All cells undergo an important switch during their lifetime, changing from unspecialized cells undergoing rapid growth into specific cell types that perform the duties of specific tissues and organs, a process called differentiation. Researchers have begun to sort out the inner workings of the cell that lead to this important change.
Genes that Affect Cell Differentiation and Pluripotency
Pluripotency is the ability of a cell to differentiate into many different cell types.
Research from Na Xu, a postdoctoral fellow in Kenneth S. Kosik's lab at UC Santa Barbara, reported that the genes controlling the transformation from proliferation to specialization can be narrowed down to only a few genes. The research looked at microRNAs, small strands of RNA that act to lower the concentrations of transcription factors, proteins that bind to DNA, and turn genes on or off. These microRNAs block three specific genes and prevent the cell from differentiating into specific cell types.
Transcription Factors Work to Alter Cell Activity
Transcription factors control transcription, the production of messenger RNA from the DNA template. There are about 2,000 transcription factors in each cell, and the specific transcription factors active at a given time affect what stage the cell is in. Transcription factors don't work alone, however. They often form networks that affect each other's activity, making them difficult to study.
Researcher Timothy Ravasi at UC San Diego led a study, published online in Nature Genetics on April 19, 2009, using bioinformatic techniques to analyze all of the transcription activity taking place in a leukemia cell line over time and to identify which transcription factors were at work during different stages of cell development. Using this data, the researchers identified specific genes and transcription factors at work during different phases of cell development.
Controlling Differentiation Through Structural Changes
Another study published online March 2, 2009 in the Proceedings of the National Academy of Sciences looked at the protein complex BAF and how it controls the winding of DNA around the histone complex of chromosomes. As BAF alters the structure of the DNA helix, it controls transcription factors' access to those genes.
Another factor involved in the switch from rapidly dividing cells into specialized differentiated cells is the movement of ions across cell membranes. Tufts doctoral student Sarah Sundelacruz studied changes in voltage across the membranes of differentiating cells and discovered that changes in polarization can instruct cells to differentiate or to prevent differentiation.
The proximity of cells to each other and epigenetic factors that come from outside the cell may also have an effect on differentiation.
Why is Cell Differentiation Important?
Cell differentiation is a popular research topic among scientist because its implications affect many areas of biology.
In development, for example, all cells first undergo rapid growth before settling down into specialized jobs. Understanding this process could lead to potential stem cell therapies as well as helping prevent developmental problems in the womb. MicroRNAs in particular are viewed as a potential way to change differentiated adult cells back into pluripotent stem cells, which could then be used for therapeutic purposes, including wound healing and tissue regeneration.
Another area where cell differentiation is important is in cancer biology, where runaway growth causes disease. A thorough understanding of differentiation could lead to better cancer treatments.
Sources:
Ravasi ,T, et al. The FANTOM Consortium & Riken Omics Science Center. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell lineMay 2009, Nature Genetics Vol 41 No 5
Ho, Lena, et al. An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency. Proceedings of the National Academy of Sciences of the United States of America, 2009 Mar 31.
Na Xu, Thales Papagiannakopoulos, Guangjin Pan, James A. Thomson, and Kenneth S. Kosik. MicroRNA-145 Regulates OCT4, SOX2, and KLF4 and Represses Pluripotency in Human Embryonic Stem Cells. Cell, 2009
Sundelacruz S, Levin M, Kaplan DL. Membrane Potential Controls Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells. PLoS ONE, 2008
Bridget Coila - I'm a cell and molecular biologist, freelance writer and photographer currently living in Beijing, China. I'm fascinated by science, ...
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