Journal Club: Stem Cell Biology, Reproductive Biology, Prions, Allergy & Immunology

Graduate Division

STEM CELL BIOLOGY: Two miRNA clusters reveal alternative paths in late-stage reprogramming. Parchem, R.J., et al. (Blelloch). Cell Stem Cell. 2014 Mar 11. Epub ahead of print.

The ability to effectively convert fully differentiated cells into stem cells through the addition of a few specific factors has produced an explosion of research and a Nobel Prize. It remains unclear, however, the degree to which this rewinding to a stem cell needs to proceed through all intervening developmental stages.

The microRNA families mir-290 and mir-302, each of which can repress hundreds of genes at once, have been shown to promote pluripotency. The Blelloch lab used reporters of these clusters to study dedifferentiation.

The researchers found that during normal differentiation, mir-290 is expressed before mir-302. Treatment with the stem-cell inducing regimen OSK, however, frequently led to expression of either only mir-290 or mir-302. Addition of Sall4 to the induction protocol increased the frequency of mir-302 followed by mir-290 expression and increased the efficiency of induced pluripotent stem cell production.

REPRODUCTIVE BIOLOGY: Use of a mouse in vitro fertilization model to understand the developmental origins of health and disease hypothesis. Feuer, S.K. et al. (Rinaudo). Endocrinology. 2014 Mar 31. Epub ahead of print.

The use of assisted reproductive technologies such as in vitro fertilization (IVF) has allowed many people to overcome infertility during the past few decades. Although IVF generally results in babies of good health, there has been some evidence of increased risks of metabolic and cardiovascular problems, such as high blood pressure, as they age.

In this study, Feuer and colleagues used mouse IVF to study how early deviations from the typical in utero environment have long-term effects on the health of the mice.

They found that even using the IVF protocol considered optimal, IVF-derived mice have impaired glucose tolerance and altered fat deposition. They showed increased expression of the metabolic regulator TXNIP in IVF blastocysts and continued dysregulation of this gene into adulthood. The authors argue for the importance of follow-up in IVF-conceived humans to determine the degree to which similar problems are present.

PRIONS: Evidence that bank vole PrP is a universal acceptor for prions. Watts, J.C. PLoS Pathog. 2014. 10(4):e1003990.

Prions are infectious proteins that self-propagate their aberrant conformation, resulting  in fatal neurogenerative diseases such as Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, often called mad cow disease.

The specific protein responsible, PrP, differs slightly between different mammals. It is often not transmissible across species barriers, though the exact process for this resistance remains incompletely understood. In contrast to mice, bank voles are susceptible to prions from many species, such as humans.

In this paper, the authors created a transgenic mouse expressing the bank vole PrP. They observed that these mice, like bank voles, were much more susceptible to prions from many mammals. They suggest the bank vole PrP is a universal acceptor and propose future research to determine how it is so sensitive. 

ALLERGY & IMMUNOLOGY: Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and γδ T cells. Van Dyken, S.J. et al. (Locksley). Immunity. 2014. 40(3):414-24.

Chitin is an extremely abundant polysaccharide found in, among other places, the shells of arthropods and the cell walls of fungi. It is thought to be important in allergies to dust mites and mold.

Although the downstream immune response to chitin has been well characterized, the set of signals leading from chitin reaching the lung to this inflammatory response was not so clear.

Here, members of the Locksley lab showed that three inflammatory signaling molecules produced by lung epithelium in response to chitin were non-redundant in activating innate type 2 lymphoid cells (ILC2s), which in turn were essential for eosinophil and alternatively activated macrophage responses. In contrast, targeted deletion of ILC2s resulted in increased inflammatory activity by γδ T cells.