The roll of integrins in hematopoiesis
Name
182574117-MIT.pdf
Description
Full printable version
Size
9 MB
Format
Adobe PDF
Checksum (MD5)
84e388de565ce74aa64289a1af463835
Author(s)
Eshghi, Shawdee
Advisor(s)
Linda G. Griffith.
Date Issued
2007
Publisher
Massachusetts Institute of Technology
Abstract
Hematopoietic stem cells (HSCs) hold great promise for the treatment of disease. The rare frequency at which HSCs occur in the bone marrow under homeostatic conditions is a limiting factor in both their study and clinical use. ex vivo expansion of these cells is therefore a necessary step to maximizing their potential. In this thesis I explore the concept that signals from the extracellular matrix can direct differentiation, survival and self-renewal decisions in hematopoietic cells, and thus can provide a foundation for the design of ex vivo expansion strategies. This work is focused on the role integrins, the major class of cell-extracellular matrix adhesion molecules, play in mediating these signals to hematopoietic cells at two developmental stages. In the erythroid lineage, I show that expansion of committed erythroid progenitors is regulated by growth factor and integrin-mediated signals in temporally distinct regimes. I establish a biologically relevant role for [alpha]401 but not [alpha]501 integrins in erythropoiesis and provide evidence that erythroid differentiation and expansion are regulated by separate processes.
(cont.) In the study of uncommitted HSCs, I identify several integrin subunits that are differentially expressed on highly purified HSC populations that correlate with long term repopulating ability. One of these subunits, [alpha]2 integrin, specifically mediates adhesion of HSCs to bone marrow extracellular matrix proteins, thereby providing a potential mechanism for stem cell self-renewal. This work establishes that integrin-mediated interactions between hematopoietic cells and the extracellular matrix are dynamic and provide important developmental cues.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007.
Includes bibliographical references (p. 113-123).
Subjects
Biological Engineering Division.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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