The Prkci gene maintains the stem cells homeostasis in the adult body
One of the striking features of stem cells is their ability to make copies of themselves whenever it is required, a property known as 'self-renewal'. This process keeps cell division under control, which is required for continuous regeneration in the human body. It is very important to keep proliferation under check; otherwise, an excess of symmetric division can lead to teratoma formation, but also an insufficient number may inhibit the repair and maintenance of the body. In a nutshell, stem cells play a very crucial role in maintaining the homeostasis of the adult body.
Recently, scientists at University of Southern California in collaboration with University of California, San Diego, have found a key gene that maintains this critical balance of tissue homeostasis . They showed that an atypical PKC, Prkci, is a key player in regulating the switch from an expansion to a differentiation or maintenance phase through the Notch pathway.
They have shown through experiments that loss of Prkci can encourage stem cells to differentiate into the progenitor cells that form neurons, heart muscle, and blood. They differentiated Prkci knock-down mouse embryonic stem cells into embryo-like structures. Without Prkci, they favored self-renewal, generating large numbers of cells and, subsequently, an abundance of secondary structures. They also found those missing Prkci had many activated genes typical of stem cells, and some activated genes typical of neural, cardiac, and blood-forming cells.
The activation of Prkci is regulated by the Notch signaling pathway. In the absence of Prkci, the Notch pathway produces a protein that signals to stem cells to make more of themselves. In the presence of Prkci, the Notch pathway remains silent, and stem cells differentiate into specific cell types. Inhibition of Prkci activity with specific small-molecule inhibitors might be a powerful method to boost stem cell production in the context of injury or disease.
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- In Kyoung Mah, Rachel Soloff, Stephen M. Hedrick, Francesca V. Mariani. Atypical PKC-iota Controls Stem Cell Expansion via Regulation of the Notch Pathway. Stem Cell Reports, 2015 DOI:1016/j.stemcr.2015.09.021