Guided differentiation of ES cell into mesenchymal stem cell
What Are Cell Differentiation and Cell Specification?
Transcript of What Are Cell Differentiation and Cell Specification?
What Are Cell Differentiation
and Cell Specification?
• Development of differentiated cell types
– different in function, cell shape, internal
structures, proteins and biochemical pathways
• Preceded by commitment to fate
– Specification: can differentiate in neutral
environment, but reversible in new
environment
– Determination: irreversible even in new
environment
What Are the Different Modes of
Specification?
• Autonomous Specification
– Independent of other cells in embryo (self-
differentiating parts)
– Determined by internal cytoplasmic factors
– If cleavage patterns are invariant, then cell fates will be invariant
– “Mosaic” development
– Characteristic of invertebrates
What Are the Different Modes of
Specification?
• Conditional Specification (“Non-Autonomous”)
– Depends on conditions (cell interactions)
– More variable (variations in which cells are assigned which fates)
– Capacity to “regulate”
– Characteristic of vertebrates (and some invertebrates)
What Are the Different Modes of
Specification?
• Syncitial Specification
– Interactions between regions of cells before
cellularization
– Cells have no specific cell fate before cellularization
– After cellularization, mostly conditional specification
– Most insects
Chabry’s Experiment 1887
• Mollusc
• Certain cells
form trochoblasts
(ciliated)
• In isolation
• autonomous
Roux’s Frog Cell Destruction
Experiments (1888)
• Defect experiment
• Frog embryos
• One blastomere makes
only half of embryo
• Support for
autonomous
specification?
Tunicate Specification is Mostly
Autonomous
• Tunicate embryo
– Isolation experiment
– Separate 8 cell stage
quadrants
– Each forms only what
it would have formed
and does so
autonomously
Cytoplasm Contains Determinants
Cytoplasmic Autonomy Extends
to the Molecular Level
• Tunicate Embryo
(1977)
– Isolated muscle forming cell lineage makes muscle acetylcholinesterase
– If cytoplasm injected into isolated b4.2 causes it to make the enzyme
Driesch’s Sea Urchin Isolation
Experiments: Regulation (1892)
• Sea urchin
• Each blastomere gives rise to complete larva
• Supports conditional specification
Conditional Specification in Frog
Transplantation Experiment
• Cell fate according to
new environment (A)
– fate not fixed
• Embryo makes up for
what was taken away
(B)
– regulation
Gradient of Fate-Determining
Molecules in a Syncytial Embryo
Stem Cells and Commitment
• Cells that divide to form one copy of itself and one different
– Pluripotent stem cells can lead to many cell types
– Committed stem cells can lead to fewer types
– Progenitor cells committed to one or few cell fates: not stem cells
• Early cells have most potential (embryonic, fetal)
Restriction of Potency with Time
• Committed cells usually don’t change in
new environment
• Blood cell lineage:
Mutants Identify Some Fate-
determining Molecules
• What would be effect of a mutation in a
fate-determining molecule?
• These molecules must be acting very early – Packaged by the mother
– Mutation in gene will influence the mother’s ability to
make viable embryos
– “Maternal-effect” genes