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. 2008 Mar-Apr;40(2):141-7.
doi: 10.1016/j.bcmd.2007.07.012. Epub 2007 Oct 29.

Significant increase of self-renewal in hematopoietic cells after forced expression of EVI1

Leopoldo Laricchia-Robbio  1 , Giuseppina Nucifora
Affiliations

Significant increase of self-renewal in hematopoietic cells after forced expression of EVI1

Leopoldo Laricchia-Robbio et al. Blood Cells Mol Dis. 2008 Mar-Apr.

Abstract

EVI1 was first identified as a preferential integration site of ecotropic retroviruses in the MDS1/EVI1 genomic locus leading to myeloid tumors in susceptible mice. Later studies showed that retroviral integration in the MDS1/EVI1 locus results in the emergence of a non-malignant dominant hematopoietic stem cell clone in non-susceptible mice strains, in non-human primates, and in patients, suggesting that a gene encoded by the locus could affect the self-renewal potential of a cell. The locus encodes two genes. One of them, EVI1, has long been associated with myeloid leukemia. To understand whether EVI1 has a role in self-renewal control, we forcibly expressed EVI1 in the bone marrow progenitors of two mice strains that differ in their proliferation and self-renewal potential. By comparing the response of the hematopoietic cells to EVI1, we conclude that EVI1 has a role in prolonging the self-renewal potential of the cells and that this ability of EVI1 is limited and modulated by inherent characteristics of the cells.

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Figures

Figure 1
Figure 1. Intrinsic strain-specific properties determine the potential for cell self-renewal in vitro
In vitro cultured Lin- C57BL/6J BM cells generate visible colonies in 3 consecutive platings (panel A). Progenitor cells obtained from DBA2 mice lose their clonogenicity earlier (panel B). Note that DBA2 cells consistently generate a higher number of colonies.
Figure 2
Figure 2. EVI1 enhancement of clonogenicity and colony formation is strain-independent
EVI1 equally affects the ability to form hematopoietic colonies when expressed in Lin- cells of two different mice strains. The ratio between the number of EVI1 colonies (red bars) and vector colonies (blue bars) for C57BL/6J cells (panel A) is approximately the same as for DBA2 cells (panel B).
Figure 3
Figure 3. In vitro EVI1 doubles the self-renewal potential of murine primary HSCs independently of the mouse strain
EVI1 (red bars) doubles the number of consecutive platings that generate visible colonies for C57BL/6J cells (panel A) and DBA2 cells (panel B).
Figure 4
Figure 4. Morphologic comparison of EVI1-positive C57BL/6J and DBA2 cells
In contrast to C57BL/6J control cells (upper left panel), the DBA2 control cells (lower left panel) show an advanced state of differentiation characterized by large cytoplasm and compact nuclei. The expression of EVI1 in C57BL/6J cells (upper right panel) and DBA2 (lower right panel) cells delays terminal differentiation in vitro.
See this image and copyright information in PMC

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