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MED310 > Stem Cells > Flashcards

Stem Cells Flashcards

1
Q

Totipotent

A

Can become any cell in body or placenta

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2
Q

Pluripotent

A

Can become any cell in body

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3
Q

Multipotent:

A

Can become any cell within a specific germ layer or cell lineage

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4
Q

Steps of cell fate

A

Fertilised egg > totipotent stem cell > FATE decision

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5
Q

Embryonic stem cells

A
  • Pluripotent
  • From embryonic tissues
  • Not committed to a specific fate
  • Self-renewing
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6
Q

Adult Stem Cells

A
  • Multipotent
  • From adult tissues
  • Limited resource/difficult access
  • Limited renewal
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7
Q

Induced Pluripotent Stem Cells

A
  • Pluripotent
  • From adult peripheral tissue
  • Genetically manipulated e.g fibroblast
  • Self-renewing, but not for indefinite time
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8
Q

Original protocol

A
  • Retroviral transduction
  • Introducing pluripotent TFs
  • Major rearrangement of epigenome
  • Differentiation into cell type
  • Clear fibroblast for hard wired info
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9
Q

What processes are requires for cells do go from fibroblast to neurons and glia ??

A

+ Transcription factors or miRNAs

SDR

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10
Q

What processes are required to go from fibroblast to iPSCS?/

A

Fribroblasts > + transient pluripotency factors expression ( epigenetic actviation)
> unstable intermediates > continued expression of pluripotency factors > iPSCs

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11
Q

Unstable intermediates

A

Unstable intermediates - 2 pathways
PDR> + neuralising condition to a neural progenitor
OR
Continued expression of pluripotency factors > iPSCs

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12
Q

Cheaper and faster alternatives

A

Fibroblast straight to neurons and glia

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13
Q

IPSCs

A

Large quantities

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14
Q

Fibroblast to Neuron

A

one shot

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15
Q

iPSC reprogramming

A

Rejuventation

old and young fibroblasts to iPSCc motor neuron

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16
Q

Direct Reprogramming

A

Ageing maintenance

YOung and old fibroblast&raquo_space; young Fib-iMN and Old Fib -iMN

17
Q

IPSC-

A

wiped out epigenome
Mimic embryonic stage > result sc are embryonic like
Issue when studying neurodegeneration> often in older population

18
Q

What is the key difference between direct and iPSPC reprogramming ?

A

Direct allows preservation of some of the ageing features

19
Q

Potential for Stem cells

A

• Exploring disease mechanisms
– Study how basic cellular mechanisms are disrupted in disease
• Drug discovery
– High-throughput assays will identify targets. For example, using hSC cell-derived neural cells for an assay to screen drugs for Alzheimer’s disease
• Toxicology testing
- Identify environmental toxins

20
Q

ALS

A

ALS is one of the most common adult onset motor disorders, characterised by progressive degeneration of upper and lower MNs

21
Q

ALS mutations response for 60%of familial cases

A

SOD1, TARDBP, FUS and C9ORF72

22
Q

Difference between clinical ALS and Familial ?

A

clinically undistinguishable

- no in vitro model only a cellular model

23
Q

Astrocytes

A

Astrocytes- support MN metabolic processes and GFs

- neural support cell

24
Q

Drug discovery protocol in ALS patients -

A
  1. skin biopsy of ALs patient
    2 - Donor fibroblast culture
  2. iNPCs - cellular programming with reprogramming genes
  3. Neural cell aggregates
  4. MN and astrocytes in culture
  5. Robotic drug screening - test one chemical compound per well ** identify therapeutic compounds and disease mechanisms**
25
Q

MS Demyelinating disorder - Drug discovery

A

Oligodendrocyte precursor cells in a well with test compunds
- pre myelinatiing oligodendrocyte
- fix and anti MBP immunostain
- automated image acquisition and quantification
***
- treated with 727 drugs
stained for myelin
looked for compounds promoting myelin - 34

26
Q

Drug screening in AD

A
  • made patient cortical Neurons
  • ipsc - based trial for mutiple individuals
    1. iPscs
      1. patient cortical neurons
      2. pharmaceutical compound library
      3. chemical structure- based clustering and combination analysis
      4. Anti-ab cocktail
27
Q

Stem cell transplants in AD patients

A
  • Provide injured area with trophic factors
  • Induce activation and proliferation of endogenous neural stem cells
  • Partial cell replacement

MED310 (18 decks)

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