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A cell that has the capabilities for unlimited self-renewal Usually slow cycling

Stem Cell. A cell that has the capabilities for unlimited self-renewal Usually slow cycling Able to give rise to at least one differentiated, somatic, cell type. Somatic Cell. Terminally differentiated cells Some limited proliferative capability- e.g. Transit amplifying cell.

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A cell that has the capabilities for unlimited self-renewal Usually slow cycling

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  1. Stem Cell A cell that has the capabilities for unlimited self-renewal Usually slow cycling Able to give rise to at least one differentiated, somatic, cell type.

  2. Somatic Cell Terminally differentiated cells Some limited proliferative capability- e.g. Transit amplifying cell.

  3. Classification of Stem Cells • Totipotent: • e.g. Blastomeres of early embryo. • Able to give rise to all cell types of the body

  4. Classification of Stem Cells Pluripotent: • e.g. Inner Cell Mass of blastocyst (-source of embryonic stem cells-ES). • Able to give rise to all cell types found in the embryo and adult • But not Placenta

  5. Classification of Stem Cells • Multipotent • Able to give rise to more than one differentiated cell type. • E.g.Haematopoietic stem cells of bone marrow. • Adult stem cells?

  6. Classification of Stem Cells • Totipotent • Able to give rise to one cell type • e.g. primordial germ cells of gonads - gametes.

  7. Historical concepts of stem and somatic cells. • Potency • Embryonic SC pluripotent • Adult SC multipotent e.g. blood, Skin, neuronal etc • Somatic progenitor cells limited to specific differentiation pathways • Somatic cells are programmed and cannot de-differentiate i.e once a skin cell always a skin cell

  8. Embryonic Stem Cells Embryonal carcinoma (EC) cells • Derived from Teratocarcinomas: • Complex tumours – contain a mix of un-differentiated stem cells and differentiated cell types • EC cells also made by placing blastocysts at ectopic sites • Led to in vitro culture of ES cells

  9. Embryonic Stem Cells • Embryonic Stem Cells • Derived from inner cell mass of blastocyst • Express Oct4 • LIF in culture medium maintains them in undifferentiated state

  10. In vitro differentiation of ES cells Removal of LIF and ES differentiate into a mass of different cell types :- • Hepatic • Muscle • Haematopoietic • Epithelial • Neuronal Pure cell populations can be obtained from ES

  11. Adult Stem Cells • Adult stem cells occupy unique niches • Epidermis and hair follicle • Intestinal epithelium • Brain • Haematopoietic system

  12. Niche is important • Destroy niche destroy stem cells • Can be re-populated • Gut • Skin • Brain • Bone marrow

  13. Plasticity of Somatic and Stem Cells Dolly Cloning of the ewe ‘Dolly’ showed that the nucleus of an adult cell could be re-programmed in the confines of an enucleated-fertilised-oocyte.

  14. Plasticity of Somatic and Stem Cells • Some nuclei can be genetically re-programmed without separating the nuclei from the cytoplasm e.g. • Adult, GFP labelled, bone marrow cells from adult mouse injected into ICM of blastocyst • Tracing of subsequent cell lineages showed adult cells re-programmed to express foetal globin genes

  15. Plasticity of Somatic and Stem Cells • Bone marrow stromal cells from adult male mice (XY) • Injected into lethally irradiated female recipient mice • Male cells (XY) found in Bone, cartilage, Lung of female. • Also in regenerating liver following hepatic damage.

  16. Plasticity of Somatic and Stem CellsTransdifferentiation • Ability of an adult stem cell to acquire a broader differentiation potential • GFP labelled bone marrow cells-injected into lethally irradiated mice • GFP cells found in many tissues • Suggests: neuronal and haematopoietic stem cells can generate – liver, lung, muscle and intestinal cells ???????????????

  17. Plasticity of Somatic and Stem CellsTransdifferentiation • Stem cells from adult mouse hair follicles (GFP labelled)-Injected into blastocyst- • GFP labelled cells in many organs of developing embryos

  18. Plasticity of Somatic and Stem CellsTransdifferentiation • Mesenchymal cells from adult hair follicles can be stimulated down osteogenic, blood and adipocyte lineages

  19. Cell Fusion Causes Confusion • However, are they functional • In vitro studies suggest cell fusion may occur

  20. Future Questions • .Function of trans-differentiated cells. • .Trans-differentiation versus de-differentiation. • .Understanding the stem cell niche • .Tissue engineering • Cancer stem cells

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