Review about retroviral-induced leukemogenesis and the CSC hypothesis

Hematopoietic stem cells and retroviral infection by Prabal Banerjee, Lindsey Crawford, Elizabeth Samuelson and Gerold Feuer, Retrovirology 2010(Feb 4); 7(1): 8 [Epub ahead of print][Connotea bookmark][[FriendFeed entry][PubMed Citation][Full text (PDF)].

Includes sections on Leukemia Stem Cells/Cancer Stem Cells (LSC/CSC) and on The Cancer Stem Cell Hypothesis.

Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic SC

Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells by E Camilla Forsberg and 6 co-authors, including Irving L Weissman, PLoS One 2010(Jan 20);5(1):e8785. [Connotea bookmark][FriendFeed entry][Full text is publicly accessible (via Libre OA)]. PubMed Abstract:

Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells.

Understanding of bone marrow SC niche expanded

Detection of functional haematopoietic stem cell niche using real-time imaging by Yucai Xie, Tong Yin, Winfried Wiegraebe and 15 co-authors, including Ricardo A Feldman and Linheng Li, Nature 2008(Dec 3) [Epub ahead of print]. PubMed Abstract:

Haematopoietic stem cell (HSC) niches, although proposed decades ago, have only recently been identified as separate osteoblastic and vascular microenvironments. Their interrelationships and interactions with HSCs in vivo remain largely unknown. Here we report the use of a newly developed ex vivo real-time imaging technology and immunoassaying to trace the homing of purified green-fluorescent-protein-expressing (GFP(+)) HSCs. We found that transplanted HSCs tended to home to the endosteum (an inner bone surface) in irradiated mice, but were randomly distributed and unstable in non-irradiated mice. Moreover, GFP(+) HSCs were more frequently detected in the trabecular bone area compared with compact bone area, and this was validated by live imaging bioluminescence driven by the stem-cell-leukaemia (Scl) promoter-enhancer. HSCs home to bone marrow through the vascular system. We found that the endosteum is well vascularized and that vasculature is frequently localized near N-cadherin(+) pre-osteoblastic cells, a known niche component. By monitoring individual HSC behaviour using real-time imaging, we found that a portion of the homed HSCs underwent active division in the irradiated mice, coinciding with their expansion as measured by flow assay. Thus, in contrast to central marrow, the endosteum formed a special zone, which normally maintains HSCs but promotes their expansion in response to bone marrow damage.

Found via: Understanding Of Bone Marrow Stem Cell Niche Expanded, individualall.net Health News. Excerpt:

“EVISC technology will allow us to study HSC lineage commitment in vivo,” said Linheng Li, Ph.D., Investigator and senior author on the paper. “Furthermore, we will be able to use this technology to study leukemia (and other cancer) stem cells to better understand whether they use the same or different niches that normal stem cells use, and even to evaluate drug resistance and treatment responses. This is an exciting new avenue for our work.”