Cell & Developmental Biology
Primary cilia are hair-like structures which protrude from almost all mammalian cells. They are thought to be sensory and involved in sampling the cell’s environment. New research, published in BioMed Central’s open access journal Cilia, launched April 27, shows that cilia on cells in the retina and liver are able to make stable connections with each other — indicating that cilia not only are able to sense their environment but are also involved in cell communication.
Primary cilia are structurally and functionally very similar to eukaryotic flagella (motile tails used to propel microorganisms). For many decades it was thought that cilia on human cells were primarily for movement, for example, cilia on respiratory cells drive mucous up and out of the airways by beating together, however it is now believed that they are also ‘cellular antennae’ — important for cell to cell communication.
In order to find out how these cilia could physically communicate Carolyn Ott and Jennifer Lippincott-Schwartz, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, examined primary cilia from the retina, bile duct and in cultured cells. In all cases, cilia between nearby cells formed long-lasting contacts with each other, something that has never been observed before. The adhesions between cilia lasted hours or days and were dependent on interactions between glyco proteins (proteins with a sugar molecule attached).
Jennifer Lippincott-Schwartz explained, “A number of human genetic diseases, including Bardet-Biedl syndrome, nephronophthisis, Joubert, and Meckel-Gruber syndrome, are due to defects in ciliary trafficking and signaling. Our study suggests that cilia are active transmitters and seek out neighboring cells to communicate with. These newly discovered cilia-cilia contacts may be disrupted in ciliopathies, an intriguing possibility that requires further investigation.”
The findings are published in Cilia, a new Open Access journal from BioMed Central. Cilia is a peer-reviewed journal that publishes high quality basic and translational research on the biology of cilia and diseases associated with ciliary dysfunction. Research approaches include cell and developmental biology, use of model organisms, and human and molecular genetics.
Cell & Developmental Biology
Researchers at NYU Langone Medical Center have discovered a protein called TAT-5 that affects the production of extracellular vesicles, small sacs of membrane released from the surface of cells, capable of sending signals to other cells. When released extracellular vesicles can affect tumor spread, blood clotting and inflammation. Their discovery gives new insight into how extracellular vesicles form, and reveals new potential strategies to manipulate diseases such as cancer.
“Very little is known about how cells release extracellular vesicles from their surfaces, so the discovery of TAT-5 opens the door to learning how to manipulate their numbers and thus affect cell communication,” said Jeremy Nance, PhD, associate professor of Cell Biology at NYU School of Medicine and a member of the Developmental Genetics Program at the Skirball Institute of Biomolecular Medicine.
Researchers at NYU Langone studied the embryo of the worm C. elegans and discovered that TAT-5 inhibits the budding of extracellular vesicles from the surface of cells. Several types of tumors produce extracellular vesicles that can induce tumor cell invasion or metastasis. Researchers found they can use tat-5 mutants as a tool to study how extracellular vesicles are formed, enabling the design of strategies to regulate their formation. In the study, researchers also discovered that two proteins that regulate viral budding are involved in extracellular vesicle release, suggesting that budding of viruses and release of extracellular vesicles might occur through similar mechanisms, and that this research may reveal new strategies to inhibit viral spread.
Cell & Developmental Biology
The lining of the intestine regenerates itself every few days as compared to say red blood cells that turn over every four months. The cells that help to absorb food and liquid that humans consume are constantly being produced. The various cell types that do this come from stem cells that reside deep in the inner recesses of the accordion-like folds of the intestines, called villi and crypts.
But exactly where the most important stem cell type is located — and how to identify it — has been something of a mystery. In fact, two types of intestinal stem cells have been proposed to exist but the relationship between them has been unclear. One type of stem cell divides slowly and resides at the sides of intestinal crypts. The other divides much more quickly and resides at the bottom of the crypts.
Some researchers have been proponents of one type of stem cell or the other as the “true” intestinal stem cell. Recent work published this week in Science from the lab of Jonathan Epstein, MD, chairman of the Department of Cell and Developmental Biology from the Perelman School of Medicine at the University of Pennsylvania, may reconcile this controversy. The findings suggest that these two types of stem cells are related. In fact, each can produce the other, which surprised the researchers.
“We actually began our studies by looking at stem cells in the heart and other organs,” Epstein said. “In other tissues in the body, slowly dividing cells can sometimes give rise to more rapidly dividing stem cells that are called to action when tissue regeneration is required. Our finding that this can happen in reverse in the intestine was not expected.”
The discovery that rapidly cycling gut stem cells can regenerate the quiescent stem cells — slowly dividing and probably long-lived — suggests that the developmental pathways in human organs that regenerate quickly like in the gut, skin, blood, and bone, may be more flexible than previously appreciated.
“This better appreciation and understanding may help us learn how to promote the regeneration of tissue-specific adult stem cells that could subsequently help with tissue regeneration,” says Epstein. “It may also help us to understand the cell types that give rise to cancer in the colon and stomach.”
Stem cell (blue) from the intestinal crypt.