The protein TAZ sends 'mixed signals' to stem cells

Just as beauty exists in the eye of the beholder, a signal depends upon the interpretation of the receiver. According to new USC research published in Stem Cell Reports, a protein called TAZ can convey very different signals -- depending upon not only which variety of stem cell, but also which part of the stem cell receives it. When it comes to varieties, some stem cells are "naïve" blank slates; others are "primed" to differentiate into certain types of more specialized cells. Among the truly naïve are mouse embryonic stem cells (ESCs), while the primed variety includes the slightly more differentiated mouse epiblast stem cells (EpiSCs) as well as so-called human "ESCs" -- which may not be true ESCs at all. In the new study, PhD student Xingliang Zhou and colleagues in the laboratory of Qi-Long Ying demonstrated that naïve mouse ESCs don't require TAZ in order to self-renew and produce more stem cells. However, they do need TAZ in order to diff...
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Colon of patients with IBS reacts differently to bacteria

Salmonella bacterium interacting with microvilli in human colon.
Credit: Maria Vicario, Universitat Autonoma de Barcelona
The intestinal barrier of patients with the gastrointestinal disease IBS allows bacteria to pass more freely than in healthy people, according to a study led by researchers at Linköping University in Sweden. The study, published in the scientific journal Gastroenterology, is the first to investigate IBS using living bacteria.
IBS, or irritable bowel syndrome, disturbs bowel function. The condition leads to repeated episodes of abdominal pain, and usually gives rise to constipation or diarrhea. Around 10% of people in Sweden suffer from IBS, and it is twice as common among women as among men.
"People affected by IBS have been regarded as a rather diffuse group. Our study has shown that people with IBS are clearly different from healthy people in the way in which the part of the intestine known as the colon (or large intestine) reacts to bacteria," says Åsa Keita, researcher at the Department of Clinical and Experimental Medicine (IKE). She has led the study together with Susanna Walter, specialist in gastrointestinal diseases at Linköping University Hospital and also a researcher at IKE.
It is still unclear why the condition arises, but there is increasing evidence that changes in the way in which the brain interacts with the bacterial flora in the gut play a role. The large intestine has a layer of mucous, which constitutes the first line of defence against the bacteria in the intestine. Behind this, there is a layer of epithelial cells known as enterocytes, and behind these is tissue that contains immune cells. The present study has looked at this layer of epithelial cells, and examined how permeable it is to bacteria.
The researchers investigated small samples of tissue taken from the large intestine of 37 women with IBS, and compared them with samples from women with no intestinal symptoms. They studied the membranes in an instrument known as a Ussing chamber, in which it is possible to measure the transport of substances and bacteria through living tissue.
Infection with the pathogenic bacterium Salmonella typhimurium is a risk factor for developing IBS, and this led the researchers to investigate how this Salmonella strain interacts with the intestinal membrane. They also studied a strain of E. coli (Escherichia coli HS), which is usually present in the intestine. Both bacteria passed through the intestinal mucosa of patients with IBS around twice as rapidly as was the case for healthy subjects.
"Patients with IBS in our study had a higher passage of bacteria in the model system. But we cannot transfer this result directly to clinical practice, and further research is needed. What we can say, however, is that there is something that makes one layer of the intestinal mucosa of patients with IBS more sensitive to bacteria than in healthy subjects," says Åsa Keita.
The researchers also looked at mast cells, a type of immune cell that is an important component of the innate immune defence, which protects against micro-organisms. They found that mast cells appear to play a significant role in regulating the passage of bacteria across the intestinal membrane, in both healthy subjects and in people with IBS. The mechanism seems, however, to be more active in those with IBS.



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