Development: Leveraging Bank Deposits

Pamela J. Hines

Stem cells are essential, yet exceedingly scarce, components of regenerating tissues such as skin and blood. The more broadly useful stem cell—the pluripotent stem cell—can be derived from embryo cells. Remarkably, cells with similar potential can be derived from more specialized cells that have been induced to backtrack under the direction of a suite of four transcription factors. Nevertheless, each of these stem cell sources suffers from distinct problems of availability, utility, and ethics.

Two groups introduce another source of pluripotent stem cells: umbilical cord blood. This blood can be collected fairly easily with little risk to the donor, has suffered less exposure than adult cells to environmental insult, and has found favor in recent years as a source of hematopoietic stem cells. Giorgetti et al. show that pluripotency can be induced, even from previously frozen cord blood bank samples, with the use of only two transcription factors. Haase et al. describe the derivation of pluripotent cells from the endothelial cells of cord blood and demonstrate the differentiation of these into cells similar to cardiomyocytes (shown above with a cardiac-specific isoform of the muscle protein troponin T in red).

Cell Stem Cell 5, 353; 434 (2009).

Immunology: Sensing Non-Self DNA

Kristen L. Mueller

One way the immune system recognizes infection is by sensing the presence of foreign nucleic acids in the cytoplasm. Although it had been established that microbial double-stranded DNA (dsDNA) triggered the production of the inflammatory cytokine interferon-β, the identity of the dsDNA sensor remained elusive.

Chiu et al. and Ablasser et al. suggest that RNA polymerase III (Pol III) is the culprit. Pol III, which transcribes genes encoding several kinds of RNA (such as transfer and ribosomal), has been shown to be present in the cytoplasm, but what it did there was unclear. These authors show that cytoplasmic Pol III transcribes AT-rich microbial dsDNA into 5'-triphosphate–containing RNA that is then detected by the retinoic acid–induced gene I (RIG-I), which proceeds to switch on the production of interferon-β. In the absence of Pol III, infection with Legionella pneumophila or Epstein-Barr virus does not induce interferon-β, indicating that Pol III is required for proper immunity both to bacterial and to viral infection.

Cell 138, 576 (2009); Nat. Immunol. 10, 1065 (2009).

Evolution: Something from Nothing

Guy Riddihough

Gene duplication is a common means for generating the raw material of new genes, especially because the duplicated coding and regulatory regions provide a ready-made, fully active substrate for evolutionary processes that lead to sub- or neofunctionalization. The de novo origin of genes—which refers to the so-called orphan genes whose ancestry cannot be traced to known genes—is less frequently encountered and thought to occur when transposable elements or genome rearrangements bring together fragments of genetic clay from which a transcribable structure can be built.

Heinen et al. identify an orphan gene that has been born directly from a virgin intergenic region in the mouse genome. This gene is limited to the genus Mus and appeared roughly 3 million years ago. It is under positive selection, having been subject to a selective sweep in the recent past. Although there are two open reading frames in the transcript, it seems to function as a noncoding RNA that is alternatively spliced and hence named Polymorphic derived intron-containing (Poldi). Poldi is expressed in mouse testis, and knockout of the gene results in reduced testis weight and sperm motility. As differential expression of Poldi requires only a simple promoter, and cryptic splicing and polyadenylation signals are already present in intergenic regions, the birth of new genes may be less rare than we thought.

Curr. Biol. 19, 1527 (2009).