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.     

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.     

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.     

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.     

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.     

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.     

LIS1 and spindle orientation in neuroepithelial cells

Asymmetric stem cell division is thought to require precise orientation of the mitotic spindle. However, a recent study in Cell (Yingling et al., 2008) analyzes the role of LIS1 in the developing mouse brain and shows that spindle orientation is more important during early, symmetric progenitor cell divisions than for later asymmetric divisions.     

Cancer: Inappropriate Expression of Stem Cell Programs?

Cancer stem cells (CSCs) are a subpopulation of cancer cells that possess characteristics, including self-renewal, associated with normal stem cells. In this issue of Cell Stem Cell, Wong et al. (2008) define a core embryonic stem cell (ESC)-like gene expression program that may be important for CSC function in multiple epithelial cancers.     

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.     

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.     

Small RNAs loom large during reprogramming

In two independent Cell Stem Cell reports, the Morrisey and Mori groups show that human and mouse somatic cells can be reprogrammed to produce induced pluripotent stem cells by expressing microRNAs, completely eliminating the need for ectopic protein expression (Anokye-Danso et al., 2011; Miyoshi et al., 2011).     

Tracing the life of the kidney tubule- re-establishing dogma and redirecting the options

Renal pathology suggests that tubular repair results from tubular proliferation. In contrast, recent studies propose that postnatal kidney repair may involve renal stem cells. In this issue of Cell Stem Cell, Humphreys et al. (2008) use lineage tracing to genetically assess contribution of adult nontubular cells (potentially stem cells) to repair of damaged renal tubules.     

Human ES Cells and a Blastocyst from One Embryo: Exciting Science but Conflicting Ethics?

In this issue of Cell Stem Cell, Chung et al. (2008) remove a single blastomere to generate a human embryonic stem cell (hESC) line without prejudicing the development of the biopsied embryo. Their method stimulates new ideas about hESC formation, but ethicopolitical concerns remain.