Research Highlights in 2013

In a recent paper published in Cell Research, Yan Bao and colleagues characterize a new population of IFNγ-producing innate-like B cells that promotes innate immune responses and contributes to early pathogen control following intracellular bacterial infection.

A major challenge in regenerative medicine is the generation of functionally effective target cells to replace or repair damaged tissues. Transdifferentiation in vivo is a novel strategy to achieve cell fate conversion within the native physiological niche; this technology may provide a time- and cost-effective alternative for applications in regenerative medicine and may also minimize the concerns associated with in vitro culture and cell transplantation.

How the novel influenza H7N9 virus crossed species barrier from avian to human is intriguing. Extrapolation from previous studies on H5N1 can be misleading as illustrated by crystallographic studies on the H7 hemagglutinin with G226L substitution; crystal structure of the neuraminidase N9 showed that R294K substitution interferes with binding to sialic acid or antiviral drugs and reduces viral fitness.

In a recent paper in Nature, Ermolaeva et al. uncover a systemic response to DNA damage in germ cells that protects somatic tissues, providing mechanistic insight into the bidirectional communication between germ line and soma.

Antibiotic therapies disrupt the intestinal microbiota and render the host susceptible to enteric infections. A recent report by Ng et al. explores the ability of two intestinal pathogens (Salmonella enterica serovar Typhimurium and Clostridium difficile) to use this disruption to their advantage and consume host carbohydrates that would otherwise be unavailable in the presence of a normal gut microbiota.

Several studies have demonstrated the clonal transmission of distinct differentiation and self-renewal properties in hematopoietic stem cells during the regeneration of blood production in transplanted recipients. A recent publication now identifies Vwf expression as a discriminating marker of a hematopoietic stem cell state that is primed for platelet production in response to thrombopoietin, but also subject to developmental and other, as yet undefined, cues.

Trisomy 21 in human causes Down syndrome, a common chromosome disorder with devastating phenotypes ranging from early death in utero to intellectual disability together with an array of physical anomalies and late-onset diseases. In a recent study published in Nature, Jeanne Lawrence and her colleagues restored normal gene expression in trisomy 21 cells by silencing the extra chromosome using XIST, the non-coding RNA that normally silences one X chromosome in females; this improved growth and differentiation of neural cells, which offers hope that some deleterious effects of the trisomy could be reversed to improve this incurable disease.

Since its discovery in 1989, researchers strive after a small animal model for Hepatitis C virus infection, so far with very limited success. A study recently published in Nature now for the first time reports the recapitulation of the complete life cycle of this virus in inbred mice with a functional adaptive immune system.

In the September issue of Cell Research, Wan et al. analyze the Chinese Alligator genome and identify multiple instances of positively-selected changes in protein-coding genes and expansions of multi-gene families that appear to explain suites of phenotypes central to the unique habits and physiology of crocodilian reptiles. They demonstrate the effectiveness of comparative systems genomics in integrating information from comparative genomics, molecular evolution, and systems biology to understand the evolutionary dynamics of complex systems.

FOR20, a conserved centrosomal protein, is essential for Plk1 to localize to the centrosome during the S phase and regulate DNA replication. The absence of either Plk1 or FOR20 can stall the cell cycle by a previously unknown intra-S phase centrosomal checkpoint.

Acetylcholine is a cellular mediator selected early in evolution as a key neurotransmitter, but its other biological roles including immune-modulation remain to be elucidated. In a recent paper published in Cell Research, Sun et al. report that acetylcholine modulates cytokine production in macrophages via microRNA-124.

Intestinal bacterial metabolites are an important communication tool between the host immune system and the commensal microbiota to establish mutualism. In a recent paper published in Science, Wendy Garrett and her colleagues report an exciting role of the three most abundant microbial-derived short-chain fatty acids (SCFA), acetic acid, propionic acid and butyric acid, in colonic regulatory T cell (cTreg) homeostasis.

In a recent paper published in Cell, He and colleagues reported the identification and functional characterization of Beclin 2, a mammal-specific homolog of the evolutionarily conserved autophagy-regulatory and oncosuppressive factor Beclin 1. In spite of a non-negligible degree of sequence identity, Beclin 1 and Beclin 2 differ from each other in multiple aspects, including their functional profile as well as the genomic organization of the respective loci.

It has been a long-standing enigma which scramblase causes phosphatidylserine residues to be exposed on the surface of apoptotic cells, thereby facilitating the phagocytic recognition, engulfment and destruction of apoptotic corpses. In a recent paper in Science, Nagata and coworkers reveal that the scramblases Xkr8 and its C. elegans ortholog, CED-8, are activated by caspase cleavage in apoptotic cells.

There exists a worldwide shortage of donor livers for transplant. This may not pose a problem in the future, as Takebe et al. have recently grown functional “liver buds” from stem cells in a dish.

Pluripotency can be experimentally induced from somatic cells by nuclear transfer, fusion with embryonic stem cells, or ectopic transcription factor induction, but attempts to recapitulate this process by chemical means alone have previously failed. In a recent paper published in Science, Hou et al. pursue a rational, albeit laborious approach to identify cocktails of small molecules whose treatment restores pluripotency in adult somatic cells.

The fact that mammals are diploid sets a barrier to rapidly understand the function of non-coding and coding genes in the genome. Recently, Yang et al. reported successful derivation of monkey haploid embryonic stem cells from parthenotes, which provide an effective platform for studying mammalian gene function and enable reverse genetic screening of genes for recessive phenotypes in monkeys.

Fine scale genomic regulation is critical for maintaining genomic integrity and is often disrupted in neurodevelopmental disorders. An intriguing new study reveals the intricate biochemical complexity of de novo post-translational modifications of MeCP2, including activity-dependent protein-protein interactions that 'bridge' the nuclear receptor co-repressor (NCoR) complex to chromatin and lead to alterations in gene expression that characterize Rett syndrome.

A novel coronavirus, the Middle East respiratory syndrome coronavirus, recently emerged through zoonotic transmission, causing a severe lower respiratory tract infection in humans. In two recent papers, one published in Cell Research, the crystal structure of the viral receptor-binding domain in complex with the host CD26/dipeptidyl peptidase 4 receptor has now been characterized.

The tumor-suppressive activity of PTEN has always been attributed to its endogenous intracellular function. Recently two different groups have demonstrated that PTEN is secreted/exported into the extracellular environment for uptake by recipient cells, and functions as a tumor suppressor in a cell non-autonomous manner.