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. Stem Cell

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

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

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

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?

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

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

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

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

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

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

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

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.

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

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.

Plasticity of Somatic and Stem Cells Transdifferentiation 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 ???????????????

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

Plasticity of Somatic and Stem Cells Transdifferentiation Mesenchymal cells from adult hair follicles can be stimulated down osteogenic, blood and adipocyte lineages

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

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