The Cell - Differentiation and Specialisation

Question 1

Cellular Differentiation

Answer 1

Cellular differentiation is the process by which a less specialised cell becomes a more specialised cell type.
During cell differentiation cells change size, shape, metabolic activity and responsiveness to signals
Leads to functional specialisation
Differentiation occurs during embryonic development - generating a multicellular organism with specialised tissue and organs.
Differentiation occurs in adult life - haematopoiesis (blood cell lineages), wound healing, immune responses, oogenesis and hair growth.

Question 2

Functional Importance of Cell Differentiation

Answer 2

Functional importance of cellular differentiation results in specialisation and organisation into tissues (e.g. cardiac muscles), organs (e.g. heart) and systems (e.g. circulatory system).

Question 3

Why does cell differentiation occur?

Answer 3

1. Change in the gene expression pattern - transcription regulators can act different at different stages in different combinations through the path of cell development and differentiation
   
   2. Changes in cellular environment - responses to cell signalling
   3. Time - Developmental temporal cues
      Stem cell division - stem cell potential may be regained or lost during asymmetric cell division (ACD) or symmetric cell division (SCD)

Question 4

Types of Cell Division

Answer 4

Asymmetric Cell Division (ACD) or Symmetric Cell Division (SCD)

Question 5

Asymmetric Cell Division and Symmetric Cell Division

Answer 5

ACD balances proliferation and self-renewal with cell-cycle exit and differentiation (homeostasis)
Inappropriate asymmetric division can disrupt organ morphogenesis.
Uncontrolled symmetric division can induce tumorigenesis and tissue degeneration.

Question 6

Stem Cell

Answer 6

Stem cell is an undifferentiated cell that is capable of giving rise to indefinite number of cells of the same type that can give rise to other types of cells through the process of differentiation.

Question 7

Types of stem cells

Answer 7

Totipotent
Pluripotent
Multipotent

Question 8

Totipotent

Answer 8

Totipotent cells can differentiate into any cell type (zygote and blastomeres)

Question 9

Pluripotent

Answer 9

Pluripotent can develop into cells of any of the three germ layers (inner cell mass of the blastocyst that give rise to the embryonic stem cells ESCs)

Question 10

Multipotent

Answer 10

Multipotent can develop into several different cell types (haematopoietic and epithelial stem cells).

Question 11

The Cell Cycle

Answer 11

The cell cycle is a complex sequence of events by which cells grow and divide
In eukaryotic cells there are 4 phases of cell cycle: G1, S, G2 and M phase
Some cells cycle continuously (e.g. squamous cells of the epithelium cell of the gastrointestinal tract)
Some cells exit the cell cycle and enter a non-dividing phase G0, from which they can re-enter the cell cycle (hepatocytes).
Some cells permanently remain in G0 (e.g. neurons)
A cell specialises whilst in G0.

Question 12

Cell Lineage

Answer 12

Cell lineage refers to the developmental history of tissue or an organ from the fertilised oocyte (zygote)

Question 13

Mesenchymal Stem Cells

Answer 13

Mesenchymal stem cells give rise to chondrocytes and osteoblasts

Question 14

Ectoderm

Answer 14

Ectoderm cells give rise to neuronal stem cells or epidermal stem cells

Question 15

Haematopoiesis

Answer 15

Haematopoiesis is the differentiation process that leads to the formation of all blood cells from haematopoietic stem cells (HSCs)

Question 16

Cancer

Answer 16

Failure to maintain homeostasis leading to an increase in stem cells e.g. epithelial cancers, leukaemia
Failure during development e.g. Wilm’s tumour
Aberrant differentiation e.g. teratoma

Question 17

Developmental abnormalities

Answer 17

e.g. limb malformation, organ defects

Question 18

Adult diseases

Answer 18

Duchene muscular dystrophy (ROS stress & necrosis of muscle cells).

Question 19

What happens if cellular differentiation/cell cycle goes wrong?

Answer 19

Cancer
Developmental Abnormalities
Adult Diseases

Question 20

Colon

Answer 20

Epithelial layer of human colon consists of single sheet of columanr epithelial cells which form crypts and villi (million of crypts and villi within the colon).
Stem cells are located at the bottom of the crypt.
There are 4 terminally differentiated cell types from a single multipotent stem cells through a number of committed progenitors
1. The colonocytes or absorptive epithelial cells
2. The mucus-secreting goblet cells
3. Peptide hormone-secreting entero-endocrine cells
4. Paneth cells

Proliferation is regulated by Wnt ligand.

Question 21

Crypt Base Columnar Cells (CBCCs)

Answer 21

Crypt base columnar cells (CBCCs) start to differentiate once they are pushed out of the niche at the bottom of the crypt.
The main determinant of CBCCs differentiation is Notch signalling:
Notch on = absorptive fate
Notch off = Secretory fate

Question 22

Skin

Answer 22

Skin has 3 main layers: Epidermis, dermis and hypodermis.
Epidermis is composed of self-regenerating stratified squamous epithelial cells, keratinocytes.
Keratinocytes form the outer protective layer of keratin composed of: Stratum Corneum, Stratum Lucidum, Stratum Granulosum, Stratum Spinosum and Stratum Basale.

Question 23

Epidermis (cell types)

Answer 23

There are three types of differentiated and specialised cells in the epidermis with specific functions:
1. Melanocytes - located in the basal layer (stratum basale), produce and secrete melanin using tyrosinase gene, provide UV protection
2. Langerhans cells - Belong to monocyte lineage, similar to macrophages, involved in immune surveillance
Merkel cells - Belong to epithelial lineage (tactile epithelial cells), function as mechanoreceptors essential for touch sensation.

Question 24

Function of epidermis

Answer 24

1. Protection - Stratum corneum (an anatomical barrier to pathogens), Stratum Spinosum (Immune defence - Langerhans Cells) and Stratum Basale (UV protection - melanocytes)
   
   2. Sensation - Stratum Basale - Merkel cells
   3. Control of evaporation - semi-impermeable barrier to fluid loss
   4. Storage and synthesis - Stratum basale and Stratum Spinosum: Synthesis of vitamin D
      Absorption - Oxygen supply to outermost 0.25 - 0.40 mm of the skin and administration of medicines (ointments, adhesive patch).

Question 25

Types of Cell Death

Answer 25

1. Apoptosis
   
   2. Anoikis
   3. Necrosis
      Autophagy

Question 26

Apoptosis

Answer 26

The death of cells which occurs as a normal and controlled part of growth and development of an organism.
50-70 x 10^6 cells undergo apoptosis in the human adult each day
Cell shrinkage and condensation of chromatin leads to membrane blebbing and organelles disintegrate.

Question 27

Types of apoptotic pathways

Answer 27

Extrinsic Pathway
Intrinsic Pathway

Question 28

Extrinsic Pathway

Answer 28

Extrinsic pathway: Apoptosis is triggered by signals coming from outside of the cell. Two ligands that bind to death receptors are FAS and TRAIL

Question 29

Intrinsic Pathway

Answer 29

Intrinsic pathway: Apoptosis is triggered by stress or damage to the cell.

Question 30

What is Apoptosis used for?

Answer 30

Apoptosis is used for killing cells for:
1. After serving the purpose
2. Self destructive cells (e.g. T cells)
3. Embryogenesis
4. Odd cells
5. Odd cells in highly proliferating organs
Hormonal

Question 31

What can cause apoptosis?

Answer 31

Radiation, anticancer drugs, duct obstruction, heat and mitochondrial permeability can trigger apoptosis

Question 32

Necrosis

Answer 32

Cell death caused by an irreversible injury to cells resulting from exposure to noxious stimuli
Noxious stimuli include infectious agents (bacteria, viruses, fungi, parasites), oxygen deprivation and extreme environmental conditions such as heat and radiation.
During necrosis, in response to injury cells undergo autolysis induced by excessive levels of cytosolic calcium and reactive oxygen species (ROS)
Necrosis in not regulated and is almost always associated with a pathological process.

Question 33

Process of Necrosis

Answer 33

Chromatin clumping
Swollen organelles
Flocculent mitochondria
Cell disintegration and release of intracellular contents

Question 34

Anoikis

Answer 34

A form of programmed cell death that occurs to anchorage-dependent cells when they detach from the ECM
Loss of anoikis can contribute to cancer metastasis.

Question 35

Autophagy

Answer 35

Autophagy is an orderly destruction of damaged organelles, malformed or long-lived, unused proteins as well as intracellular pathogens
Autophagy occurs in response to cellular starvation
Mechanism involves formation of a double membrane vesicle (autophagosome) that encapsulates cytoplasm, malformed proteins, organelles or pathogens and then fuses with lysosome for degradation.

Question 36

What can autophagy provide?

Answer 36

Autophagy provides a source of energy during cell starvation so substrates can be recycled to produce molecules or be used in the TCA cycle.