Developmental biology: a brief introduction to development, and to the use of animal model systems
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Stem Cell Research and Developmental Biology
MRC Centre for Developmental and Biomedical Geneticsand
Dept of Biomedical Science
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• Developmental biology: a brief introduction to development, and to the use of animal model systems
• Impact of developmental biology on Stem Cell Research:
– Derivation, Differentiation and Identification of ‘es cells’
– Definition of other types of ‘stem cell’
– Animal models as test-beds for transplantation
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Developmental Biologists: use animal models to understand how we develop into a functional organism.
A key aim: to identify particular cell types and elucidate the cellular and molecular pathways that regulate organ
and tissue formation
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Muscle cell differentiation/ Musculoskeletal disease:
Neuronal differentiationNeurodegenerative diseases
Tools available thatdefine discrete cell types(shown by the different colours)
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Modelling arteriogenesis using the zebrafish
Ingham/Chico/Crossman
Tools increasingly sophisticated: allow imaging of discrete cells in real time in vivo
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Can use animal models: development conserved (tissue and cell types; pathways that define discrete cell types)
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Key aim: to understand the balance between cell division and differentiation
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differentiationcleavagetissue allocation
totipotent
committedpluripotent
gastrulation
multipotent
self renewal
1. Detailed understanding of the specification and differentiationof cellular systems (neuronal, musculoskeletal, vascular)2. Balance between proliferation (self renewal) and differentiation
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• Developmental biology: a brief introduction to development, and to the use of animal model systems
• Impact of developmental biology on Stem Cell Research:
– Derivation, Differentiation and Identification of ‘es cells’
– Definition of other types of ‘stem cell’
– Animal models as test-beds for transplantation
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Inner cell mass:origin of ‘es cells’
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Es cells: in vitro can self-renew indefinitely, or differentiate to many fates
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Impacts of developmental biology:• Characterisation of inner cell mass and es cells• Understanding of cell types present (using ‘markers’)• Understanding of pathways that regulate self-renewal and differentiation
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Points to note:
• No single marker exists that defines a stem cell
• Proliferating es cells in vitro are an artefact: in vivo, cells of the inner cell mass will go on to finely balance proliferation and differentiation, to build an organism
• Mouse and human es cells: key differences
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•Derivation, Differentiation and Identification of ‘es cells’
•Definition of other types of ‘stem cell’
•Derivation, Differentiation and Identification of ‘es cells’
•Definition of other types of ‘stem cell’
Emerged from studies of haematopoeisis (initially) and more recently through developmental biology studies that analyse the origins of tissue and organ progenitors
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Haematopoetic system: original definition of stem cell:
indefinite self-renewal; complete cellular reconstitution
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Other sites whererenewal necessaryinto adulthood include:SkinGutMuscle
Clear signs of new cellproduction in adults inother regions including:Brain
Question: are there ‘stem cells’ present in these locations?
Defining experiments havenot been performed
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Some questions:
Can regeneration occur in the absence of ‘stem cells’ (self-renewing, multi-potent cells)?
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Can we identify adult ‘stem cells’ ?
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4 factors(Yamanaka;2006, 2007)
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Portfolio of activities
• Description of stem cells
• Description of self-renewal versus differentiation pathways
• Directed differentiation of stem cells.
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And finally…..
• Tests for integrity and function of es-derived cells