Review Articles in 2011

Cell-based therapy is a growing field that exploits advances in stem cell manipulation and gene transfer technologies. This Review discusses the latest developments and crucial challenges for this field, with an emphasis on haematopoietic stem cell gene therapy.

Converting somatic cells to induced pluripotent stem cells is becoming routine, but how much do we know about the mechanism of reprogramming? This Review discusses the epigenetic and transcriptional changes that occur and experimental strategies to probe this cell-fate switch.

Pluripotent stem cells can become any cell in the body, and yet achieving this in the laboratory is a challenge. Popular methods include directing differentiation using protein factors or small molecules, and an emerging alternative is reprogramming somatic cells directly from one fate to another.

Thanks to improved functional assays and more effective protocols for directed tissue differentiation, pluripotent stem cells are proving increasingly useful for uncovering the genetic and epigenetic basis of monogenic and complex diseases, and for investigating the functional consequences of genetic variation.

Structural variation in the genome can influence disease, complex traits and evolution, but comprehensive characterization of variants is challenging. This Review compares current methods — particularly microarray platforms and sequencing-based computational analysis — and considers future research strategies.

Methodological advances have provided new insights into mechanisms of enhancer function, including the importance of specific chromatin modifications at enhancers for the establishment of gene expression programmes. Cohesin and non-coding RNAs are also emerging as key players in enhancer function.

There are now myriad variations on techniques to reprogramme somatic cells into pluripotent stem cells, but which options should researchers choose? This Review sets out the choices, focusing on how the desired downstream application should guide the reprogramming strategy.

Advances in genetics, genomics and molecular biology are improving existing forensic approaches and providing new ones. The authors discuss improvements in DNA profiling, the growing field of forensic DNA phenotyping, and new molecular approaches that help to link sample donors to crimes.

Clefts of the lip and/or palate are common and have a complex genetic and environmental basis. Recent work on these birth defects illustrates the value of combining genome-wide association studies, animal models and improved clinical phenotyping. Future work may also address gene–environment interactions.

The reigning paradigm in population genetic theory has been that pleiotropy is pervasive, with every gene affecting every trait. Empirical data is now challenging this model, pointing towards a much more structured and restricted pleiotropy in which mutations affect only subsets of characters.

Molecular biology and sociobiology have operated largely as independent disciplines. But, as discussed in this Review, sociobiology theory can contribute greatly to our understanding of molecular systems by showing that networks are shaped by cooperative and competitive phenotypes across multiple levels of biological organization.

Sex chromosomes have raised many intriguing evolutionary questions, such as how these dynamic chromosomes arise and why their content differs from autosomes. Recently, empirical evidence has built on theoretical work and comparisons of XY and ZW systems are set to provide further insight.

The relative contribution of mRNA degradation and translational repression to gene regulation by plant and animal microRNAs has been controversial. This question, along with the molecular details of the two modes of regulation, has been addressed by several recent studies.

Forest trees have long generation times and large genomes, but they present unique research opportunities for understanding environmental adaptation and the basis of complex traits. Genomic resources are developing rapidly for many tree species, and the results are being translated to tree breeding and natural population management.

MicroRNAs and long non-coding RNAs regulate diverse aspects of animal embryogenesis. Recent evidence from several species shows their importance in driving and maintaining cell fate decisions, from early patterning through to tissue specification and morphogenesis.

How are specific genomic regions targeted for transcriptional silencing and how is stable silencing maintained? The Polycomb and heterochromatin silencing systems have distinct roles and yet share some interesting features, such as the involvement of non-coding RNAs, histone modifications and dynamic protein complexes.