ANHB3323 (18) - stem cells

Embryonic stem cell

All multicellular organisms arise from one cell

most commonly from inner cell mass of blastocyst

Types:

• Pluripotent (inner cell mass)

  • differentiate ONLY into embryonic cells

• Totipotent (blastomere)

  • can differentiate into placental and embryonic cells

Adult stem cell

replace damaged or dead cells

Types:

• Multipotent

• Oligopotent

• Unipotent

[limited differentiation potential)

Types of self renewal (stem cells)

1. symmetric self-renewal = creates cells that are the same as original

2. asymmetric self-renewal = creates original cell + another cell that is slightly more restricted

3. symmetric differentiation = creates 2 cells that are more restricted

Extraction of embryonic stem cells

from inner cell mass of blastocyst = kills embryo (controversial)

Induced pluripotent stem cells

reprogramming fully differentiated adult cells

= embryonic stem cell like properties

Timeline of stem cell discovery

1. 1962 = frog cloned

2. 1983 = produced multinucleate cells

3. 1987 = trancription factors + mammalian cell cloning

4. 1996 = mammal cloned

5. 1998 = mice cloned

6. 2001 = human embryo cloned

7. 2006 = induced pluripotent stem cells generated

8. 2010 = AID pluripotentcy regulator

Enbryonic stem cell uses (5)

1. study in tissue cultures = to understand factors controlling cell differentiation

2. source of human cells for transplantation = tissue engineering

3. cloning

4. somatic cell nuclear transfer

5. induced pluripotent stem cells (IPSCs)

Somatic Cell nuclear transfer (5 general steps)

1. Egg + somatic cell

2. Egg anucleated

3. Somatic cell nucleus isolated

4. Egg + somatic cell combined

5. Gives rise to totipotent cell

Generates autologous cells (patient’s own cells) which can avoid the immune rejection problem

Why is cloning in humans unacceptable? (4 reasons)

1. ethics

2. Genes vs environment

3. status/quality of DNA ('aged')

4. role of maternal cytoplasmic factors and mtDNA

Bivalent Domains

chromatin regions that contain both activating and repressive marks

= maintains embryonic stem cells in 'poised' state

Adult stem cell uses (3)

1. tissue engineering ex vivo (spare parts)

2. Tissue repair by cell therapy

3. Genetically correct autologous cells = treat disease

Examples of tissue repair by adult stem cell therapy (4)

1. Haematopoetic cells = leukaemia

2. Islet cells = diabetes

3. Heart = after heart attack

4. Neurodegenerative disorders = parkinsons etc.

stem cell niche

environment in which they reside

= dominant part in regulating stem cell activity and behaviour

(adult stem cells are all in a niche)

Satellite cells (location and function)

next to plasma membrane under basal lamina (in skeletal muscle)

• activated by external stimuli = differentiate together + upregulation of MyoD

• upregulation of MyoD = differentiates myoblast → myotube

Haematopoietic stem cells

give rise to many blood cells

(found in bone marrow)

2 regions of the body that undergo Neurogenesis

1. Olfactory Bulb (smell)

• in Subventricular zone (SVZ) of lateral ventrical

2. Hippocampus (learning/memory)

• in Subgranular zone (SGZ) of dentate gyrus, in hippocampus

Induced pluripotent stem cell usecase

Direct reprogramming in vivo via viruses/other molecules

Uses:

• disease modelling

• pharmacological screening + toxicity testing (drug development)

• transplanting cells back into patient

Benefits of iPSCs

1. reduced ethical concenrns

2. disease understanding/treatment

3. patient specificity