Breaking the cell cycle of HSCs by p57 and friends

The cell cycle regulators involved in maintaining the quiescence, and thereby the self-renewal capacity, of somatic stem cells have long been elusive. Two new Cell Stem Cell articles in this issue (Matsumoto et?al., 2011; Zou et?al., 2011) now show that the CDK inhibitor p57 is a crucial brake for cycling HSCs, and links self-renewal activity to cell cycle quiescence.     

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.     

Moving right along: how PP1 helps clear the checkpoint

Spindle checkpoint silencing is crucial for cell-cycle progression, but mechanisms underlying this process remain mysterious. Two papers, one in this issue of Developmental Cell (Meadows et?al., 2011) and one in Current Biology (Rosenberg et?al., 2011), begin to show how phosphatase PP1-gamma connects chromosome-microtubule attachment with anaphase entry.     

The powerstroke and camshaft of the RIG-I antiviral RNA detection machine

The innate immune sensor RIG-I responds to infection by binding to viral double-stranded RNA (dsRNA). In this issue of Cell, Kowalinski et?al. (2011) and Luo et?al. (2011) reveal the structure of RIG-I, and in combination with functional analyses, they show how RIG-I recognizes viral RNA to initiate signaling and a type I interferon response.     

Wnt to notch relay signaling induces definitive hematopoiesis

The molecular mechanisms specifying hematopoietic stem cells (HSCs) in the vertebrate embryo remain poorly understood. Recently in Nature, Traver and colleagues demonstrate that timed wnt to Notch relay signaling across multiple cell types serves as an early upstream mechanism of HSC induction in zebrafish (Clements et?al., 2011).     

Does N-Cadherin Regulate Interaction of Hematopoietic Stem Cells with Their Niches?

In this issue of Cell Stem Cell, Kiel et al. (2007) demonstrate that N-cadherin is not expressed on repopulating hematopoietic stem cells (HSCs) and that reduction of osteoblasts does not affect HSC frequency, suggesting that other molecular pathways may also modulate the interaction of HSCs with their niches.     

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.     

Oxidative-reductionist approaches to stem and progenitor cell function

In this issue of Cell Stem Cell, Daquinag et?al. (2011) take a lesson from the oncology field to search for stromal progenitor cells within adipose tissue. Their use of phage display biopanning in?vivo identified an isoform of the extracellular matrix protein decorin as a receptor for the adipokine resistin.     

An epigenetic Tet a Tet with pluripotency

DNA and chromatin-modifying enzymes establish an ESC/iPSC-specific epigenomic landscape that is linked to a network of pluripotency genes and influences differentiation potential. In this issue of Cell Stem Cell, Koh?et?al. (2011) highlight Tet1 and Tet2 as key players in this network of coordinated genetic and epigenetic control.     

Pluripotency without Max

Myc/Max complexes are thought to be essential for maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). In this issue of Cell Stem Cell, Hishida et?al. (2011) provide genetic evidence that this requirement can be bypassed in well-defined culture conditions.     

Not so lonely at the top for cancer stem cells

A subpopulation of cancer cells is believed to be responsible for tumor initiation, propagation, and metastasis. In this issue of Cell Stem Cell, Dieter et?al. (2011) show that these functions in colon cancer can be ascribed to distinct tumor-initiating cell populations.     

When BMP meets FGF

Bone morphogenic proteins (BMPs) act as inducers of diverse cellular fates in human embryonic stem cells, but the mechanisms responsible remain poorly understood. In this issue of Cell Stem Cell, Bernardo et?al. (2011) demonstrate that different BMP-induced differentiation programs may be orchestrated by similar key target genes.     

Myotonic Muscular Dystrophy,RNA Toxicity,and the Brain: Trouble Making the Connection?

The study of rare genetic diseases is complicated by the inaccessibility of relevant cells and tissues, especially for neurologic disorders. In this issue of Cell Stem Cell, Marteyn et?al. (2011) use human embryonic stem cells to identify deficits in neuritic outgrowth in myotonic dystrophy type 1.     

Wnt signaling in the niche

There is much interest in understanding the signals in the bone marrow niche that keep hematopoietic stem cells (HSCs) in a quiescent state. In the current issue of Cell Stem Cell, Fleming et al. (2008) report that blocking Wnt signaling in the niche increases the number of proliferating HSCs and reduces their ability to reconstitute the hematopoietic system of irradiated recipient mice. These findings show that Wnt/beta-catenin activity is crucial for the maintenance of HSC quiescence in the bone marrow niche.     

A web of imprinting in stem cells

Imprinted genes are the prototypical epigenetically regulated genes. On the basis of findings in adult lung stem cells, Zacharek et?al. (2011) suggest in this issue of Cell Stem Cell that epigenetic silencing of imprinted genes is a common requirement for maintaining self-renewal in adult stem cell populations.     

What your heart doth know

Combining embryological insight with careful analysis of early stage cardiomyocyte differentiation, Kattman et?al. (2011) in this issue of Cell Stem Cell have defined minimal culture conditions to efficiently produce cardiomyocytes from hESCs and hiPSCs. The lessons learned are applicable to the derivation of other organotypic cell types.     

A new twist on clock protein phosphorylation: a conformational change leads to protein degradation

Progressive phosphorylation of circadian clock proteins is a hallmark of time-keeping. In this issue of Molecular Cell, Querfurth et?al. (2011) demonstrate that phosphorylation of Neurospora FRQ induces?a conformational change, which can account for its temporally gated degradation.     

Committing to a hairy fate: epigenetic regulation of hair follicle stem cells

Chromatin modifications are important for embryonic stem cell (ESC) pluripotency, but their functions in adult stem cells are less clear. In this issue of Cell Stem Cell, Lien et?al. (2011) delineate histone methylation patterns in hair follicle stem cells and show that these marks differ from those of ESCs.     

Haploid embryonic stem cells and the dominance of recessive traits

Diploidy, though essential for normal development, is a foil to geneticists. Two recent studies (Elling et?al., 2011, this issue of Cell Stem Cell; Leeb and Wutz, 2011, Nature), report the isolation of haploid pluripotent mouse ESCs, thus enabling efficient functional screening for genes involved in diverse cellular and developmental processes.