{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/39905"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/39905","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"The roll of integrins in hematopoiesis","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Eshghi, Shawdee"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Biological Engineering Division.","school":null,"contributors":[],"advisors":["Linda G. Griffith."],"committee_chairs":[],"committee_members":[],"year":2007,"date_issued":"2007","date_published":"2007","updated_at":"2026-07-22T22:22:04Z","subjects":["Biological Engineering Division."],"languages":["eng"],"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."],"rights_urls":["http://dspace.mit.edu/handle/1721.1/39905","http://dspace.mit.edu/handle/1721.1/7582"],"identifier_entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://dspace.mit.edu/handle/1721.1/39905"],"render_values":[{"text":"http://dspace.mit.edu/handle/1721.1/39905","href":"http://dspace.mit.edu/handle/1721.1/39905","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/1721.1/39905","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Linda G. Griffith."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. Biological Engineering Division."]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Massachusetts Institute of Technology. Biological Engineering Division."]},{"key":"dc:creator","label":"Author","values":["Eshghi, Shawdee"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2009-01-23T14:51:54Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2009-01-23T14:51:54Z"]},{"key":"dc:date.issued","label":"Date","values":["2007"]},{"key":"dc:publisher","label":"Institution","values":["Massachusetts Institute of Technology"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biological Engineering Division."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["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."]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://dspace.mit.edu/handle/1721.1/39905","http://dspace.mit.edu/handle/1721.1/7582"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://dspace.mit.edu/handle/1721.1/39905","http://hdl.handle.net/1721.1/39905"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007.","Includes bibliographical references (p. 113-123)."]},{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["The roll of integrins in hematopoiesis"]}]}],"canonical_facts":{"dc:contributor.advisor":["Linda G. Griffith."],"dc:contributor.department":["Massachusetts Institute of Technology. Biological Engineering Division."],"dc:contributor.other":["Massachusetts Institute of Technology. Biological Engineering Division."],"dc:creator":["Eshghi, Shawdee"],"dc:date.accessioned":["2009-01-23T14:51:54Z"],"dc:date.available":["2009-01-23T14:51:54Z"],"dc:date.issued":["2007"],"dc:description":["Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007.","Includes bibliographical references (p. 113-123)."],"dc:description.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."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["http://dspace.mit.edu/handle/1721.1/39905","http://hdl.handle.net/1721.1/39905"],"dc:language.iso":["eng"],"dc:publisher":["Massachusetts Institute of Technology"],"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."],"dc:rights.uri":["http://dspace.mit.edu/handle/1721.1/39905","http://dspace.mit.edu/handle/1721.1/7582"],"dc:subject":["Biological Engineering Division."],"dc:title":["The roll of integrins in hematopoiesis"],"dc:type":["Thesis"]},"updated_at":"2026-07-22T22:22:04Z"}