Tissue injury in marrow transdifferentiation.

Recent findings indicate that adult BM contains cells that can differentiate into mature, nonhematopoietic cells of multiple tissues including cells of the kidney, lung, liver, skin and GI tract and fibers of heart and skeletal muscle. Recently the number of these observations has substantially increased, but there is a lack of information on the mechanistic issues in stem cell plasticity. In three different models for skin, liver and skeletal muscle plasticity, we have shown that following transplantation of the marrow cells from green fluorescent protein (GFP) transgenic mice, high levels of conversion of marrow cells can be identified. Injury to the tissue was the single most important factor for this phenomenon since the incidence of marrow to other tissue conversions significantly increased after tissue injury was implemented. Our studies also demonstrate the effect of radiation on the extent of marrow conversion.

Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice.

SNF5/INI1 is a component of the ATP-dependent chromatin remodeling enzyme family SWI/SNF. Germ line mutations of INI1 have been identified in children with brain and renal rhabdoid tumors, indicating that INI1 is a tumor suppressor. Here we report that disruption of Ini1 expression in mice results in early embryonic lethality. Ini1-null embryos die between 3.5 and 5.5 days postcoitum, and Ini1-null blastocysts fail to hatch, form the trophectoderm, or expand the inner cell mass when cultured in vitro. Furthermore, we report that approximately 15% of Ini1-heterozygous mice present with tumors, mostly undifferentiated or poorly differentiated sarcomas. Tumor formation is associated with a loss of heterozygocity at the Ini1 locus, characterizing Ini1 as a tumor suppressor in mice. Thus, Ini1 is essential for embryo viability and for repression of oncogenesis in the adult organism.