CELL TURNOVER Flashcards
GROWTH
Growth is the process of increase in size resulting from the synthesis
of specific tissue components.
TYPES OF GROWTH
• Multiplicative: Increase in the number of cells by mitosis. Present in all tissues
during embryogenesis
• Auxetic: Increase size of individual cells (eg. Skeletal muscle)
• Accretionary: An increase in intercellular tissue components (eg. Bone and
cartilage)
• Combined
DIFFERENTIATION
Differentiation is the process whereby a cell develops an overt
specialized function or morphology that distinguished it from its parent
cell.
• In this process, genes are expressed selectively, and gene products
act to produce a cell with a specialized function.
MORPHOGENISIS
Morphogenesis is the highly complex process of development of
structural shape and form of organs, limbs, facial features etc. from
primitive cells masses during embryogenesis.
• This involves growth and differentiation with movement of cell groups
relative to others, and focal apoptosis to remove unwanted features
Cell proliferation is fundamental to?
- Development
- Maintenance of steady-state tissue homeostasis
- Replacement of dead or damaged cells
SIZE OF CELL POPULATION
• The size of a cell population depends on the rate of cell proliferation
and death by apoptosis:
• Cell proliferation can be stimulated by pathological or physiological conditions
PHYSIOLOGICAL AND PATHOLOGICAL MAINTANANCE OF CELL POPULATION
Physiological:
• Endometrial tissue during the menstrual cycle
• Thyroid tissue during pregnancy
- Pathological:
- After cell death or tissue injury
CELL PROLIFERATION
Cell proliferation is controlled by signals from the microenvironment
that either inhibit or stimulate cell proliferation.
• Growth can be increased by increasing the rate or shortening the cell
cycle.
The key elements of cellular proliferation are:
• Accurate DNA replication
• Coordinated synthesis of all other cellular constituents
• Equal apportionment of DNA and cellular constituents to daughter cells through
mitosis
CELL CYCLE
The cell cycle is a sequence of events that results in cell division. It
consists of the following phases:
• G1 = Presynthetic growth phase
- Restriction point
- G1/S checkpoint
- S = DNA synthesis
- G2 = Premitotic growth
- G2/M checkpoint
- M = Mitosis
CELL CYCLE CHECKPOINTS
The cell cycle checkpoints ensure that cells with genetic imperfections
do not complete replication.
• The G1/S checkpoint monitors the integrity of DNA before irreversibly
committing cellular resources to DNA replication.
• The G2/M checkpoint ensures accurate genetic replication before the
cell divides. If DNA damage is beyond repair, the cell will either
undergo apoptosis or senescence.
activators and inhibitors of cell cycle
The cell cycle is regulated by activators and inhibitors:
• Cyclins
• Cyclin-dependent kinases (CDKs)
• Cyclin-dependent kinase inhibitors (CDKIs)
• CDKs acquire the ability to phosphorylate protein substrates by
forming complexes with the relevant cyclins.
Increased synthesis of a particular cyclin leads to increased kinase
activity of the appropriate CDK binding partner.
• As the cyclin completes its round of phosphorylation, the associated
cyclin is degraded and the CDK activity abates.
• Therefore, CDK levels wax and wane with corresponding cyclin levels.
CYCLIN-DEPENDENT KINASE INHIBTIORS
- p21 (CDKN1A)
- p27 (CDKN1B)
- p57 (CDKN1C)
- Broadly inhibit CDKs
CYCLIN-DEPENDENT KINASE INHIBTIORS
• Selective effects on CDK4 and CDK6
- p15 (CDKN2B)
- p16 (CDKN2A) • p18 (CDKN2C)
- p19 (CDKN2D)
STEM CELL
• Stem cells are undifferentiated cells that can differentiate into multiple
types of other cells.
• Stem cells are characterized by two important properties:
• Self-renewal: allows maintenance of stem cell pool
• Asymmetric division: one daughter cell enters the differentiation pathway and
gives rise to mature cells, whilst the other cell remains undifferentiated and
retains its self-renewal capacity.