44
Q

Describe transcriptional control in “primed” pluripotent cells

A
  • levels of TFs vary stochastically
  • addition of BMP4 pushes cells with low Oct4 to extraembryonic fates
45
Q

Describe epigenetic/chromatin based regulation of primed human pluripotent stem cells

A
  • genes required for pluripotency are ON
  • genes required for later differentiation are OFF
  • genes that might need to switch on soon are in a BIVALENT state
46
Q

Describe gene bivalence

A

ready to switch on or to be
silenced depending on the initial differentiation decision made

47
Q

Describe haematopoietic stem cells (HSCs)

A
  • relatively rare (40k-200K)
  • produce >200 billion RBCs alone
  • > 2.3 million cells produced per second
  • different progenitors in the lineage with different potencies
48
Q

Where did the stem cell concept arise?

A

study of the bone marrow transplants into irradiated mice

49
Q

How are different HSCs identified

A
  • creating antibodies to distinct combinations of cell surface markers
  • FACS allows them to be isolated from the rest of the population
50
Q

FACS

A

Fluorescence Activated Cells Sorting

51
Q

Which diseases and conditions are treated with HSCs?

A
  • sickle cell anaemia
  • autoimmune diseases
52
Q

Describe adult intestinal stem cells

A
  • Paneth cells at the base of the intestinal crypts
53
Q

What is one underlying cause of ageing?

A

the capacity of stem cells to replicate and maintain tissues is limited

Trinity Term 1 (38 decks)

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