Adult stem cells precisely control their maintenance and differentiation by interacting with the microenvironment. However, little is known about how signals from the microenvironment are dynamically and differentially transmitted and function in stem cells and their differentiated daughter cells, which in turn leads to asymmetric division of stem cells.
Chen Dahua's laboratory and Tao Yi's laboratory of the Institute of Zoology, Chinese Academy of Sciences used Drosophila reproductive stem cells as research objects to carry out meaningful discussions on this basic scientific issue in developmental biology and made important progress. They found that the differentiation-promoting protein Fused is highly expressed in differentiated daughter cells (CB) and lowly expressed in stem cells (GSC). Further analysis found that the expression of Fused depends on the strength of the BMP signaling pathway in the microenvironment. The mutual antagonistic effect of BMP receptor Tkv and Fused produces a steep BMP concentration gradient, which determines the different fate of stem cells and their differentiated cells to renew themselves and differentiate.
Interestingly, the authors found that the BMP activity gradient and Fused-mediated antagonistic BMP activity gradient have formed in pre-CB in differentiated precursor cells in a bistable form, thus dynamically controlling the expression level of the main differentiation gene bam in Convert between CB. The study of molecular system dynamics further reveals the bistable structure of the feedback regulation mechanism that determines the fate of GSC. Evidence from molecular biology clearly shows that the formation of bistable structures during stem cell differentiation is mainly dependent on the strength of exogenous BMP signals.
These results are of great significance for understanding the physical mechanism of microenvironmental signals controlling the asymmetric division of stem cells and the response gradient of endogenous BMP, and can predict the behavior of stem cells. The bistable model of asymmetric division of Drosophila reproductive stem cells may be extended to most stem cell systems (including mammalian adult stem cells), and has guiding significance for future research in related fields.
BMP concentration gradient produced by the antagonistic action of BMP receptor Tkv and Fused
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