Yaks That Adapt to Low Oxygen Environments

There has been recent insight into adaptations, genetically and cellularly, that allow yaks to survive in high altitude environments. It has been determined that this ability to live in these kinds of environments could be a result of endothelial lung cells specific to yaks. The endothelial lung cells are a single layer lined with blood vessels that regulates the exchanges between the bloodstream and surrounding tissues. High altitude regions in the Tibetan Plateau are inhabited by both domestic and wild yaks. They experience low oxygen concentrations. Humans and other non-native mammals would experience extreme heart and lung issues if exposed to such low oxygen conditions. This is not the case for the yaks who have adapted to these conditions over millions of years.  

A group of scientists explored just how yaks are adapted to these kinds of environments by combining transcriptomic and genomic data to present an exclusive genome assembly for both domestic and wild yaks. Transcriptomic data involves characterizing all transcription activity (both coding and non-coding) or a select subset of RNA transcripts within the sample. This analysis allows for the identification of candidate genes and expressed markers of traits of interest associated. This also included a map of the different lung cell types present. 127 genes were identified to be expressed differently in yaks compared to European cattle and identified a subtype of endothelial cells only found in the lung tissue of yaks. This specific cell type was shown to express genes involved in high altitude adaptation. These findings on genetic adaptations of yaks and high-altitude environments can be useful for future studies on how other mammals respond to low oxygen environments.  

Using Fibroblasts to Create New Blood Vessels

        Cardiovascular researchers at Houston Methodist have learned that they can use fibroblast cells and convert them into endothelial cells which will create blood vessels. Fibroblasts are the cells that cause scar tissue and are abundant in the human body. John Cooke, the study's main researcher, says that this is the first time that small molecules and proteins have been converted into a therapeutic cell type.  Cook's hope for this discovery is that it will be used to improve the healing of cardiovascular injuries and other injuries throughout the body that require an increase in circulation.There have already been studies done that use viruses to transform cells into those need in the body, but there are limitations and many risks that go along with this form of transformation. It is believed that using small molecules and proteins will be more safe for use.

The top picture shows fibroblasts stained blue, and the bottom picture shows the amount of fibroblasts that transformed into endothelial cells after treatment with poly I:C and VEGF

         The new method and Cook and his other researchers proposed involves exposing the fibroblasts to poly I:C (polyinosinic:polycytidylic acid) that will cause the cells to think that they are being attacked by a virus. Poly I:C is a small segment of RNA that binds to the host cell receptor TLR3. This viral attack caused the fibroblast cells to reorganize their nuclear chromatin, which allowed genes that had previously been blocked off to be expressed. Factors, such as VEGF, were the applied to the fibroblasts because these factors are known to cause certain cells to convert into endothelial cells. This treatment caused 2% of all the fibroblasts in the body to be transformed into endothelial cells, the same percentage outcome as using a virus to transform the cells. Cooke claims that he has unpublished work that shows that up to 15% of the fibroblasts can be converted using his method.
       
         In order to prove the effectiveness of the new cells, Cooke injected the cells into mice that had the need for new blood vessels in their hind limbs for circulation. Once the cells were introduced to the mice, the blood vessel number increased in the hind limbs and blood flow was improved. Cooke believes that his findings will pave the way for more studies to continue and possibly lead to finding ways to regenerate mass amounts of damaged tissue in humans.

       This is a very interesting study that goes to show that there are many different ways to manipulate the cells of the human body, and as our knowledge of genetics continues to grow, many more interesting findings like this will occur.

Original Article: Reprogrammed cells grow into new blood vessels

New Blood Vessels from Reprogrammed Fibroblasts

Scar cells(top) transformed into blood vessels. The
proof of transformation is indicated by the red color in
the bottom picture. The red is an indicator for CD31,
a protein made by blood vessels. 

Cardiovascular scientists from Houston Methodist, Stanford University, and Cincinnati Children’s Hospital teamed up in a joint effort to study fibroblasts, cells that cause scarring. Our bodies are filled with an immense amount of fibroblast. Through their study, the scientists discovered that the fibroblasts can be transformed into endothelium, a cell type that forms the lining of blood vessels. The method first involves polyinosinic:polycytidylic acid (poly I:C), a segment of double-stranded RNA, being introduced to fibroblasts. Poly I:C binds to TLR3(toll-like receptor 3), which fools the fibroblast cell into believing it was attacked by a virus. This resulted in a rearrangement of nuclear chromatin, which allowed genes to be expressed that were once restricted. After rearrangement, the fibroblast was treated with VEGF, Vascular endothelial growth factor, which allowed the fibroblasts to become endothelial cells.

"To our knowledge, this is the first time that trans-differentiation to a therapeutic cell type has been accomplished with a small molecules and proteins," explained chairperson, John Cooke, M.D. Houston Methodist Research Institute Department of Cardiovascular Sciences.

The next step in their research involved taking the transformed fibroblasts and introducing them to immune-deficient mice. The immune-deficient mice had poor blood circulation, however, with the transformed fibroblasts the number of vessels in the limbs of the mice increased, and ultimately improving circulation.

"The cells spontaneously form new blood vessels -- they self assemble," Cooke said. "Our transformed cells appear to form capillaries in vivo that join with the existing vessels in the animal, as we saw mouse red blood cells inside the vessels composed of human cells."

Although procedures like this have been performed, this is the first time a small molecule has been reprogrammed.  Research groups were able to generate endothelial cells from infectious viruses, viruses that were programmed to manipulate DNA cells. However, this process involves a more complicated approach. Viruses also have the potential to damage patient’s chromosomes. The small-molecule transformation of cells is a safer approach that will be utilized in clinical trials. The new research also helps our society take one step further into regenerative medicine. The new discovery will definitely help humans who suffer from poor blood circulation and cardiovascular health affects, by improving their condition through the formation of new blood vessels.

Article: http://www.sciencedaily.com/releases/2014/11/141107131658.htm

Article Related: Fibroblasts - http://ghr.nlm.nih.gov/glossary=fibroblast