Aptly named visceral endoderm

The very early mouse embryo is initially covered by a layer of cells called visceral endoderm that despite its name (visceral means associated with internal organs) was only thought to give rise to extraembryonic structures. Now, in this issue of Developmental Cell, Kwon et al. (2008) show unexpectedly that a significant population of visceral endoderm cells does contribute, along with epiblast-derived endoderm, to the embryo proper.     

Cortex shatters the glass ceiling

Recreating developmental structures in vitro has been a primary challenge for stem cell biologists. Recent studies in Cell Stem Cell (Eiraku et al., 2008) and Nature (Gaspard et al., 2008) demonstrate that embryonic stem cells can recapitulate early cortical development, enabling them to generate specific cortical subtypes.     

Rehabilitation of a contract killer: caspase-3 directs stem cell differentiation

Activation of caspase-3 is generally acknowledged as a penultimate step in apoptotic cell death pathways. Two studies in this issue of Cell Stem Cell (Fujita et al., 2008; Janzen et al., 2008) provide compelling data to demonstrate that caspase-3 is also a conserved inductive cue for stem cell differentiation.     

Swapping nucleotides, tuning Hsp70

Molecular chaperones such as heat shock protein 70 (Hsp70) are crucial for protein folding. Crystal structures of Hsp70 in a complex with the nucleotide exchange factor (NEF) Hsp110 reported in this issue of Cell (Polier et al., 2008) and in Molecular Cell (Schuermann et al., 2008) provide new insights into how NEF action specifies Hsp70 cellular function.     

IFITM1-mediated cell repulsion controls the initial steps of germ cell migration in the mouse

In this issue of Developmental Cell, a novel mechanism for the initiation of germ cell migration in the mouse has been identified, based upon differential expression of interferon-inducible transmembrane proteins in the gastrula (Tanaka et al., 2005). Germ cells are displaced by a repulsion mechanism from the posterior mesoderm into the endoderm.     

Unexpected pieces to the senescence puzzle

Although initially described as the end state of cells after extended rounds of division in culture, it is now clear that cellular senescence induced by different stimuli plays an important role in tumor suppression in vivo. Three recent studies in Cell report that secreted proteins play an important role in enforcing the senescence response (Acosta et al., 2008; Kuilman et al., 2008; Wajapeyee et al., 2008). These new studies identify unanticipated contributors to this tumor-suppressing cell state.     

Autophagy: a sweet process in diabetes

Autophagy is inhibited by the insulin-amino acid-mTOR signaling pathway. Two papers in this issue of Cell Metabolism (Ebato et al., 2008; Jung et al., 2008) provide evidence that basal autophagy is necessary to maintain the architecture and function of pancreatic beta cells and that its induction in diabetic mice protects beta cells against damage by oxidative stress.     

Converting human skin cells to neurons: a new tool to study and treat brain disorders?

Recent publications in Cell Stem Cell (Son et?al., 2011; Ambasudhan et?al., 2011), PNAS (Pfisterer et?al., 2011), and Nature (Caiazzo et?al., 2011; Pang et?al., 2011; Yoo et?al., 2011) report that functional neurons can be directly generated from human fibroblast cells without going through the pluripotent state.     

A ubiquitin-like protein unleashes ubiquitin ligases

Modification of cullin-RING ubiquitin ligases by the ubiquitin-like molecule Nedd8 promotes substrate ubiquitination. A crystal structure of a cullin modified by Nedd8 recently reported in Cell (Duda et al., 2008) and a biochemical study in Molecular Cell (Saha and Deshaies, 2008) reveal the dramatic impact on the ligase machinery by conjugation of ubiquitin or ubiquitin-like proteins.     

The origins of blood: induction of hematopoietic stem cells from different sources

Ex vivo hematopoiesis from embryonic sources offers exciting promises in basic research and medicine. In this issue of Cell Stem Cell, Ledran et al. (2008) describe human embryonic stem cell (hESC)-derived hematopoiesis, while Taoudi et al. (2008) define the origin of definitive hematopoietic stem cells (HSCs) from the mouse aorta-gonad-mesonephros (AGM) region.     

Using notches to track mammary epithelial cell homeostasis

Notch signals mediate a wide range of activities in development and cancer. A report in this issue of Cell Stem Cell (Bouras et al., 2008) demonstrates that Notch serves as a switch that controls cell fate and tissue homeostasis in mammary epithelium.     

Manipulating midbrain stem cell self-renewal

In this issue of Cell Stem Cell, Falk and colleagues (Falk et al., 2008) demonstrate that differential responsiveness to TGF-beta signaling selectively modulates self-renewal of dorsal midbrain stem cells. This observation may lead to strategies for expanding specific neural stem cell subtypes.     

Transcriptional ShortCUTs

Recent work from Kuehner and Brow (2008) and Thiebaut et al. (2008) in Molecular Cell and Jenks et al. (2008) in Molecular and Cellular Biology reveals that regulated expression of central nucleotide synthesis pathway components directs start site-dependent RNA polymerase II termination.     

Genetic modification-free reprogramming to induced pluripotent cells: fantasy or reality?

Significant development in the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has been achieved by retroviral infection of defined genes. Several recent reports, including one in this issue of Cell Stem Cell (Marson et al., 2008), have started to replace these genetic changes with specific chemical stimulation.     

Uncapping the potential of renal stem cells

In this issue of Cell Stem Cell, McMahon and coworkers (Kobayashi et al., 2008) characterize a subset of progenitor cells in the developing kidney. six2-expressing mesenchymal cells exhibit hallmark stem cell traits, in that they appear to self-renew and are clonally multipotent for a range of nephron epithelial cell types.     

Fly-let biology and the high protein/low carb diet

In Drosophila, a simple network of nutrient-sensing neuroendocrine cells, analogs of pancreatic islet alpha and beta cells, regulates carbohydrate metabolism. Work presented in this issue of Cell Metabolism (Buch et al., 2008) shows that signals from these cells control expression of a glycogen-specific glucosidase in response to dietary protein and carbohydrate.     

Stem cell regulation and host defense: the logic and the paradox

Stem cell-based cardiac regeneration requires a detailed understanding of the factors that induce cardiac lineage commitment. In this issue of Cell Stem Cell, Lindsley et al. (2008) and Bondue et al. (2008) use embryonic stem cells to identify a key role for Mesp1 in this process.     

T-Box genes and developmental decisions that cells make

During gastrulation in vertebrate embryos, three definitive germ layers (ectoderm, mesoderm, and endoderm) are formed by organized and coordinated cell movements. In zebrafish, further subdivision of the mesoderm gives rise to the axial, adaxial and paraxial mesoderm. The axial mesoderm contributes to the prechordal plate and notochord whereas the adaxial and paraxial cells give rise to slow and fast muscles, respectively (Devoto et al., 1996; Blagden et al., 1997; Currie and Ingham, 1998). An inductive interaction in which the notochord plays an essential role will also provide an input in forming other specialized types of tissue contributing to the axial structures: the floor plate located dorsally to the notochord in the ventral spinal cord and the hypochord located ventrally of the notochord and deriving probably from the endoerm. It is known that despite the difference in developmental roles (Str?hle et al., 1993; Krauss et al., 1993), the floor plate and hypochord co-express a number of common molecular markers (Jan et al., 1995; our unpublished results) that may illustrate a certain similarity of their origin. Their close proximity to the notochord determines specialized features of these structures that differ substantially from the rest of the neural tube and endoderm, correspondingly. Once formed under the influence of the notochordal signaling, the floor plate will acquire an ability, similar to the notochord, to express genes of the Hedgehog family and several other groups of genes and to induce specification of ventral cell types in the neural tube during later development (for review, see Korzh, 1998). The biology of the hypochord is much less understood. It seems that the hypochord develops slightly later than the floor plate. It may be required for proper positioning of the dorsal aorta as well as induction of some other endoderm derivatives.