Lecture 6 - Tissue/adult stem cells

Question 1

What are adult stem cells?

Answer 1

undifferentiated cells that are found in various tissues and organs of the body, including bone marrow.

Unipotent and multipotent

Also known as somatic stem cells or tissue-specific stem cells.

Unlike embryonic stem cells, which can differentiate into any cell type in the body, adult stem cells are typically restricted to differentiating into the cell types of the tissue or organ in which they are found.

Question 2

What does development and tissue formation do ?

Answer 2

It results in the loss of pluripotency, as differentiation increases pluripotency decreases.
The acquisition of specialized function results from the expression of a subset of genes.
Fully differentiated cells do not divide (or less frequently).
Limited reversibility and plasticity
A differentiated tissue has a restricted capacity to cope with minor insults, injuries, or normal wear and tear because cells exit cell cycle and cannot divide

Question 3

Which organs in the human body have regenerative capacity?

Answer 3

Liver, skin, bone, heart, brain, skeletal muscle, epithelial cells and neurones.

Question 4

Define adult stem cell

Answer 4

A stem cell present in adult tissues/organs that retain the characteristics of stem
cells – i.e. self-renewal and potency, except that adult stem cells, are usually unipotent or
multipotent.

Question 5

Define self-renewal

Answer 5

The ability of a cell to produce a replica of itself (to divide to maintain stem cells)

Question 6

Define uni/ multipotency

Answer 6

Unlike embryonic stem cells, which are pluripotent, adult stem cells have
limited cell fate decision and usually differentiate into one or several cell types that compose
the organ. (ex: HSC can give rise to lymphocytes, macrophages, red blood cells)

Question 7

Define cellular homeostasis

Answer 7

Constant or periodic generation of new cells to replace old, damaged, and dying cells, or the addition of new cells as needed. Adult stem cells fulfil this role through the process of regeneration/replacement.

Question 8

What does the model of adult stem cell division ensure?

Answer 8

Ensures that cellular homeostasis is maintained. Maintaining a balance between self-renewal and differentiation is critical to cellular homeostasis.
1. Classical stem cell division - self-renewal or transit-amplifying cella (progenitors)
2. Stem cell asymmetry
3. Population asymmetry - dif lvls

Question 9

What is a stem cell niche?

Answer 9

Specialised, tissue-specific microenvironment regulating adult stem cells.

It contains ECM and other cell types that control the activity of stem cells. Adult stem cells are controlled by extracellular and intracellular mechanisms.

Question 10

What is classical stem cell division ?

Answer 10

Classical stem cell division refers to the process by which a stem cell divides into two daughter cells, one of which remains a stem cell, while the other differentiates into a more specialized cell type. This type of cell division is also referred to as “asymmetric division” or “asymmetric cell division,” as it results in the production of two daughter cells with different fates.

Question 11

What is stem cell asymmetry ?

Answer 11

Stem cell asymmetry refers to the process by which a stem cell divides into two daughter cells with different fates.

Question 12

What is population symmetry ?

Answer 12

Population symmetry refers to the property of a population of cells, tissues, or organisms in which the individual members are relatively homogeneous.

Refers to the property of a population of stem cells that are functionally equivalent or interchangeable.

Question 13

How are the components of the stem cell niche divided?

Answer 13

Physical: cell adhesion and ECM

Chemical:
- secreted proteins (paracrine, juxtacrine, endocrine signalling, neurotransmitters) - these cells surround the stem cells and secrete these
- metabolic (Ca2+, ROS (reactive oxidative species), …)

These things sit outside the stem cell and control stem cell activity

Question 14

What is Epigenetic regulation ?

Answer 14

histone modifications and methylation influence the expression of stem cell genes. These are mechanisms to mark a genome for global changes in the way cells are generated

Question 15

What is Transcriptional Regulation?

Answer 15

networks of transcription factors regulate stem cell quiescence, proliferation, differentiation and self-renewal.

Question 16

What is Cytoplasmic determinants?

Answer 16

The asymmetric distribution of proteins governs the mode of cell division.

Question 17

How does BMP signalling control germline stem cell differentiation?

Answer 17

BMP (bone morphogenetic protein) signaling plays a crucial role in the regulation of germline stem cell (GSC) differentiation in the Drosophila ovary.

Cap cells produce TGF𝛽 ligands, which activate BMP signalling. BMP signalling represses bam,
which is required for differentiation.

ECM molecules restrict TGF𝛽 ligand diffusion.

Bam is a master regulator of GSC differentiation.

Overexpression of dpp (or loss of bam) causes
germline tumours.

Question 18

What are the advantages of adult stem cells?

Answer 18

Already ‘specialised’ - induction of differentiation into specific cell types will be easier.
Plasticity - Recent evidences suggest wider than previously thought ranges of tissue types can be derived.
No Immune-rejection - if used in autologous transplantations.
No Teratomas - unlike ES cells.
No Ethical Controversy - sourced from adult tissues.

Question 19

What are the disadvantages of adult stem cells?

Answer 19

Minimal quantity - the number of isolatable cells may be small.
Finite life-span - may have limited lifespan in culture.
Ageing - stem cells from aged individuals may have a higher chance of genetic damage due to ageing.
Immunogenic - potential immune rejection if donor cells are derived from another individual.

Question 20

What are skeletal muscle stem cells and where are they located?

Answer 20

The skeletal muscle stem cell, also known as the satellite cell, is a type of adult stem cell that is responsible for the regeneration and repair of skeletal muscle tissue. These cells are located on the surface of mature muscle fibres, just beneath the basal lamina.

Question 21

What do skeletal muscle SC do during muscle injury or damage ?

Answer 21

The satellite cells become activated and undergo proliferation and differentiation to generate new muscle fibres and repair the damaged tissue. The activation of satellite cells is triggered by various signals, including growth factors, cytokines, and mechanical stress.

Question 22

What is asymmetric cell division ?

Answer 22

Asymmetric cell division is a mechanism by which stem cells can self-renew while simultaneously generating differentiated daughter cells. In the context of skeletal muscle stem cells, or satellite cells, asymmetric cell division plays a critical role in the maintenance of the stem cell pool and the regeneration of muscle tissue.

Question 23

What happens to cells during asymmetric cell division ?

Answer 23

During asymmetric cell division, a stem cell divides into two daughter cells with distinct fates: one daughter cell remains a stem cell, while the other differentiates into a specialized cell type. This process allows for the continual production of new stem cells while also generating a pool of differentiated cells that can contribute to tissue regeneration.

Question 24

How is the basal lamina a component of the niche ?

Answer 24

The basal lamina is a Laminin-containing supramolecular structure that anchors to the cell surface via the Laminin receptors.

Laminin, a major component of the basal lamina, can activate the integrin signaling pathway in satellite cells, promoting their attachment and proliferation.

Question 25

What is the basal lamina and what does it contain ?

Answer 25

The basal lamina is a thin layer of extracellular matrix that surrounds each muscle fiber and separates it from the surrounding connective tissue. It is composed of various proteins, including laminin, collagen, and proteoglycans, and provides structural support and mechanical stability to the muscle fibers.

Question 26

How is the basal lamina invovled in asymmetric division in terms of mitotic spindle ?

Answer 26

The basal lamina also plays a role in regulating the asymmetric division of satellite cells. During division, the orientation of the mitotic spindle is controlled by interactions between the satellite cell and the basal lamina. Changes in the composition or organization of the basal lamina can alter the orientation of the mitotic spindle, leading to changes in satellite cell fate.

Bar1 can block par3

Question 27

How does the remodelling of the basal lamina support asymmetric cell division?

Answer 27

During asymmetric cell division, the basal lamina undergoes a remodeling process that is necessary for the proper orientation and outcome of the division. The remodeling of the basal lamina involves changes in its composition and structure, including the deposition and removal of various matrix molecules, such as laminins and type IV collagens, and the activation of matrix metalloproteinases (MMPs).

Question 28

How do satellite cells control asymmetric cell division ?

Answer 28

In the mammalian skeletal muscles, satellite cells control their asymmetric cell division by remodelling their ECM and driving the asymmetric distribution of Par proteins.

Question 29

WHt happens in invertebrae

Answer 29

Ovaries -> ovalues -> germarium -> 2 germloine SCs thaht are tightlty associated with CAP cell

Forms one germ line stem cell and one cytoblast
Cytoblast - undergoes 4 rounds of cell division tio ake 16 cellls. ONLTY one cell becomres an occyt

Question 30

nltHow do satellite cells control asymmetric cell division ?

Answer 30

In the mammalian skeletal muscles, satellite cells control their asymmetric cell division by remodelling their ECM and driving the asymmetric distribution of Par proteins.

Question 31

What does loss of Dpp Overexpression of bam cause?

Answer 31

Loss of dpp (or overexpression of bam) causes GSC differentiation. The upregulation of bam expression in GSCs promotes their differentiation into cystoblasts, which subsequently divide to produce differentiated germ cells.

Overexpression of dpp (LOSS OF BAM) CAUSES gerline tumours

Question 32

Where are Par proteins prominent in>
?

Answer 32

Par1 abundant ion apical side
Par31 abundant on bssal side
Par3 -