Human hematopoietic stem cells in aging and myelodysplastic syndrome

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Abstract/Contents

Abstract
Although there have been extensive studies on the changes to the mouse hematopoietic system and the hematopoietic stem and progenitor cells during aging, this has not been as carefully looked at in humans. Understanding the changes in the human hematopoietic system that occur during normal aging will naturally be the basis of comparison for understanding the changes that occur in age-associated hematopoietic diseases, including anemia, myelodysplastic syndrome, and leukemia. In this dissertation, we provide evidence to suggest that, with age, human hematopoietic stem cells (HSC) increase in frequency and preferentially generate cells of the myeloid lineage, as opposed to the lymphoid lineage. This may be one of the reasons that myeloid disorders, such as those mentioned earlier, are common in the elderly population. In order to better characterize the cellular and molecular changes that occur in as well as mechanisms that may contribute to the pathogenesis of myelodysplastic syndrome (MDS), we compared hematopoietic stem and progenitor cell populations from MDS patients to those from healthy elderly individuals. We found that granulocyte-macrophage progenitors in the bone marrow were significantly reduced in MDS, reduction of ribosomal protein S6 in HSC causes an MDS-like phenotype, and cell surface markers can be to distinguish and separate HSC that are capable of normal hematopoiesis from HSC that are responsible for causing MDS. Collectively, the data from these experiments suggest that MDS is a disease that originates in HSC, and curing the disease will require the elimination of the MDS HSC.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2011
Issuance monographic
Language English

Creators/Contributors

Associated with Pang, Wendy W
Associated with Stanford University, Program in Cancer Biology.
Primary advisor Weissman, Irving L
Thesis advisor Weissman, Irving L
Thesis advisor Greenberg, Peter
Thesis advisor Majeti, Ravindra, 1972-
Thesis advisor Mitchell, Beverly S
Thesis advisor Schrier, Stanley L
Advisor Greenberg, Peter
Advisor Majeti, Ravindra, 1972-
Advisor Mitchell, Beverly S
Advisor Schrier, Stanley L

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Wendy Wan-Kiu Pang.
Note Submitted to the Program in Cancer Biology.
Thesis Ph.D. Stanford University 2011
Location electronic resource

Access conditions

Copyright
© 2011 by Wendy W. Pang
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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