LW-BCH4122-Lecture2_2009

LW-BCH4122-Lecture2_2009 - Stem Cells Lisheng WANG...

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Stem Cells Lisheng WANG lwang@uottawa.ca Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa
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Lecture 2: Introduction of Stem Cells (Part II) What are stem cells Types of stem cells Some general concepts of stem cells
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Some General Concepts of Stem Cells Stem cell fate Stem cell niche and environment Clonality Symmetric or asymmetric cell division to make a dual role of self-renewal and differentiation Cancer initiating/stem cells Stem cell and aging Epigenetic (reprogramming)
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Stem cell fate dedifferentiation
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Example of transdifferentiation (plasticity) (blood) stem cells Liver Neuron Muscle
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Stem cell niche and environment Stem cell Niche Tissue Systemic milieu External environment
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Stem cell Nature 441, 1075-1079 (29 June 2006) Stem cell niche and environment Cell-cell contact, •Cell-extracellular matrix contact •Autocrine, paracrine and endocrine Structural and physical effects •Neural regulation (endocrine)
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Example: Physical factors control cell fate Cell 2006; 126:645-647 & 677-689
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Clonality It is crucial to know whether a single cell is capable of developing an array of cell types (clonality), or whether multiple stem cell types, when grown together, are capable of forming multiple cell types. For instance, recent research has shown that a mixture of cells removed from fat tissue or umbilical cord blood are capable of developing into blood cells, bone cells, and perhaps others. However, Researchers have not shown that a single cell is responsible for giving rise to other cell types or, if so, what kind of cell it is.
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Symmtric or asymmtric cell division – stem cell strategies to accomplish dual task of self-renewal and generation of differentiated cells Orange: stem cells; Green: differentiated cells (Nature 2006; 441:1068-1074)
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Stem cells can facultatively use both symmetric and asymmetric divisions Nature 441 , 1068-1074 (29 June 2006)
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Sean J. Morrison & Judith Kimble Nature 441 , 1068-1074 (29 June 2006) Possible controls of asymmetric stem-cell division Asymmetric localization of cell polarity regulators Segregation of cell fate determinants (red) to the cytoplasm Regulated orientation of the mitotic spindle retains only one daughter in the stem-cell niche (red) - Only daughter stem cells access to extrinsic signals
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(Nature 2006;442:17-18) (Cancer Cell 2006;10: 257-268) Cell Stem Cell 1, 313–323 (2007) Cancer stem cell hypothesis
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Leukemia – direct evidence for cancer stem cells 1961: New tumors grow after implanting >10 6 cells Terminal cancer patients subcutaneously injected with graded numbers of autologous tumor cells!
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LW-BCH4122-Lecture2_2009 - Stem Cells Lisheng WANG...

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