Purifiation and characterization of the in vivo behvoirs of natural killer cell progenitors and hematopoietic stem cells

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Abstract/Contents

Abstract
Hematopoietic stem cells (HSC) are at the top of hematopoietic hierarchy and give rise to functional effector cells through a succession of increasingly committed downstream progenitor cells. Based upon data obtained from transplantation and in vitro culture experiments we have constructed a model of hematopoietic development by which small numbers of HSCs generate large numbers of mature effector cells through the successive amplification of transiently proliferating progenitor cells downstream of HSCs. HSCs have been extensively characterized based on their cell surface phenotype and functional activities during transplantation assays. Here we describe a marker, CD11a, which allows for the enhanced purification of murine HSCs. We have shown that upregulation of CD11a on HSCs denotes the loss of self-renewal potential, and that CD11a-Slam+CD34-c-kit+Sca1+Lin- are the true HSC. Natural killer (NK) cells develop in the bone marrow and are known to gradually acquire the ability to eliminate infected and malignant cells, yet the cellular stages of NK lineage commitment and maturation are incompletely understood. Using 12-color flow cytometry, we identified a novel NK-committed progenitor (pre-NKP) that is a developmental intermediate between the upstream common lymphoid progenitor (CLP) and the downstream NKP, previously assumed to represent the first stage of NK lineage commitment. Taken together, our data provide a high-resolution in vivo analysis of the earliest steps of NK cell commitment and maturation.

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 Fathman, John Warner
Associated with Stanford University, Program in Immunology.
Primary advisor Weissman, Irving L
Thesis advisor Weissman, Irving L
Thesis advisor Negrin, Robert S
Thesis advisor Shizuru, Judith Anne
Thesis advisor Sunwoo, John B
Advisor Negrin, Robert S
Advisor Shizuru, Judith Anne
Advisor Sunwoo, John B

Subjects

Genre Theses

Bibliographic information

Statement of responsibility John Warner Fathman.
Note Submitted to the Program in Immunology.
Thesis Thesis (Ph. D.)--Stanford University, 2011.
Location electronic resource

Access conditions

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

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