Lecture 9 - Adult Stem Cells Flashcards

1
Q

What are adult stem cells capable of?

A
  1. Self-renewing
  2. Differentiating into multiple cell types
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2
Q

Adult stem cells are restricted by …

A

Lineage

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3
Q

What happens when haematopoietic stem cells move away from osteoblasts?

A

They undergo specific programmes of differentiation, via a myeloid or lymphoid lineage

  • Osteoblasts line trabecular bone cavities providing support for HSC.
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4
Q

Uses of Adult Mesenchymal stem cells

A
  1. Regenerative medicine
  2. For the study of cellular differentiation
  3. Home to injured tissues where they can differentiate and help repair/regenerate the tissue. Injured tissues are able to secrete both homing signals and differentiation signals.
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5
Q

Two populations of stem cells in the bone marrow

A

Different populations will be recruited to treat different diseases

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6
Q

Division Patterns for tissue homeostasis

A

Most stem cells divide to give rise to Transit Amplifying cell, or a progenitor.

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7
Q

Difference between transit amplifying cell and stem cell

A
  1. TA cells can undergo a limited number of rounds of the division prior to differentiating
  2. Stem cells can undergo unlimited rounds of division.

This protects against the acquisition of mutations within the stem cells.

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8
Q

TA cells in the intestine

A

TA cells undergo 4-6 divisions before moving up the crypt. They undergo a limited number of divisions and differentiate into multiple cell types.

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9
Q

Cancer in the intestine

A
  • Only occur when cells in the intestinal crypt are mutated (stem cells or TA cells)
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10
Q

Familial adenomatous polyposis (FAP)

A
  • An inherited condition in which numerous growths form mainly in the epithelium of the intestine.
  • Caused by mutations in the APC gene on chromosome 5.
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11
Q

The function of the APC gene

A

Responsible for differentiation and outmigration of TA cells from the crypt.

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12
Q

What factors influence the total number of stem cells in an organ and their proliferation rate?

A

Hereditary (Genetic) and environmental conditions
- 30x more risk of FAP colorectal than duodenum (Hereditary factors)
- higher risk of basal cell carcinoma than melanoma (Environmental factors)

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13
Q

Adult stem cell detection methods for mouse (Hair Follicle)

A

Pulse-Chase
1. Label cells with BrdU
2. Dividing cells dilute out label

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14
Q

Why Pulse Chase detection method can be used in adult stem cells?

A

Stem cells in the adult are often slow cycling. They retain the BrdU label.

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15
Q

What is BrdU?

A

Bromodeoxyuridine (BrdU) is a synthetic analog of thymidine.

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16
Q

Adult stem cells detection method in human

A

Clonality
- Stem cells will form clones in vitro.
- They are long living, colony forming units

CFE: Colony forming efficiency

17
Q

Lineage Tracing

A
  • LacZ is induced in bulge cells (Transgenic reporter mouse)
  • Labelled cells are followed during hair growth (anagen)
  • Labelled cells are located in all concentric layers of the hair follicle, sebaceous gland and epidermis
18
Q

Hair follicle bulge cells

A

Multipotent stem cells

19
Q

Stem cell niche

A

The area where stem cells reside
1. Modulate how stem cells behave and participate in tissue regeneration, homeostasis and repair

20
Q

The niche can be cellular or non-cellular

A

In the Drosophila ovary, stem cells reside in a basement membrane where extracellular matrix is the niche

21
Q

Hair follicle stem cell niche

A

Putative niche for the bulge and germ cells is the dermal papilla

Dermal papilla and bulge are derived from cells from different lineages.

22
Q

Bone marrow stem cell niche

A

Osteoblasts are the niche for the hematopoietic stem cells.

The osteoblasts are derived from the mesenchymal stem cells

23
Q

Intestine stem cell niche

A

Paneth cells are the niche for interstitial stem cells

Paneth cells are derived from stem cells, creating their own niche.

Growth of gut organoid from single stem cell

24
Q

Striatum niche

A

In the striatum, two groups as astrocytic stem cells have been identified, and are thought to rely on the blood vessels as a niche.

25
Q

Muscle stem cell niche

A

Muscle stem cells (satellite cells) are located on muscle fibres.

Surrounding extracellular matrix is the muscle stem cell niche

Blood vessels run through the extracellular matrix, and systemic factors can influence the niche

26
Q

Aging of stem cells

A

Apoptosis senescence
Dysfunction in self renewal
Dysfunction in lineage potential

27
Q

Systemic influence on stem cells

A

Alteration of systemic influences can impact the youthfulness of a stem cell and its niche.

The aging of stem cells involves dominant signals from the local and systemic environment