Stem cell division is regulated by the microRNA pathway

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Abstract
The trademark property of stem cells is their capacity to multiply in tissues when other cells are quiescent. Somehow they by-pass the cell division stop signals. An experiment in which microRNA processing was blocked in Drosophila germline stem cells suggests that these gene-silencing regulatory molecules are part of a mechanism that makes stem cells insensitive to environmental signals that normally stop cells at the G1/S transition in the cell cycle. Without microRNAs, germ cells stop dividing just like ‘normal’ cells. Three papers in last week's Nature highlighted the role of microRNAs in human cancer: it is possible that the unregulated division of tumour cells and the regulation of stem cell division are two sides of the same microRNA coin. On the cover, stem cells lacking microRNAs stop dividing due to over-production of the tumour suppressor p21/p27. One of the key characteristics of stem cells is their capacity to divide for long periods of time in an environment where most of the cells are quiescent. Therefore, a critical question in stem cell biology is how stem cells escape cell division stop signals. Here, we report the necessity of the microRNA (miRNA) pathway1,2,3,4 for proper control of germline stem cell (GSC) division in Drosophila melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded RNaseIII essential for miRNA biogenesis, revealed a marked reduction in the rate of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but are defective in cell cycle control. On the basis of cell cycle markers and genetic interactions, we conclude that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint. Hence, the miRNA pathway might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle at the G1/S transition.