Cell Cycle, Growth, Death and Differentiation

Cell Cycle and Growth

Cell replication

• Organisms need to produce new cells to develop, grow and repair themselves, therefore they divide

• Cells can divide exponentially where the number of cells doubles with each replication (2ⁿ)

The Eukaryotic cell cycle - Interphase and M phase (mitosis + cytokinesis)

• Interphase: the cell duplicates all its components.

  • Gap 1 (G1): the volume of cytosol increases, proteins are synthesised for DNA replication and organelles are replicated.

  • Gap 0 (G0): a temporary phase of no growth or change

  • S: chromosomes are replicated

  • Gap 2 (G2): the volume of cytosol increases, proteins needed for mitosis are synthesised

• Mitosis: the nucleus divides. A parent cell divides into two identical daughter cells. New somatic (body) cells are produced by mitosis, genetic material is also replicated with each daughter cell having a copy.

  •  Prophase: the chromosomes condense, the nuclear membrane breaks down and centrioles begin to make the mitotic spindle.

  • Metaphase: the mitotic spindle fibres attach to centromeres and the chromosomes line up along the middle of the cell on the mitotic spindle

  • Anaphase: The spindle fibres contract, separating the sister chromatids and drawing them towards the poles

  • Telophase: nuclear envelopes appear around each set of chromosomes, the mitotic spindle is dismantled and the cleavage furrow begins.

• Cytokinesis: the cytoplasm divides.

  • In animals a cleavage furrow forms and the  plasma membrane pinches inwards around the daughter cells which then separate

  • In plants and fungi a cell plate forms and new cell membranes and walls are made between the daughter cells.

DNA synthesis

• During the S-phase in Interphase, double stranded DNA is duplicated.

• Each strand of DNA is used as a template to make a new complementary strand, and the result is two identical double-stranded DNA molecules each made up of a new and old strand.

Binary Fission:

• Prokaryotes are single-celled so their cell division results in a new organism, this is binary fission

• Binary Fission: occurs more quickly than mitosis because prokaryotes have less DNA than eukaryotes and are less complex. The DNA is duplicated, the cell then elongates to almost twice its original size, a new cell membrane and wall (cross wall) form between the DNA molecules, dividing the cell. This forms two identical daughter cells.

Regulating the cell cycle 

• Cell division is a carefully regulated process as if cells divide too much or too little, the organism can be negatively affected so if a genetic mutation occurs during the cell cycle, it needs to be repaired or the whole cycle needs to stop.

• Internal checkpoints:

  • G1 checkpoint: ensures the cell is the appropriate size, has enough nutrients

  • G2 checkpoint: ensures the cell is the appropriate size, has duplicated chromosomes correctly

  • M (metaphase) checkpoint: the mitotic spindle is checked to ensure sister chromatids are attached correctly and anaphase will not commence unless they are attached and aligned correctly

• External control of the cell cycle

  • Contact inhibition: If cells encounter too many other surrounding cells, their cell cycle is slowed or halted

  • Mitogens: if neighbouring cells ‘notice’ cells dying, chemicals such as growth factors that stimulate cell division are released

  • Environmental conditions: temperature, pH, and nutrient availability must be correct for cells to begin division

Apoptosis

• Cells need to die for many reasons such as Immune responses, Menstruation, Embryonic development and Brain development.

• Apoptosis: programmed cell death. The cell is methodically broken down by caspases (enzymes) which cleave specific proteins

  • Early apoptotic cells begin to shrink and chromatin is irreversibly condensed. Blebs are formed as the cytoskeleton dismantles, producing projections in the plasma membrane and cells become fragmented and release signals to attract macrophages. Cell fragments are separated into apoptotic bodies consisting of cytoplasm and tightly packed organelles. Macrophages then engulf the apoptotic cell fragments.

• Extrinsic pathway (death receptor/outside of cell): death receptor proteins on the surface of the cell receive signals, usually released by immune cells, from the external environment that the cell needs to die. Once the death receptors have been bound to (signalled), caspase enzymes are activated.

• Intrinsic pathway (mitochondrial/inside of cell): Mitochondria can detect when internal components of the cell are damaged. They release a chemical called cytochrome c, which activates caspase enzymes.

Necrosis

• Necrosis: uncontrolled cell death (i.e. due to injury)

• The cell swells then bursts, causing an inflammatory response (osmotic pressure causes swelling then the cell lysis). The cause of necrosis may be spread to nearby cells, causing them to undergo necrosis as well

Inhibited Apoptosis and Cancer

• Cancer cells: appear amorphous and bloated, often do not perform their required function, can divide indefinitely, carry harmful genetic mutations, and often lose attachment to surrounding cells and undergo metastasis to spread throughout the body. Cancer can be caused by genetic mutations. 

• Tumour suppressor genes (e.g. p53) induce apoptosis if DNA is irreparably damaged. However, if the genes are under-expressed, the cell will continue through the cell cycle and then potentially produce cancerous cells

• Proto-oncogenes promote growth, and if these genes are overexpressed, cell growth will be uncontrolled

• Benign tumour (not cancerous): slow growing, enclosed within a capsule, prevents the abnormal cells from spreading to other parts of the body.

• Malignant tumour (cancerous): arise from benign tumours, have the ability to invade nearby tissues or enter either blood or lymphatic vessels. From here, they can travel all over the body and continue to grow (metastasising)

Stem Cells

• Stem cells: are relatively undifferentiated, can replicate themselves, and become specialised cells

• Embryonic stem cells: are present during early stages of human development

  • Totipotent Stem cells: found in the zygote and can become any type of cell in the body or placental cells (Placental cells are special cells that form the placenta, which is like a temporary organ that grows inside the uterus during pregnancy.)

  • Pluripotent Stem cells: found in the inner cell mass of blastocyst and can become any type of cell in the body

• Adult stem cells: found in small amounts in adult tissues

  • Multipotent stem cells: can become a certain subset of different cells. E.g. haematopoietic stem cells in the bone marrow can become red blood cells, platelets, or white blood cells (split into ectoderm, mesoderm, endoderm)

  • Unipotent stem cells: can become only one type of cell but can divide repeatedly

• Stem cells produced in the lab:

  • Induced pluripotent stem cells: adult cells that have been artificially stimulated to regress back to a pluripotent state

• Stem cells have the organism's entire genome, this means they have the potential to differentiate into specialised cells. The altered expression of specific genes changes the cell's number and type of organelles, shape, size, and progression through the cell cycle. Once specialised, cells cannot naturally regress.