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17 Cards in this Set

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Cell Cycle

G1 - 2n DNA, extremely short, cell groth and some macromolecule synthesis, deletion of damaged DNA.


G1 Checkpoint - DNA damage, environment conditions.


G0 - 2n DNA, cells leave cycle, becomes quiescent, long lasting, can re-enter if signalled e.g. lymphocytes by antigen


S - DNA replication, 4n complement, sister chromatids.


G2 - 4n complement, further growth for mitosis.


G2 Checkpoint - unreplicated or damages DNA, maintain genomic stability.

Mitosis

Prophase - chromosomoes condense


Metaphase - attach to spindle fibres


M checkpoint - ensures correct allignment


Anaphase - sistser chromatids pulled to poles by spindle fibres.


Telophase - membrane reforms, cyctokinesis, ises a cell plate along equatorial plane.

Mitogens

Mitogens - Stimulate cell division and entry into the cycle e.g. PDGF (widespread effect ie. wound healing), FGF (pleiotropic effects), TGF-B (stimulate proliferation) & Erthropoietin (induced BFU-E and CFU-E proliferation.

Cell Cycle Control

Regulated by cyclins and cdks - cyclins associate with different cdks in each phase, fluctuate expression. RB is a tumour supressor, which is dephosphorylated (activated) after mitosis preventing G1-S transition, and then phosphorylates (inactivated) allowing the cycle to proceed.

Apoptosis & Necrosis

Apoptosis - programmed cell death (for development, homeostasis or damaged cells) physiological, controlled. Condensation, fragmentation then phagocytosis.Causes blebbing of bodies.




Necrosis - response to disease, pathological, organs swell, membranes rupture, leakage and inflammation. Can cause lesions and nuclear pores.

Stem Cells: Characteristics

Have ability to self- renew and to differentiate. Divide asymmetrically, one remains a stem cell whilst the other specialises.




Totipotent - can specialise to entrie organism


Pluripotent - can be virtually any cell, cannot form own organism as no placenta for development.

Embryonic Stem Cells: In vitro & Transcriptional Control

Occur in the ovary during embryogenesis. If grown in vitro, ICM is plated and grown in nutrient medium, cells divide and form colonies, then re-plated to creat a pluripotent stem cell pool. Sub-cutaneous injections into immunocompromised mice form teratomas (contain differentiated cell types from all 3 germ layers, shows pluripotency). Express high telomerase levels, to maintain telomere funciton in dividing cells.




Transcriptional Control - all control pluripotency. Oct-4 (a TF expressed at blastocyst stage in inner cell mass), Sox2 (TF, forms complex with Oct-4, activates similar genes) and Nanog (expressed after Oct-4).

Adult Stem Cells

Adult - multipotent, can self renew but limited by reduced telomerase levels. Also differentiate to maintain activity of cells by replacgin those lost by injury or disease. Long lived but slow cycling, have high ABC transporter expression (remove toxins) and aldehyde dehydrogenase (makes acetic acid). They are rare, create a precursor before fully differentiating (progenitor).

Epidermal Stem Cells

EpSC - continually renewed, becomes more differentiated nearer to the surface (become keratinocytes). Basal layer keratinocytes subdivided into epidermal stem cells, transit amplifying cells (undergo some division, terminal differentiation). Psoriasis - caused by uncontrolled proliferation, causes inflammed plaques on skin.

Haematopoietic Stem Cells

HSCs - located in micro-environments in bone marrow, O2 & nutrients allowing for a long lifespan. Also in perpheral blood. One SC in injection can repopulate entire system following lethal irradiation. Could be used for chemotherapy/ Leukaemia treatment instead of transplants.

Haematopoiesis

Stem cells can make many cell types including Erthuocytes, Leukocytes and platelets. Early HSCs are found in aorta-gonadmesonephros (AGM) region, later in bone marrow. May be possible to reverse cycle.




Regulation by interellular signalling with secreted factors modulating proliferation e.g. SCF, EPO, TPO.

Erthrocytes: Pathway & Anaemia

HSC --> common myeloid progenitor --> Burst formingU-E --> colonyforming U-E --> Erthrocyte. Shortage of euthrocytes stimulates the kidney to produce EPO, late is negatively suppressed when levels high enough.




Anaemia - Causes Kidney failiure, decreases erthropoietin levels, only recovered by EPO administration.

Platelet Pathway: Megakaryocytes

Megakaryocytes - rare cells, give rise to platelets, controlled by TPO. Large, indented, a-granule formation, dilated dearcation membrane system and platelet formation. Formed when force of blood rips megakaryocytes off in sinus.




TPO regulation - Initiates Ras- dependent signalling cascade, controlled by TFs.


HSC --> Progenitor Mega. --> Mature Mega. --> proplatelet Mega. --> platelet.




Disorders from abnormal differentiation e.g. Leukaemia, hypersensitive to thrombopoietin, causes spontaneous clotting.

Bone

a

Osteoblasts

a

Bone Remodelling & Development

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FGF: Bone development

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