Researchers from the University of Pennsylvania School of Medicine found that the activation of a molecular pathway important in stem cell and developmental biology leads to an increase in lung stem cells. Harnessing this knowledge could help develop therapies for lung-tissue repair after injury or disease. The investigators published their findings online last week in advance of print publication in Nature Genetics.
"The current findings show that increased activity of the Wnt pathway leads to expansion of a type of lung stem cell called bronchioalveolar stem cells," says senior author Edward Morrisey, Ph.D., Associate Professor of Medicine and Cell and Developmental Biology.
"This information will give us a more extensive basic understanding of Wnt signaling in adult tissue repair in the lung and other tissues and also start to help us determine whether pharmacological activation or inhibition of this pathway can be utilized for treatments," explains Morrisey, who is also the Scientific Director of the Penn Institute for Regenerative Medicine.
Activation of the Wnt signaling pathway leads to expansion, or increase in number, of bronchioalveolar stem cells in the lung. A protein called GATA6 inhibits Wnt signaling by directly regulating the expression of another protein in the Wnt pathway called frizzled 2 (Fzd2).
Wnt signaling is a major pathway in stem cell biology. The finding that GATA6 negatively regulates Wnt signaling and that GATA6 has been shown to play important roles in embryonic stem cell replication and differentiation suggests that these two pathways are linked not only in lung stem cells but in other tissues where they play important roles including the heart, gut, and pancreas.
"We were surprised by the robust activation of Wnt signaling after loss of GATA6 expression in the lung," says Morrisey. "Such a robust activation is rarely observed."
Wnt signaling can be pharmacologically modulated with compounds, including lithium, already approved by the FDA. Use of such compounds, both known and newly identified through ongoing screens, could allow for forced expansion and differentiation of key stem cell populations in the lung and other tissues for adult tissue repair after injury or disease.
Future directions of the Morrisey lab include not only a more extensive basic understanding of Wnt signaling in adult-tissue repair in the lung and other tissues, but also starting to determine whether pharmacological activation or inhibition of this pathway can really be utilized for treatments.
Source: University of Pennsylvania
Related stories:
Stem cells: forgotten by evolution?
Max Planck scientists show that adult stem cells are possibly just the remnants of evolution
For a fairly long time, adult stem cells have been a point of scientific interest. Besides the question of how to use them therapeutically, researchers have been investigating what exactly their physiological function could be. Not least because undifferentiated cells with features typical of stem cells are being increasingly found in organs like the liver, brain, and muscles, scientists are beginning to assume that these cells play a role in repairing organs.
A link between mitochondria and tumor formation in stem cells
Researchers report on a previously unknown relationship between stem cell potency and the metabolic rate of their mitochondria –a cell's energy makers. Stem cells with more active mitochondria also have a greater capacity to differentiate and are more likely to form tumors.
Healthy blood vessels may prevent fat growth
The cells lining blood vessels are known to be important for maintaining health, but researchers at the Indiana University School of Medicine believe these cells may perform an unsuspected task – controlling the development of fat cells. Their findings are reported in the September issue of the journal
Stem Cells.
Blood vessel cells are instructed to form tube-like structures
How do blood vessel cells understand that they should organise themselves in tubes and not in layers? A research group from Uppsala University shows for the first time that a special type of "instructor" molecule is needed to accomplish this. These findings, published in the scientific journal
Blood, might be an important step towards using stem cells to build new organs.
Limbs saved by menstrual blood stem cells
Cells obtained from menstrual blood, termed 'endometrial regenerative cells' (ERCs) are capable of restoring blood flow in an animal model of advanced peripheral artery disease. A study published today in BioMed Central's open access Journal of Translational Medicine demonstrates that when circulation-blocked mice were treated with ERC injections, circulation and functionality were restored.
Lack of Energy in Old Age Might Not Just Be Normal Part of Aging
"Old and tired" is such a common phrase, it’s no surprise that a new study in the Journal of Gerontology has found that almost 1 in 5 senior citizens report they have so little energy that they spend most of the day sitting on the sofa.
Recipe for cell reprogramming adds protein
A drug-like molecule called Wnt can be substituted for the cancer gene c-Myc, one of four genes added to adult cells to reprogram them to an embryonic-stem-cell-like state, according to Whitehead researchers. Researchers hope that such embryonic stem-cell-like cells, known as induced pluripotent (IPS) cells, eventually may treat diseases such as Parkinson's disease and diabetes.
Vitamin A pushes breast cancer to form blood vessel cells
Researchers at Georgetown University Medical Center have discovered that vitamin A, when applied to breast cancer cells, turns on genes that can push stem cells embedded in a tumor to morph into endothelial cells. These cells can then build blood vessels to link up to the body's blood supply, promoting further tumor growth.