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Emergence of Patterned Stem Cell Differentiation Within Multicellular 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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embryonic stem cells adult stem cells
Introduction embryonic stem cells adult stem cells Properties Self-renewal Potency embryonic stem cells that are isolated from the inner cell mass of blastocysts, and adult stem cells that are found in adult tissues. In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin or intestinal tissues Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[4] Totipotent (a.k.a omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable, organism.[4] These cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.[citation needed] Pluripotent stem cells are the descendants of totipotent cells and can differentiate into nearly all cells,[4] i.e. cells derived from any of the three germ layers.[5] Multipotent stem cells can differentiate into a number of cells, but only those of a closely related family of cells.[4] Oligopotent stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cells.[4] Unipotent cells can produce only one cell type, their own,[4] but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells). . 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 receptor–ligand 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, Young’s modulus,moment of inertia, length, and resulting deflection of the post,respectively
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Blebbistatin Y inhibitor of the Rho-associated protein kinase ML-7 myosin light chain kinase (MLCK) inhibitor Blebbistatin preferentially binds to the ATPase intermediate with ADP and phosphate bound at the active site
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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. Understanding how fate decisions are tied to tissue form will provide a better appreciation of how cells orchestrate morphogenetic processes, as well as a roadmap for directing stem cell fates in regenerative therapies.
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References 1, Stem cells 2008; 26:2921-2927 2, Cell 2006; 126:677-689
3, Nature Reviews 2006; 7: 4, Development 2003; 130: 5, PNAS 2003; 100:
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