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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.
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 cellsES).
•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
• 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 reprogrammed 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 cellsinjected 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