Bmi‐1‐Green Fluorescent Protein‐Knock‐In Mice Reveal the Dynamic Regulation of Bmi‐1 Expression in Normal and Leukemic Hematopoietic Cells

Abstract

The ability to self-renew is essential for all kinds of stem cells regardless of tissue type. One of the best candidate genes involved in conferring self-renewal capacity is Bmi-1, which has been proven to be essential for the maintenance of both normal adult hematopoietic and leukemia stem cells, as well as adult neural stem cells. To investigate the possible role of Bmi-1 in other cell types that also self-renew, we generated Bmi-1-green fluorescent protein (

Cell intrinsic and extrinsic mechanisms of stem cell aging depend on telomere status

“…These data indicate that p16 might be one of the causal factors limiting stem cell function in aging wild type mice with long telomere reserves (Janzen et al, 2006;Krishnamurthy et al, 2006;Molofsky et al, 2006). In line with this hypothesis, expression of Bmi-1 (a repressor of p16) promotes stem cell self-renewal in wildtype mice (Hosen et al, 2007). In contrast to aging of wild type mice, p16 and p19ARF deletion did not improve organ maintenance and lifespan of telomere dysfunctional mice indicating that this pathway is not a major component limiting stem cell function in response to telomere dysfunction (Khoo et al, 2007) .…”

Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo

“…Interestingly, although BMI1 is not detectable in the immature differentiating neuronal layers, it appears to be strongly expressed again in the fully differentiated OMP + neuron layers. Several lines of evidence support this conclusion: we stained tissue from multiple animals, used antibodies recognizing different regions of BMI1 protein, and verified the expression pattern on tissue prepared from Bmi1 GFP+/− reporter mice, in which GFP was inserted as a knock-in to replace the coding region of Bmi1 (Hosen et al, 2007). Cre recombination in existing fully mature OMP + neurons is unlikely to explain neuronal β-galactosidase labeling in our inducible Bmi1 CreER fate mapping results, since we examined lesioned tissue in which the reporter-labeled neurons were newly generated during reconstitution of the epithelium after lesion, and OMP CreER+/− ;R26R lacZ mice were initially used for inducible fate mapping.…”

Establishment of a Normal Hematopoietic and Leukemia Stem Cell Hierarchy

“…We then investigated the relative expression levels of Bmi-1 within the hematopoietic cell hierarchy by generating green fluorescent protein (GFP) knockin mice expressed under endogenous transcriptional regulatory elements of the Bmi-1 gene. We found that Bmi-1 is expressed in HSCs at its highest levels and down-regulated upon commitment to differentiation (Hosen et al 2007). Looking at two murine leukemia models induced by p210BCR/ABL or TEL/PDGFβR + AML1/ETOm we found that expression of Bmi-1 was highest in leukemic HSCs compared to downstream progenitors, albeit at similar expression levels compared to normal HSCs (Hosen et al 2007).…”