Emergence of Patterned Stem Cell Differentiation Within Multicellular Structures

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Emergence of Patterned Stem Cell Differentiation
WithinMulticellular Structures
Tongcheng Qian April 27th, 2009
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Outline

• Introduction
• Emergence of patterned stem cell
• differentiation within multicellular structures
• Summary

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Introduction

• embryonic stem cells
• adult stem cells

Properties Self-renewal Potency

• Totipotent
• Pluripotent
• Multipotent
• Oligopotent
• Unipotent

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Morphogenis

• Spatial gradients of diffusible factors known as
  morphogens
• Mechanical force

mechanical stiffness of the local tissue
environment
contractile activity of the cells
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How the mechanical force affect the cells
The example shows the dramatic difference in
morphology that the same cells will assume after
only 4 hours in different matrices
Cellular mechanics involves three steps
mechanosensing, mechanotransduction
mechanoresponse.
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Mechanisms of force sensing
gain or loss of binding sites
mechanosensitive ion channels can be regulated
by membrane tension
receptorligand bonds
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Matrix Elasticity Directs Stem Cell Lineage
Specification
Tissue elasticity and differentiation of naive
MSCs Differnet stiffness of the matrices that
mimic different tissues can lead the MSCs
differentiate into relevant cell lineage
respectively
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Emergence of patterned stem cell differentiation
within multicellular structures
Patterned stem cell on a flat surface
Staining ALP, Fast Blue RR cbfa-1
Lipid droplets, oil red O PPAR r
Nuclei, DAPI
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Different patterned size
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Different patterned shape
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where F, E, I, L, and delta are the bending
force, Youngs modulus,moment of inertia, length,
and resulting deflection of the post,respectively
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(No Transcript)
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Blebbistatin Y-27632 inhibitor of the
Rho-associated protein kinase ML-7 myosin
light chain kinase (MLCK) inhibitor
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• All the patterned MSCs in low force
• distribution area will differentiate into
• adipocytes, whereas MSCs in high force
• distributed area will differentiate into
• ostogenic cells, this happens in two
• dimensional surface, and what about three
• dimensional patterned cells?

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Patterning of differentiation in
three-dimensional structure
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Summary

• The specification and differentiation of stem
  cells
• can be mostly decided by the diffusible signals
• and mechanical force.
• The mechanical force finally converted into
• biochemical signals.
• To understand the mechanisms can be very
• helpful for solving many problems.

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References

• 1, Stem cells 2008 262921-2927
• 2, Cell 2006 126677-689
• 3, Nature Reviews 2006 7265-275
• 4, Development 2003 1302027-2037
• 5, PNAS 2003 1001484-1489