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LW-BCH4122-Lecture2_2011Sep

LW-BCH4122-Lecture2_2011Sep - Stem Cells Lisheng WANG...

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Stem Cells Lisheng WANG [email protected] 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) Hematopoietic (blood) stem cells Liver Neuron Muscle
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Stem cell Nature 441, 1075-1079 (29 June 2006) J Biomech. 2010 Jan 5;43(1):55-62 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 Science 2010 AUGUST 27; 329: 1078. Cell 2006; 126:645-647 & 677-689 Substrate elasticity is a potent regulator of MuSC fate in culture. During first week in culutre, soluble induction factors reprogram mesenchymal cells to specific lineages. After several weeks in culutre, the cells commitment to a lineage is specified by matrix elasticity.
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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. Genes Dev. 2009; 23:2675-2699)
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Stem cells can facultatively use both symmetric and asymmetric divisions (Nature 2006; 441:1068-1074. Genes Dev. 2009; 23:2675-2699) Early Embryonic Dev’t Late embryonic dev’t and healthy adult maintenance Symmetric and assymetric requried after injury Too much symetric= tumorigenesis Too much assymetric= reduced tissue repair
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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 for maintaining stem cell identity (b)Cell fate determinants: proteins and mRNA that can be associated with membrane, centrosome or cellular compoent (a) Polarity regulators: Proteins/lipids plasma membrane
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