Moraga Biotech Blog http://moragabiotech.com/nucleus/ en-us Nucleus CMS v3.23 © Weblog http://backend.userland.com/rss http://moragabiotech.com/nucleus//nucleus/nucleus2.gif Moraga Biotech Blog http://moragabiotech.com/nucleus/ BMP Signaling Promotes Proepicardial Protrusion Necessary for Recruiting Epicardial Progenitors to the Heart http://moragabiotech.com/nucleus/index.php?itemid=996 Developmental Cell, Y. Ishii et al. from the Univ. of Calif., San Francisco reported their observations on the expression of BMP ligands in the embryonic myocardium regulate the migration of epicardial progenitors to the heart. The investigators noted that the extracardiac rudiment, the procardium, gives rise to corOnonary vessels and the epicardium of the heart during development. The mechanism in which the procardium protrudes toward and attaches to the looping heart tube appears to be mediated by ecotopic expression of BMP 2/4. The study data demonstrated that misexpression of the BMP ligands suppresses proepicardium protrusion in the developing heart whcih results in mislocation of proepicardium attachment. Further, the BMP antagonist, Noggin, suppresses proepicardium protrusion. Co-culture experiments revealed that procardium explants preferentially expands toward the heart segment expressing BMP 2/4. The authors concluded that their study results support their model "in which myocardium-derived BMP signals regulate the entry of coronary progenitors to the specific site of the heart by directing their morphogenetic movement."
]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=996 Wed, 1 Sep 2010 15:47:00 -0700 Role of miRNAs in the Maintenance of Extraembryonic Stem Cells During Early Development in the Mouse Embryo http://moragabiotech.com/nucleus/index.php?itemid=998 Developmental Cell, T. Spruce et al. from the Imperial College of London reported their study results on the role of miRNAs in the maintenance of embryonic stem cells during very early development of the mouse embryo (i.e. embryonic, epiblast, trophoblast, and primitive endoderm). The investigators found that in the miRNA inhibit apoptosisin pluripotent epiblasts by blocking the expression of the pro-apoptotic protein Bcl2l11 (Bim). The study data also demonstrated that miRNAs maintain the trophoblast stem cell compartment by inhibiting expression of Cdkn1a (p21). Additionally, blocking the expression of Mapk inhibitors by miRNAs maintains the phosphorylated state of ERK1/2 and preventing differentiation. The authors concluded that "there are fundamental differences in how stem cells maintain their developmental potential in embryonic and extraembryonic tissues through miRNAs."
]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=998 Mon, 30 Aug 2010 16:36:00 -0700 Canonical Wnt/β-Catenin Regulation of Liver Receptor Homolog-1 Mediates Pluripotency Gene Expression http://moragabiotech.com/nucleus/index.php?itemid=1004 reported in the August 23rd online edition of Stem Cells their experimental findings on an alternative signaling pathway that regulates pluripotency in embryonic stem cells (ESCs). Pluripotency in vitro is maintained by LIF (leukemia inhibitory factor) which stimulates two signaling axes, i.e. Stat3/Klf4/Sox2 and PI3K/Tbx3/Nanog. The researchers found that their experimental data revealed that the liver receptor homolog-1 (Lrh-1) protein targets β-catenin which in turn directly regulates Nanog. The researchers noted that Lrh-1 is not only responsible for Oct4 expression, but that is was also responsible for maintaining proper levels of Nanog and Tbx3. The authors concluded that elucidation of the Lrh-1 regulator pathway "provides an alternative mechanism by which the primary pluripotency axis may be regulated in vivo, and may pave the way for small molecule applications to manipulate pluripotency, or improved the efficiency of somatic cell reprogramming."]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=1004 Wed, 25 Aug 2010 16:46:00 -0700 High Efficiency Induction of Neural Conversion in hESCs adn hiPSCs with a Single Chemical Inhibitor of the TGF-β Superfamily Receptors http://moragabiotech.com/nucleus/index.php?itemid=1002 reported their experimental findings in identifying a protein kinase inhibitor, compound C, which appears to be a potent regulator of fate decisions for both human embryonic stem cells (hESCS) as well as human induced pluripotent stem cells (hiPSCs). Compound C suppresses differentiation of mesoderm, endoderm, and trophoectoderm while inducing, with a high efficiency, neural conversion in both hESCs and hiPSCs (88.7% and 70.4 %, respectively). The investigators found that compound C targets at least 7 TGF-β superfamily receptors, and thus, blocks both Activing and BMP signaling in hESCs. The researchers also found that compound C targets a homeobox gene 2 (MSX2) downstream which is an intermediate in the BMP signaling pathway in hESCs. The authors concluded that their study results "provide a single-step cost-effective method for efficient derivatlon of neural progenitors cells in adherent culture from human pluripotent stem cells."
]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=1002 Mon, 23 Aug 2010 16:41:00 -0700 Neural Induction Intermediates Mediated by FGF Signaling http://moragabiotech.com/nucleus/index.php?itemid=1001 Stem Cells, Germany scientists from the Max Planck Institute for Molecular Biomedicine (Munster), J. Sterneckert et al., reported their study results on FGF (fibroblast growth factor) signaling mediating the induction of embryonic stem cells (ESCs) committing to a neural lineage. In vitro experiments demonstrated that neural commitment required the ESCs to differentiate into epiblast cells which required FGF signaling. Additionally, FGF2 was found to formation to inhibit neurogenesis via epiblastic intermdeiates while promoting transient self-renewal in the epiblastic stem cells in a dose-dependent fashion. On the other hand, FGF8, a known endogenous, was not able to promote epiblastic self-renewal but it could transient self-renewal of early neural stem cells. Inhibiting FGF in epiblast cells promotes rapid neural induction and subsequent neurogenesis. The authors concluded that "FGF signaling plays different roles during the differentiation of ES cells, with an initial requirement in epiblast formation and subsequent epiblast formation" as well as having an important role in self-renewal.]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=1001 Fri, 20 Aug 2010 16:40:00 -0700 Germline Self-Renewal Requires Cyst Stem Cells and Stat Regulates Niche Adhesion in Drosophila Testes http://moragabiotech.com/nucleus/index.php?itemid=990 reported in a letter in August issue of Nature Cell Biology, that maintenance of germline stem cells in the testes of Drosophila is maintained by somatic cyst stem cells (CySCs). The investigators provided experimental data showing that chemokine activation of STAT does not regulate self-renewal of the germline stem cells (GSCs), but promotes its adhesion to hub cells within the niche. The study results also revealed that GSC self-renewal does not require the presence of hub cells, but is dependent upon cell-cell contact with CySCs via BMP signaling. The researchers suggested that the paradigm in which the presence of hub cells within the Drosophila testes for GSC self-renewal needs to be modified in which they serve to provide the architecture of the niche as well as drawing other cellular components to the stem cell compartment necessary for niche function. The authors concluded that hub cells and CySCs share the function for maintaining GSC self-renewal in which the "niche can coordinate the production of distinct lineages by having one stem cell type rely on a second."
]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=990 Thu, 12 Aug 2010 10:28:00 -0700 SDF-1/CXCR4 Signaling Modulates Neuroprogenitors Homing and Exiting the Vascular Niche http://moragabiotech.com/nucleus/index.php?itemid=988 Cell Stem Cell, E. Kokovay et al. from the Rensselaer Polytechnic Institute (New York) reported the results of their study on the ability of the chemokine, CXCR4 , and its ligand SDF-1 (stromal derived factor 1), modulates the neural stem cells within the vascular niche of the subventricular zone (SVZ) of the adult mouse brains. The investigators conducted experiments demonstrating that neural progenitors cells home to endothelial cells expressing SDF-1 concomitant with upregulation of EGFR (epidermal growth factor receptor) and a6 integrin in two subpopulations of neural progenitor cells (type B self-renewing neural stem cells and their progeny categorized as a type C transit-amplifying subpopulation). CXCR4 signaling enhances the activated state of the neural stem cells as well as the ability to bind laminin within the vascular niche. The researchers also found that SDF-1 enhances the motility of type A neuroblasts, which provides for the cells to migrate from the SVZ to the olfactory bulb. The authors concluded that "differential responses to SDf-1 can regulate progenitor cell occupancy and exit from the adult SVZ vascular niche." ]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=988 Tue, 10 Aug 2010 09:25:00 -0700 MicroRNA Enriched Hematopoietic Stem Cells Differentially Regulate Long-Term Hematopoietic Output http://moragabiotech.com/nucleus/index.php?itemid=986 PNAS, R. M. O'Connell et al. from California Institute of Technology reported their study results on identifying a unique set of microRNAs which have a regulatory role in hematopoietic stem cells (HSCs) during hematopoiesis. The experimental data revealed that the expression of 3 miRNAs appeared to confer a competitive engraftment advantage following transplantation in mice. Conversely, the investigators identified other miRNAs which appeared to suppress red blood cell production. Interestingly, the study results demonstrated that miR-125-b had a dual role in modulating hematopoiesis in HSCs. Mild levels of miR-125b expression appeared to elevate the production of mature red blood cells, whereas overexpression and elevated levels of miR-125b resulted in an aggressive form of myeloid leukemia in mice. The authors concluded from their experimental observations that they had identified "an evolutionarily conserved subset of miRNAs that is expressed in HSCs and functions to modulate hematopoietic output."
]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=986 Thu, 5 Aug 2010 08:42:00 -0700 Nanog Regulates Primordial Germ Cell Migration Through CXCR-4b http://moragabiotech.com/nucleus/index.php?itemid=981 Stem Cells, A. V. Sánchez-Sánchez et al. from the Universidad de Valencia (Spain) published their study results on genes responsible for specification and migration of primordial germ cells (PGCs) during gonadal development in vertebrates. The investigators found that the pluripotency gene, medaka Nanog (Ol-Nanog), is expressed in developing PGCs and regulates the expression of CXCR-4b by binding to its promoter region. PGC migration is guided by CXCR-4b receptor expression and binding to its ligand SDF-1a. The experimental data revealed that depletion of the Ol-Nanog protein results in aberrant migration of PGCs as well as downregulating the expression of CXCR-4b. Similarily, overexpression of CXCR-4b and depletion of Ol-Nanog protein can rescue defective migration, whereas, overexpression of SDF-1a cannot restore proper PGC migration. The authors concluded that their results "indiciate that Ol-Nanog mediates PGC migration by regulating CXCR-4b expression."]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=981 Tue, 13 Jul 2010 10:38:00 -0700 Jarid2 Required for Multi-Lineage Differentiation of Embryonic Stem Cells http://moragabiotech.com/nucleus/index.php?itemid=973 Nature Cell Biology, D. Landiera et al. from the Imperial College School of Medicine (London, UK) reported in a letter their study results on identifying a novel subunit of the polycomb repressor complex 2 (PRC2), Jarid2, which regulates development/differentiation of mouse embryonic stem cells (ESCs). The investigators found that in Jarid2-deficient ESCs there were reduced histone methylation (HEK4me2/me3 and H3K27 me3) which mark recruitment of PRC1/PRC2. Additionally, lost of Jarid2 resulted in a reduced presence of phosphorlyated (Ser5P) RNA polymerase II (RNAP) at the target genes. This observation suggests that Jarid2 has role in also recruiting RNAP to the bivalent genes. The researchers also found ESCs lacking Jarid2 were severely compromised in their ability to differentiate into neural and mesodermal lineages. These mutant cells lack the ability to activated lineage-specific gene expression. The authors concluded from their observation "that transcriptional priming of bivalent genes in pluripotent ES cells is Jarid2-dependent, and suggests that priming is critical for subsequent multi-lineage differentiation."]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=973 Tue, 22 Jun 2010 14:06:38 -0700
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