Are Hematopoietic Stem Cells Generated in the Placenta?

In this issue of Cell Stem Cell, the origin of multipotent hematopoietic cells present in the placenta has been assessed in Ncx1(-/-) embryos lacking a functional heart and circulation. Rhodes and colleagues (Rhodes et al., 2008) found lymphoid progenitors in the placenta, as well as in dorsal aorta and yolk sac and vitelline vessels, indicating that they arose in situ.     

The Missing Niche for Spermatogonial Stem Cells: Do Blood Vessels Point the Way?

Although spermatogonial stem cell niches have been defined in lower organisms, their definitive localization in mammalian seminiferous tubules has been elusive. In a recent Science paper, Yoshida et al. (2007) elegantly demonstrated a vascular and interstitial tissue-associated niche for undifferentiated spermatogonia in the mouse.     

Hematopoietic Stem Cells in Neonates: Any Differences between Very Preterm and Term Neonates?

Background

In the last decades, human full-term cord blood was extensively investigated as a potential source of hematopoietic stem and progenitor cells (HSPCs). Despite the growing interest of regenerative therapies in preterm neonates, only little is known about the biological function of HSPCs from early preterm neonates under different perinatal conditions. Therefore, we investigated the concentration, the clonogenic capacity and the influence of obstetric/perinatal complications and maternal history on HSPC subsets in preterm and term cord blood.

Methods

CD34+ HSPC subsets in UCB of 30 preterm and 30 term infants were evaluated by flow cytometry. Clonogenic assays suitable for detection of the proliferative potential of HSPCs were conducted. Furthermore, we analyzed the clonogenic potential of isolated HSPCs according to the stem cell marker CD133 and aldehyde dehydrogenase (ALDH) activity.

Results

Preterm cord blood contained a significantly higher concentration of circulating CD34+ HSPCs, especially primitive progenitors, than term cord blood. The clonogenic capacity of HSPCs was enhanced in preterm cord blood. Using univariate analysis, the number and clonogenic potential of circulating UCB HSPCs was influenced by gestational age, birth weight and maternal age. Multivariate analysis showed that main factors that significantly influenced the HSPC count were maternal age, gestational age and white blood cell count. Further, only gestational age significantly influenced the clonogenic potential of UCB HSPCs. Finally, isolated CD34+/CD133+, CD34+/CD133– and ALDH^high HSPC obtained from preterm cord blood showed a significantly higher clonogenic potential compared to term cord blood.

Conclusion

We demonstrate that preterm cord blood exhibits a higher HSPC concentration and increased clonogenic capacity compared to term neonates. These data may imply an emerging use of HSPCs in autologous stem cell therapy in preterm neonates.     

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.     

Where's the ecology in molecular ecology?

Molecular techniques have had a profound impact in biology. Major disciplines, including evolutionary biology, now consistently utilize molecular tools. In contrast, molecular techniques have had a more limited impact in ecology. This discrepancy is surprising. Here, we describe the unexpected paucity of ecological research in the field colloquially referred to as 'molecular ecology.' Publications over the past 15 years from the journals Ecology , Evolution and Molecular Ecology reveal that much of the research published under the molecular ecology banner is in fact evolutionary in nature, and that comparatively little ecological research incorporates molecular tools. This failure to more broadly utilize molecular techniques in ecology is alarming because several promising lines of ecological inquiry could benefit from molecular approaches. Here we summarize the use of molecular tools in ecology and evolution, and suggest several ways to renew the ecological focus in 'molecular ecology'.     

Where's the evidence?

Science is in large part the art of careful measurement, and a fixed measurement scale is the sine qua non of this art. It is obvious to us that measurement devices lacking fixed units and constancy of scale across applications are problematic, yet we seem oddly laissez faire in our approach to measurement of one critically important quantity: statistical evidence. Here I reconsider problems with reliance on p values or maximum LOD scores as measures of evidence, from a measure-theoretic perspective. I argue that the lack of an absolute scale for evidence measurement is every bit as problematic for modern biological research as was lack of an absolute thermal scale in pre-thermodynamic physics. Indeed, the difficulty of establishing properly calibrated evidence measures is strikingly similar to the problem 19th century physicists faced in deriving an absolute scale for the measurement of temperature. I propose that the formal relationship between the two problems might enable us to apply the mathematical foundations of thermodynamics to establish an absolute scale for the measurement of evidence, in statistical applications and possibly other areas of mathematical modeling as well. Here I begin to sketch out what such an endeavor might look like.     

What is the purpose of launching World Journal of Stem Cells?

The first issue of World Journal of Stem Cells (WJSC), whose preparatory work was initiated on September 27, 2008, will be published on December 31, 2009. The WJSC Editorial Board has now been established and consists of 281 distinguished experts from 28 countries. Our purpose of launching WJSC is to publish peer-reviewed, high-quality articles via an open-access online publishing model, thereby acting as a platform for communication between peers and the wider public, and maximizing the benefits to editorial board members, authors and readers.     

β1 Integrin Maintains Integrity of the Embryonic Neocortical Stem Cell Niche

During embryogenesis, the neural stem cells (NSC) of the developing cerebral cortex are located in the ventricular zone (VZ) lining the cerebral ventricles. They exhibit apical and basal processes that contact the ventricular surface and the pial basement membrane, respectively. This unique architecture is important for VZ physical integrity and fate determination of NSC daughter cells. In addition, the shorter apical process is critical for interkinetic nuclear migration (INM), which enables VZ cell mitoses at the ventricular surface. Despite their importance, the mechanisms required for NSC adhesion to the ventricle are poorly understood. We have shown previously that one class of candidate adhesion molecules, laminins, are present in the ventricular region and that their integrin receptors are expressed by NSC. However, prior studies only demonstrate a role for their interaction in the attachment of the basal process to the overlying pial basement membrane. Here we use antibody-blocking and genetic experiments to reveal an additional and novel requirement for laminin/integrin interactions in apical process adhesion and NSC regulation. Transient abrogation of integrin binding and signalling using blocking antibodies to specifically target the ventricular region in utero results in abnormal INM and alterations in the orientation of NSC divisions. We found that these defects were also observed in laminin α2 deficient mice. More detailed analyses using a multidisciplinary approach to analyse stem cell behaviour by expression of fluorescent transgenes and multiphoton time-lapse imaging revealed that the transient embryonic disruption of laminin/integrin signalling at the VZ surface resulted in apical process detachment from the ventricular surface, dystrophic radial glia fibers, and substantial layering defects in the postnatal neocortex. Collectively, these data reveal novel roles for the laminin/integrin interaction in anchoring embryonic NSCs to the ventricular surface and maintaining the physical integrity of the neocortical niche, with even transient perturbations resulting in long-lasting cortical defects.