Krause lecture notes

Krause lecture notes - Hematopoiesis blood cell formation...

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Hematopoiesis - blood cell formation •occurs throughout life and is highly regulated in order to respond to a variety of conditions •A single type of progenitor cell, the Hematopoietic Stem Cell (HSC), gives rise to all terminally differentiated cells of the blood (MBOC 22-30) Multipotent stem cell •LTR - long term repopulation ability (after >5-6 months) •capable of self renewal •STR - short term repopulation ability (a few weeks) •still multipotent but have lost ability to produce long- lived stem cells •HSCs with LTR are rare • (1 in 10 5 marrow cells)
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Stem cells occupy a "niche" •A niche is a small zone of cells and extracellular substrates that maintain stem cells and control their activity •HSC niche - is where ? •similarly, ES (embryonic stem) cells have to be grown on feeder layers of mitotically inactive Fbroblasts •feeder cells are critical to maintaining ES in an undifferentiated state •presumably, feeder cells produce factors that suppress differentiation or promote self renewal •e.g., Leukemia inhibitory factor (LI±) promotes murine ES cell survival and growth and can replace feeder cells •response to LI± is mediated by the MAP kinase pathway •Human ES cells are not supported by LI± •Human ES cells require feeder layer •What is the role of the microenvironment (niche) in maintaining a stem cell?
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A. Major Questions •What is the developmental potential of adult stem cells? •SpeciFcally, what is the developmental potential of a hematopoietic stem cell (HSC) •What is the phenotype of a HSC, and how can it be found and identiFed? •Look in its niche! B. Hypotheses •A single HSC can differentiate into all hematopoietic lineages •LTR an irradiated mouse •A single HSC can self-renew •give rise to another HSC •assayed by serial transplantation •A single HSC can differentiate into non-hematopoietic lineages - transdifferentiation? •epithelial lineages (most epithelia examined in this paper are of endodermal origin)
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This note was uploaded on 10/19/2009 for the course B M B 460 taught by Professor Hanna-rose,w during the Spring '08 term at Penn State.

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Krause lecture notes - Hematopoiesis blood cell formation...

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