Stem Cell Research and Developmental Biology

MRC Centre for Developmental and Biomedical Geneticsand

Dept of Biomedical Science

• 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

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

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

Can use animal models: development conserved (tissue and cell types; pathways that define discrete cell types)

Key aim: to understand the balance between cell division and differentiation

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

• 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

Inner cell mass:origin of ‘es cells’

Es cells: in vitro can self-renew indefinitely, or differentiate to many fates

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

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

•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

Haematopoetic system: original definition of stem cell:

indefinite self-renewal; complete cellular reconstitution

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

Some questions:

Can regeneration occur in the absence of ‘stem cells’ (self-renewing, multi-potent cells)?

Can we identify adult ‘stem cells’ ?

4 factors(Yamanaka;2006, 2007)

Portfolio of activities

• Description of stem cells

• Description of self-renewal versus differentiation pathways

• Directed differentiation of stem cells.

And finally…..

• Tests for integrity and function of es-derived cells