HUNTSVILLE, Ala – Tales from the crypt are supposed to be scary, but new research from Vanderbilt University, the HudsonAlpha Institute for Biotechnology, and colleagues shows that crypts can be places of renewal too: intestinal crypts, that is. Intestinal crypts are small areas of the intestine where new cells are formed to continuously renew the digestive tract. By focusing on one protein expressed in our intestines called Lrig1, the researchers have identified a special population of intestinal stem cells that respond to damage and help to prevent cancer.
The research, published in the March 30 issue of Cell, also shows the diversity of stem cells in the intestines is greater than previously thought.
“Identification of these cells and the role they likely play in response to injury or damage will help advance discoveries in cancer,” said Shawn Levy, Ph.D., faculty investigator at the HudsonAlpha Institute and an author on the study.
The intestines and colon are normally lined with a single layer of cells to absorb nutrients from food. There are regular small pockets in the intestines called crypts, where stem cells are gathered. Rapid turnover of the lining cells and replacement by new lining cells made in the crypt, keep the intestines and colon healthy and keep damaged cells from turning into cancerous ones.
The new paper demonstrates that, although the makeup of stem cells in the crypt is still controversial, one protein called Lrig1 can distinguish a group of long-lived cells at the base of the crypt. These Lrig1-positive stem cells do not regularly replace lining cells, but instead are only activated when there is damage or injury to the intestine.
In addition, the researchers show that the Lrig1 protein functions to prevent cancer as a tumor suppressor molecule. When the protein is completely absent from a mouse model, the mice all develop adenomas and then tumors. This suggests that Lrig1 is an important target for understanding and treating intestinal and colon cancer.
Levy added, “RNA sequencing work at HudsonAlpha found that the Lrig1-positive stem cells are molecularly different in multiple ways from previously identified crypt stem cells, in keeping with their role in responding to damage.” Further work on genes expressed or silenced in this population of cells, he added, will increase understanding of both normal and cancer cell progression in the intestines.
The paper, “The Pan-ErbB Negative Regulator Lrig1 Is an Intestinal Stem Cell Marker that Functions as a Tumor Suppressor” was published in the March issue of Cell.
Media Contact: Beth Pugh
About HudsonAlpha: HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to innovating in the field of genomic technology and sciences across a spectrum of biological problems. Its mission is three-fold: sparking scientific discoveries that can impact human health and well-being; fostering biotech entrepreneurship; and encouraging the creation of a genomics-literate workforce and society. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. Designed to be a hothouse of biotech economic development, HudsonAlpha’s state-of-the-art facilities co-locate scientific researchers with entrepreneurs and educators. The relationships formed on the HudsonAlpha campus allow serendipity to yield results in medicine and agriculture. Since opening in 2008, HudsonAlpha, under the leadership of Dr. Richard M. Myers, a key collaborator on the Human Genome Project, has built a name for itself in genetics and genomics research and biotech education, and boasts 26 biotech companies on campus.