Elsevier

Blood Cells, Molecules, and Diseases

Volume 39, Issue 3, November–December 2007, Pages 287-291
Blood Cells, Molecules, and Diseases

Insights into c-Myb functions through investigating colonic crypts

https://doi.org/10.1016/j.bcmd.2007.05.010Get rights and content

Abstract

c-Myb has been investigated in the context of the hematopoietic system where it has been shown to regulate progenitor cell expansion and differentiation of a number of lineages. The capacity to grow and expand specific blood cell lineages in vitro using well defined growth factors plus the vast range of cell surface lineage markers that identify different cell types has driven our understanding of the spectrum of roles that c-Myb plays in this tissue compartment. In addition, c-Myb is also an important transcription factor in non-hematopoietic tissues but the restricted spectrum of cell phenotyping reagents has hampered in-depth investigation. In the case of the colonic crypt the absence of phenotyping reagents of the quality employed in identifying blood cell lineages is partly compensated for by the spatial and temporal information that is inherent in the crypt structure. Using different tools to those used in the blood system we have gained insights in the multiple roles played by c-Myb in colon epithelial cells. These observations, when combined with the understanding of c-Myb action in blood cells, is providing a clearer view as to how c-Myb operates in normal cells and how this is subverted in diseases like cancer.

Section snippets

c-Myb in hematopoiesis

c-Myb seems to participate in almost every part of the hematopoietic system and as best exemplified by c-myb null embryos that show defects in all lineages [1], [2], [3]. The action of c-Myb begins with stem cells, uncommitted progenitor cells and finally differentiated cells of the myeloid, lymphoid, erythroid and megakaryocytic pathways (see Reviews [1], [3]). Numerous in vitro studies of fetal liver cells, bone marrow-derived cells and peripheral blood cells combined with mutant mouse

The utility of studying colonic crypt cells

Contrasting the strengths and difficulties associated with the blood system are the opportunities provided by the structural consistency and functional information of the colonic crypt. These units in mouse may have 500 or more cells that are hierarchically ordered and are remarkably uniform from one adult mouse to another. They turn over every 3–7 days and during the lifetime of a mouse produce and discard an enormous number of cells. Importantly, they produce three distinct cell lineages

The role of c-Myb in colon biology

When considering the role of c-Myb in colon biology it is appropriate to describe it in three contexts. One is the role during organogenesis and development, the second where crypts are fully formed having achieved a homeostatic state and the third is under conditions of cytotoxic stress such as that generated by radiation or cytotoxic damage. In the first case fetal colon transplant studies showed that gut tissue from c-myb null embryos failed to form colonic epithelia with crypt structures in

Acknowledgments

The National Health and Medical Research Council and Cancer Council of Victoria supported this work and RGR is a recipient of an NHMRC Research Fellowship from this organization. Thanks to Dr. Maree Overall for manuscript preparation. This paper is based on a presentation at a Focused Workshop of the 4th Myb Workshop on “Myb2007” sponsored by The Leukemia & Lymphoma Society in Civitella Alfedena, Italy, May 20th–24th 2007.

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