The roll of integrins in hematopoiesis

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Eshghi, Shawdee

Advisor dc:contributor.advisor

• Linda G. Griffith.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/39905
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/39905

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/39905