Abstract/Details

Molecular mechanisms involved in commitment to the lymphoid lineage


2005 2005

Other formats: Order a copy

Abstract (summary)

We have found that common lymphocyte progenitors (CLP) in the mouse bone marrow maintain a latent myeloid developmental potential when stimulated through ectopic hIL-2Rβ receptors. Early thymocyte progenitors (ProT cells) also retain this latent myeloid developmental potential. Granulocyte/macrophage colonies arising from hIL-2Rβ transgenic ProT cells have initiated TCRβ gene rearrangement, a lymphoid specific event. The presence of TCRβ gene rearrangement illustrates that the ProT cells were truly diverted from the lymphoid to myeloid lineage induced by signaling through the ectopic cytokine receptor. The lymphoid to myeloid lineage switch is mediated through downregulation of the master B cell regulator Pax5 (BSAP). We show that Pax5 is downregulated by signaling through ectopic hIL-2Rβ as well as enforced expression of C/EBPα, two situations where lymphoid progenitors are diverted to the myeloid lineage. In addition, enforced expression of Pax5 in CLP blocks lineage conversion following IL-2 stimulation and restricts cells to the B cell lineage. These results indicate that hematopoietic cells are more plastic in their developmental potential than is currently thought.

Indexing (details)


Subject
Cellular biology
Classification
0379: Cellular biology
Identifier / keyword
Biological sciences; Hematopoiesis; Lymphoid; TCRbeta; Thymocyte progenitor cells
Title
Molecular mechanisms involved in commitment to the lymphoid lineage
Author
King, Angela Goffredo
Number of pages
134
Publication year
2005
Degree date
2005
School code
0212
Source
DAI-B 66/04, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
054208726X, 9780542087264
Advisor
Weissman, Irving L.
University/institution
Stanford University
University location
United States -- California
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3171818
ProQuest document ID
305434226
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305434226
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.