Controlling intracellular traffic in stem cells can determine its fate
24 Feb 2018
By Dr. Deepa Subramanyam, Intermediate Fellow
A double-off switch for controlling traffic in stem cells
Recently published work from our lab revealed that intracellular trafficking machinery in stem cells can bring about changes in cell fate.
Understanding how different cells are formed is a fascinating question. Even more intriguing is the fact that the information to form all these diverse cell types is present in the single-celled zygote, formed by the fertilization of the egg by the sperm. The zygote undergoes a series of divisions over next 3 days, to form a structure called the blastocyst. Cells located within the blastocyst give rise to the entire organism. These cells can also be isolated and maintained in culture, and are called embryonic stem cells (ESCs). Similar to the cells within the embryo, ESCs also possess the capability to generate all the cell types present in the body. So what makes an ESC so special?
It has been shown that the process of vesicular trafficking, endocytosis, which is the transport of molecules using membrane-bound organelles, can affect the state of a stem cell. We attempted to identify whether specific trafficking pathways were functional in stem cells compared to differentiated cells, and whether this could play a role in maintaining the stemness of ESCs. In other words does an ESC have a specific pattern of expression of genes involved in endocytosis, and does this change when an ESC forms a specialized cell?
In our recently published study, we analyzed the expression of endocytosis associated genes (EAGs) in ESCs versus differentiated cells. Our analysis revealed that the expression of specific EAGs was repressed specifically in ESCs compared to differentiated cells by a novel mechanism involving the action of two modes of repression – transcriptional and post-transciptional. Transcriptional repression involved the action of the Polycomb complex, and post-transcriptional repression involved the action of small non-coding RNAs called microRNAs. Misexpression of these genes in ESCs resulted in a shift out of the stem cell state and towards a differentiated state.
Our results suggest that changing the expression of EAGs, and perhaps the functioning of the intracellular trafficking machinery in stem cells, can bring about changes in cell fate.
Dual repression of endocytic players by ESCC microRNAs and the Polycomb complex regulates mouse embryonic stem cell pluripotency. Ridim D. Mote, Gaurang Mahajan, Anup Padmanabhan, Ramaraju Ambati and Deepa Subramanyam. Scientific Reports. December 2017.
Banner image credit: Dr M. Zernicka-Goetz, Gurdon Institute. Wellcome Images. Description: Three-dimensional reconstruction of an early mouse embryo at the blastocyst stage. A blastocyst is formed around three to four days in the mouse and around five or six days after fertilization in humans.