Cell Differentiation and Specialisation
Development: Process by which single cell develops into a mature organism
Embryogenesis: Converts genotype into adult phenotype, passing through series of
morphologically complex embryological and larval forms – Anatonomical variation (basis
of evolution) is generated by modifying embryogenesis
Embryonic development begins at fertilisation
haploid egg + haploid sperm = diploid genome
Once activated, development follows clearly
defined steps that can be recognised
1. Cleavage: period of rapid cell divisions – large
egg is divided into smaller cell, generates a ball
of cells (blastula surrounding fluid filled cavity
blastocoel)
2. Gastrulation: phase coordinated cell movements
that generate multi-layered structure of embryo
3 main types of movement:
Invagination (infolding of blastula to form archenteron)
Involution (inward movement of previously external layer so it spreads over internal
surface of remaining external layer, eg. amphibians)
Ingression (migration of individual cells from surface epithelium into interior of
embryo, can migrate with similar mesenchymal cells. eg. mice, chicks cells ingress as
specialised structure “primitive streak”)
Ectoderm (Outer) Mesoderm (Middle) Endoderm (Inner)
Digestive tract Cardiac muscle cells Brain neurons
Respiratory tract Skeletal muscle cells Spinal Cord
(alveolar cells) RBC Epidermal skin cells
Liver Tubule cells of kidney Hair, Nails
Gall Bladder Smooth muscle cells (gut) Pigment cells
Pancreas + Urinary bladder Cartilage
Thyroid cells Bone
Connective Tissues
Blood vessels
Gonads
Germ Layer: egg + sperm
, Cells become more specialised (lineage restricted) – restricts the types of cells
they can generate
Zygote Blastula Gastrula Ectoderm + Mesoderm + Endoderm
Ectoderm Epidermis and associated structures (skin, hair, nails) + Brain and
Nervous system
Mesoderm Notochord + Somites (Muscle + Excretory System + Gonads + Outer
covering of internal organs) + Mesenchyme – loose migratory cells (Dermis +
Circulatory system + Bones + Cartilage)
Endoderm Embryonic Gut Inner lining of digestive tract + inner lining of
respiratory tract + Glands (liver and pancreas etc.)
Tissue Generation
Cell types are not pre-formed in egg
- Formed by epigenesist (complexity increasing at each step of developmental
process)
- Progressive series of developmental decisions narrowing options of cells from
totipotent pluripotent/multipotent unipotent
- Main mechanism for reducing potency = embryonic induction
- Cell signalling allows cells to make a choice between no. of alternative cell types
2 steps recognised in cell commitment to form specific cell type
Specification: commitment to particular fate, changed in particular circumstances
Determination: commitment to particular fate – not changeable
Differentiation
Haploid human genome: ~20 000 functional, protein coding genes (“pseudogenes”:
non-functional, but some can have altered functions
6-7% transcribed by all cells housekeeping genes (eg. metabolism, cell cycle
control, RNA+protein synthesis)
Cell transformation by transcription factors
Weintraub made cDNA copies from mRNA of genes transcribed in skeletal muscle
cells
Genes individually placed under viral control promoter and transfected in cultured
fibroblasts
One of the genes transformed fibroblasts -> myoblasts (encoded basic helix loop
helix transcription factor MyoD) – similar results for Myf5, Myf6, Myog
Single gene could reverse differentiation programme of a fibroblast and activate
programme for muscle
, Takahashi and Yamanaka use transcription factors to return fibroblasts to
pluripotent state
Chose 24 transcription factors associated with pluripotency in mammalian embryos
and mouse embryonic stem cells combining 4 genes (Oct3/4. Sox2, c-Myc, Klf4)
sufficient to induce pluripotency
Expression of 4 genes transformed <1% of fibroblasts – transformed cells were
pluripotent (iPSC – induced pluripotent stem cells)
iPSCs also made from human fibroblasts
Classification of Stem Cells
Totipotent
Can generate all embryonic and extra-embryonic
tissues (placenta)
Pluripotent
Can generate all embryonic tissues
Multipotent
Can produce multiple cell types within related tissues
but not whole embryo
Persist in the adult
Responsible for growth, maintenance and
regeneration throughout life
Tissue formation occurs via a cellular hierarchy – rare stem cells produce transit-
amplifying cells (progenitors)
Progenitors proliferate and differentiate to form many mature cells
Terminally differentiated cells are lost/used up and need to be replaced
Stem cells produce trillions of cells per day – eg. 1 trillion cells/day from bone
marrow
Stem cell pool would be very quickly used up during development/homeostasis but
the stem cell pool is maintained by:
Self-renewal: stem cell division that produces an undifferentiated copy of a stem
cell
Symmetrical: produces 2 identical daughter stem cells – is thought to occur during
expansion of stem cells (development/infection etc.)
Asymmetrical: produces 1 stem cell and 1 more differentiated daughter cell –
though to occur during normal tissue maintenance in adults
What is a stem cell vs. what makes a cell specialised?
Stem Cell “Specialised” Cell
Development: Process by which single cell develops into a mature organism
Embryogenesis: Converts genotype into adult phenotype, passing through series of
morphologically complex embryological and larval forms – Anatonomical variation (basis
of evolution) is generated by modifying embryogenesis
Embryonic development begins at fertilisation
haploid egg + haploid sperm = diploid genome
Once activated, development follows clearly
defined steps that can be recognised
1. Cleavage: period of rapid cell divisions – large
egg is divided into smaller cell, generates a ball
of cells (blastula surrounding fluid filled cavity
blastocoel)
2. Gastrulation: phase coordinated cell movements
that generate multi-layered structure of embryo
3 main types of movement:
Invagination (infolding of blastula to form archenteron)
Involution (inward movement of previously external layer so it spreads over internal
surface of remaining external layer, eg. amphibians)
Ingression (migration of individual cells from surface epithelium into interior of
embryo, can migrate with similar mesenchymal cells. eg. mice, chicks cells ingress as
specialised structure “primitive streak”)
Ectoderm (Outer) Mesoderm (Middle) Endoderm (Inner)
Digestive tract Cardiac muscle cells Brain neurons
Respiratory tract Skeletal muscle cells Spinal Cord
(alveolar cells) RBC Epidermal skin cells
Liver Tubule cells of kidney Hair, Nails
Gall Bladder Smooth muscle cells (gut) Pigment cells
Pancreas + Urinary bladder Cartilage
Thyroid cells Bone
Connective Tissues
Blood vessels
Gonads
Germ Layer: egg + sperm
, Cells become more specialised (lineage restricted) – restricts the types of cells
they can generate
Zygote Blastula Gastrula Ectoderm + Mesoderm + Endoderm
Ectoderm Epidermis and associated structures (skin, hair, nails) + Brain and
Nervous system
Mesoderm Notochord + Somites (Muscle + Excretory System + Gonads + Outer
covering of internal organs) + Mesenchyme – loose migratory cells (Dermis +
Circulatory system + Bones + Cartilage)
Endoderm Embryonic Gut Inner lining of digestive tract + inner lining of
respiratory tract + Glands (liver and pancreas etc.)
Tissue Generation
Cell types are not pre-formed in egg
- Formed by epigenesist (complexity increasing at each step of developmental
process)
- Progressive series of developmental decisions narrowing options of cells from
totipotent pluripotent/multipotent unipotent
- Main mechanism for reducing potency = embryonic induction
- Cell signalling allows cells to make a choice between no. of alternative cell types
2 steps recognised in cell commitment to form specific cell type
Specification: commitment to particular fate, changed in particular circumstances
Determination: commitment to particular fate – not changeable
Differentiation
Haploid human genome: ~20 000 functional, protein coding genes (“pseudogenes”:
non-functional, but some can have altered functions
6-7% transcribed by all cells housekeeping genes (eg. metabolism, cell cycle
control, RNA+protein synthesis)
Cell transformation by transcription factors
Weintraub made cDNA copies from mRNA of genes transcribed in skeletal muscle
cells
Genes individually placed under viral control promoter and transfected in cultured
fibroblasts
One of the genes transformed fibroblasts -> myoblasts (encoded basic helix loop
helix transcription factor MyoD) – similar results for Myf5, Myf6, Myog
Single gene could reverse differentiation programme of a fibroblast and activate
programme for muscle
, Takahashi and Yamanaka use transcription factors to return fibroblasts to
pluripotent state
Chose 24 transcription factors associated with pluripotency in mammalian embryos
and mouse embryonic stem cells combining 4 genes (Oct3/4. Sox2, c-Myc, Klf4)
sufficient to induce pluripotency
Expression of 4 genes transformed <1% of fibroblasts – transformed cells were
pluripotent (iPSC – induced pluripotent stem cells)
iPSCs also made from human fibroblasts
Classification of Stem Cells
Totipotent
Can generate all embryonic and extra-embryonic
tissues (placenta)
Pluripotent
Can generate all embryonic tissues
Multipotent
Can produce multiple cell types within related tissues
but not whole embryo
Persist in the adult
Responsible for growth, maintenance and
regeneration throughout life
Tissue formation occurs via a cellular hierarchy – rare stem cells produce transit-
amplifying cells (progenitors)
Progenitors proliferate and differentiate to form many mature cells
Terminally differentiated cells are lost/used up and need to be replaced
Stem cells produce trillions of cells per day – eg. 1 trillion cells/day from bone
marrow
Stem cell pool would be very quickly used up during development/homeostasis but
the stem cell pool is maintained by:
Self-renewal: stem cell division that produces an undifferentiated copy of a stem
cell
Symmetrical: produces 2 identical daughter stem cells – is thought to occur during
expansion of stem cells (development/infection etc.)
Asymmetrical: produces 1 stem cell and 1 more differentiated daughter cell –
though to occur during normal tissue maintenance in adults
What is a stem cell vs. what makes a cell specialised?
Stem Cell “Specialised” Cell
