Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation.

Maternal embryonic leucine zipper kinase (MELK) was previously identified in a screen for genes enriched in neural progenitors. Here, we demonstrate expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for self-renewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice. Overexpression of MELK enhances (whereas knockdown diminishes) the ability to generate neurospheres from MNPs, indicating a function in self-renewal. MELK down-regulation disrupts the production of neurogenic MNP from glial fibrillary acidic protein (GFAP)-positive progenitors in vitro. MELK expression in MNP is cell cycle regulated and inhibition of MELK expression down-regulates the expression of B-myb, which is shown to also mediate MNP proliferation. These findings indicate that MELK is necessary for proliferation of embryonic and postnatal MNP and suggest that it regulates the transition from GFAP-expressing progenitors to rapid amplifying progenitors in the postnatal brain

Fate mapping identifies the origin of SHF/AHF progenitors in the chick primitive streak

Heart development depends on the spatio-temporally regulated contribution of progenitor cells from the primary, secondary and anterior heart fields. Primary heart field (PHF) cells are first recruited to form a linear heart tube; later, they contribute to the inflow myocardium of the four-chambered heart. Subsequently cells from the secondary (SHF) and anterior heart fields (AHF) are added to the heart tube and contribute to both the inflow and outflow myocardium. In amniotes, progenitors of the linear heart tube have been mapped to the anterior-middle region of the early primitive streak. After ingression, these cells are located within bilateral heart fields in the lateral plate mesoderm. On the other hand SHF/AHF field progenitors are situated anterior to the linear heart tube, however, the origin and location of these progenitors prior to the development of the heart tube remains elusive. Thus, an unresolved question in the process of cardiac development is where SHF/AHF progenitors originate from during gastrulation and whether they come from a region in the primitive streak distinct from that which generates the PHF. To determine the origin and location of SHF/AHF progenitors we used vital dye injection and tissue grafting experiments to map the location and ingression site of outflow myocardium progenitors in early primitive streak stage chicken embryos. Cells giving rise to the AHF ingressed from a rostral region of the primitive streak, termed region ‘A’. During development these cells were located in the cranial paraxial mesoderm and in the pharyngeal mesoderm. Furthermore we identified region ‘B’, located posterior to ‘A’, which gave rise to progenitors that contributed to the primary heart tube and the outflow tract. Our studies identify two regions in the early primitive streak, one which generates cells of the AHF and a second from which cardiac progenitors of the PHF and SHF emerge.Esther Camp, Susanne Dietrich, Andrea Münsterber

Spinal Progenitor-Laden Bridges Support Earlier Axon Regeneration Following Spinal Cord Injury.

Impact statementSpinal cord injury (SCI) results in loss of tissue innervation below the injury. Spinal progenitors have a greater ability to repair the damage and can be injected into the injury, but their regenerative potential is hampered by their poor survival after transplantation. Biomaterials can create a cell delivery platform and generate a more hospitable microenvironment for the progenitors within the injury. In this work, polymeric bridges are used to deliver embryonic spinal progenitors to the injury, resulting in increased progenitor survival and subsequent regeneration and functional recovery, thus demonstrating the importance of combined therapeutic approaches for SCI

Upper limits on bolometric luminosities of ten type Ia supernova progenitors from Chandra observations

We present an analysis of Chandra observations of the position of ten nearby (< 25 Mpc) type Ia supernovae, taken before the explosions. No sources corresponding to progenitors were found in any of the observations. We calculated upper limits on the bolometric luminosities of the progenitors assuming black-body X-ray spectra with temperatures of 30-150 eV. This is inspired by the fact that luminous super-soft X-ray sources have been suggested as the direct progenitors of type Ia supernovae. The upper limits of two supernovae in our sample are comparable to the luminosities of the brightest observed super-soft sources, ruling out such sources as the progenitors of these supernovae. In contrast to Liu et al (2012) we find that for SN2011fe we can rule out Eddington luminosity systems for black body temperatures as low as 40 eV. Our findings are consistent with statistical studies comparing the observed type Ia supernova rate to the number of super-soft sources or the integrated X-ray luminosity in external galaxies. This suggest that either the progenitors of type Ia supernovae are not accreting, nuclear burning white dwarfs, or that they do not look like the classical super-soft sources, e.g. because they are obscured.Comment: Accepted, MNRAS. 10 pages, 11 figures, 3 table

The Progenitors and Lifetimes of Planetary Nebula

Planetary Nebulae (PNe) are amongst the most spectacular objects produced by stellar evolution, but the exact identity of their progenitors has never been established for a large and homogeneous observational sample. We investigate the relationship between PNe and their stellar progenitors in the Large Magellanic Cloud (LMC) through the statistical comparison between a highly complete spectroscopic catalog of PNe and the spatially resolved age distribution of the underlying stellar populations. We find that most PN progenitors in the LMC have main-sequence lifetimes in a narrow range between 5 and 8 Gyr, which corresponds to masses between 1.2 and 1.0 M$_{\odot}$, and produce PNe that last $26^{+6}_{-7}$~kyr on average. We tentatively detect a second population of PN progenitors, with main-sequence lifetimes between 35 and 800~Myr, i.e., masses between 8.2 and 2.1 M$_{\odot}$, and average PN lifetimes of $11^{+6}_{-7}$ kyr. These two distinct and disjoint populations of progenitors strongly suggest the existence of at least two physically distinct formation channels for PNe. Our determination of PN lifetimes and progenitor masses has implications for the understanding of PNe in the context of stellar evolution models, and for the role that rotation, magnetic fields, and binarity can play in the shaping of PN morphologies.Comment: 6 pages, 3 figures, 1 table. Accepted for publication by ApJ Letter

Olig2/Plp-positive progenitor cells give rise to Bergmann glia in the cerebellum.

NG2 (nerve/glial antigen2)-expressing cells represent the largest population of postnatal progenitors in the central nervous system and have been classified as oligodendroglial progenitor cells, but the fate and function of these cells remain incompletely characterized. Previous studies have focused on characterizing these progenitors in the postnatal and adult subventricular zone and on analyzing the cellular and physiological properties of these cells in white and gray matter regions in the forebrain. In the present study, we examine the types of neural progeny generated by NG2 progenitors in the cerebellum by employing genetic fate mapping techniques using inducible Cre-Lox systems in vivo with two different mouse lines, the Plp-Cre-ER(T2)/Rosa26-EYFP and Olig2-Cre-ER(T2)/Rosa26-EYFP double-transgenic mice. Our data indicate that Olig2/Plp-positive NG2 cells display multipotential properties, primarily give rise to oligodendroglia but, surprisingly, also generate Bergmann glia, which are specialized glial cells in the cerebellum. The NG2+ cells also give rise to astrocytes, but not neurons. In addition, we show that glutamate signaling is involved in distinct NG2+ cell-fate/differentiation pathways and plays a role in the normal development of Bergmann glia. We also show an increase of cerebellar oligodendroglial lineage cells in response to hypoxic-ischemic injury, but the ability of NG2+ cells to give rise to Bergmann glia and astrocytes remains unchanged. Overall, our study reveals a novel Bergmann glia fate of Olig2/Plp-positive NG2 progenitors, demonstrates the differentiation of these progenitors into various functional glial cell types, and provides significant insights into the fate and function of Olig2/Plp-positive progenitor cells in health and disease

Assembly history of subhalo populations in galactic and cluster sized dark haloes

We make use of two suits of ultra high resolution N-body simulations of individual dark matter haloes from the Phoenix and the Aquarius Projects to investigate systematics of assembly history of subhaloes in dark matter haloes differing by a factor of $1000$ in the halo mass. We have found that real progenitors which built up present day subhalo population are relatively more abundant for high mass haloes, in contrast to previous studies claiming a universal form independent of the host halo mass. That is mainly because of repeated counting of the 're-accreted' (progenitors passed through and were later re-accreted to the host more than once) and inclusion of the 'ejected' progenitor population(progenitors were accreted to the host in the past but no longer members at present day) in previous studies. The typical accretion time for all progenitors vary strongly with the host halo mass, which is typical about $z \sim 5$ for the galactic Aquarius and about $z \sim 3$ for the cluster sized Phoenix haloes. Once these progenitors start to orbit their parent haloes, they rapidly lose their original mass but not their identifiers, more than $55$ ($50$) percent of them survive to present day for the Phoenix(Aquarius) haloes. At given redshift, survival fraction of the accreted subhalo is independent of the parent halo mass, whilst the mass-loss of the subhalo is more efficient in high mass haloes. These systematics results in similarity and difference in the subhalo population in dark matter haloes of different masses at present day.Comment: 7 pages, 6 figures, moderate changes, accepted to MNRA

Tendon proper- and peritenon-derived progenitor cells have unique tenogenic properties.

IntroductionMultipotent progenitor populations exist within the tendon proper and peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials.MethodsIsolated progenitors were seeded within fibrinogen/thrombin gel-based constructs with or without supplementation with recombinant growth/differentiation factor-5 (GDF5). Early and late in culture, gene expression of differentiation markers and matrix assembly genes was analyzed. Tendon construct ultrastructure was also compared after 45&nbsp;days. Moreover, conditioned media from tendon proper-derived progenitors, peritenon-derived progenitors, or tenocytes was applied to each of the three cell types to determine paracrine stimulatory effects of the factors secreted from each of the respective cell types.ResultsThe cell orientation, extracellular domain and fibril organization of constructs were comparable to embryonic tendon. The tendon proper-derived progenitors produced a more tendon-like construct than the peritenon-derived progenitors. Seeded tendon proper-derived progenitors expressed greater levels of tenogenic markers and matrix assembly genes, relative to peritenon-derived progenitors. However, GDF5 supplementation improved expression of matrix assembly genes in peritenon progenitors and structurally led to increased mean fibril diameters. It also was found that peritenon-derived progenitors secrete factor(s) stimulatory to tenocytes and tendon proper progenitors.ConclusionsData demonstrate that, relative to peritenon-derived progenitors, tendon proper progenitors have greater potential for forming functional tendon-like tissue. Furthermore, factors secreted by peritenon-derived progenitors suggest a trophic role for this cell type as well. Thus, these findings highlight the synergistic potential of including these progenitor populations in restorative tendon engineering strategies