Understanding hematopoietic stem cells : from macro to micro
Abstract/Contents
- Abstract
- Recent technological advances in high throughput technology, sample preparation and data analysis have made whole genome mRNA and miRNA analysis of purified hematopoietic cell populations much more accessible. The high throughput analysis of the hematopoietic stem cell (HSC) population has yielded massive amounts of data and now we are in the process of biologically validating these targets. Esam1 is one target yielded from microarray analysis of the HSC population. We found Esam1 to be highly and selectively expressed by HSC from mouse bone marrow. Esam1 is also a viable positive HSC marker in fetal, young and aged mice, as well as in mice of several different strains. In addition, we find robust levels of Esam1 transcripts in purified human HSC. Esam1-/- mice do not exhibit severe hematopoietic defects, however, Esam1-/- BM has an increased frequency of HSC and fewer T cells. HSC from Esam1-/- mice give rise to more granulocyte/monocytes in culture and a higher T cell:B cell ratio upon transplantation into congenic mice. These studies identify Esam1 as a novel, widely applicable HSC-selective marker and suggest that Esam1 may play roles in both HSC proliferation and lineage decisions. MicroRNA-125b (miR-125b) is a target yielded from miRNA profiling of the HSC population. We show that miR-125b is highly expressed in HSC and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1lo CD34- lymphoid balanced and the Slamf1negCD34- lymphoid biased cell subsets within the multipotent HSC [CD34-KLS] fraction. This enrichment of HSC subsets occur via an anti-apoptotic mechanism, reducing the mRNA expression levels of two pro-apoptotic targets, Bmf and KLF13. The anti-apoptotic effect of miR-125b is more pronounced in the lymphoid biased HSC subset because of their intrinsic higher baseline levels of apoptosis. Together, these data reveal that miR-125b regulates hematopoietic stem cell survival and can promote lymphoid fate decisions at the level of the HSC by preferentially expanding lymphoid balanced and lymphoid biased 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 | Ooi, Ann Gee Lisa | |
|---|---|---|
| Associated with | Stanford University, Department of Chemical and Systems Biology. | |
| Primary advisor | Weissman, Irving L | |
| Thesis advisor | Weissman, Irving L | |
| Thesis advisor | Beachy, Philip Arden | |
| Thesis advisor | Mitchell, Beverly Eileen | |
| Thesis advisor | Rando, Thomas A | |
| Thesis advisor | Wysocka, Joanna, Ph. D | |
| Advisor | Beachy, Philip Arden | |
| Advisor | Mitchell, Beverly Eileen | |
| Advisor | Rando, Thomas A | |
| Advisor | Wysocka, Joanna, Ph. D |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Ann Gee Lisa Ooi. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Ann Gee Lisa Ooi
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...