The Cell - Differentiation and Specialisation Flashcards
Cellular Differentiation
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.
Functional Importance of Cell Differentiation
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).
Why does cell differentiation occur?
- 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
- Changes in cellular environment - responses to cell signalling
- 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)
Types of Cell Division
Asymmetric Cell Division (ACD) or Symmetric Cell Division (SCD)
Asymmetric Cell Division and Symmetric Cell Division
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.
Stem Cell
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.
Types of stem cells
Totipotent
Pluripotent
Multipotent
Totipotent
Totipotent cells can differentiate into any cell type (zygote and blastomeres)
Pluripotent
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)
Multipotent
Multipotent can develop into several different cell types (haematopoietic and epithelial stem cells).
The Cell Cycle
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.
Cell Lineage
Cell lineage refers to the developmental history of tissue or an organ from the fertilised oocyte (zygote)
Mesenchymal Stem Cells
Mesenchymal stem cells give rise to chondrocytes and osteoblasts
Ectoderm
Ectoderm cells give rise to neuronal stem cells or epidermal stem cells
Haematopoiesis
Haematopoiesis is the differentiation process that leads to the formation of all blood cells from haematopoietic stem cells (HSCs)
Cancer
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
Developmental abnormalities
e.g. limb malformation, organ defects
Adult diseases
Duchene muscular dystrophy (ROS stress & necrosis of muscle cells).
What happens if cellular differentiation/cell cycle goes wrong?
Cancer
Developmental Abnormalities
Adult Diseases
Colon
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.
Crypt Base Columnar Cells (CBCCs)
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
Skin
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.
Epidermis (cell types)
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.
Function of epidermis
- Protection - Stratum corneum (an anatomical barrier to pathogens), Stratum Spinosum (Immune defence - Langerhans Cells) and Stratum Basale (UV protection - melanocytes)
- Sensation - Stratum Basale - Merkel cells
- Control of evaporation - semi-impermeable barrier to fluid loss
- 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).
Types of Cell Death
- Apoptosis
- Anoikis
- Necrosis
Autophagy
Apoptosis
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.
Types of apoptotic pathways
Extrinsic Pathway
Intrinsic Pathway
Extrinsic Pathway
Extrinsic pathway: Apoptosis is triggered by signals coming from outside of the cell. Two ligands that bind to death receptors are FAS and TRAIL
Intrinsic Pathway
Intrinsic pathway: Apoptosis is triggered by stress or damage to the cell.
What is Apoptosis used for?
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
What can cause apoptosis?
Radiation, anticancer drugs, duct obstruction, heat and mitochondrial permeability can trigger apoptosis
Necrosis
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.
Process of Necrosis
Chromatin clumping
Swollen organelles
Flocculent mitochondria
Cell disintegration and release of intracellular contents
Anoikis
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.
Autophagy
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.
What can autophagy provide?
Autophagy provides a source of energy during cell starvation so substrates can be recycled to produce molecules or be used in the TCA cycle.
