排序方式: 共有27条查询结果,搜索用时 15 毫秒
1.
The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway 总被引:3,自引:0,他引:3
Qyang Y Martin-Puig S Chiravuri M Chen S Xu H Bu L Jiang X Lin L Granger A Moretti A Caron L Wu X Clarke J Taketo MM Laugwitz KL Moon RT Gruber P Evans SM Ding S Chien KR 《Cell Stem Cell》2007,1(2):165-179
Isl1(+) cardiovascular progenitors and their downstream progeny play a pivotal role in cardiogenesis and lineage diversification of the heart. The mechanisms that control their renewal and differentiation are largely unknown. Herein, we show that the Wnt/beta-catenin pathway is a major component by which cardiac mesenchymal cells modulate the prespecification, renewal, and differentiation of isl1(+) cardiovascular progenitors. This microenvironment can be reconstituted by a Wnt3a-secreting feeder layer with ES cell-derived, embryonic, and postnatal isl1(+) cardiovascular progenitors. In vivo activation of beta-catenin signaling in isl1(+) progenitors of the secondary heart field leads to their massive accumulation, inhibition of differentiation, and outflow tract (OFT) morphogenic defects. In addition, the mitosis rate in OFT myocytes is significantly reduced following beta-catenin deletion in isl1(+) precursors. Agents that manipulate Wnt signals can markedly expand isl1(+) progenitors from human neonatal hearts, a key advance toward the cloning of human isl1(+) heart progenitors. 相似文献
2.
Cloning, sequencing and heterologous expression of a new chitinase gene, chi92, from Streptomyces olivaceoviridis ATCC 11238 总被引:1,自引:0,他引:1
Haiming Li Hans Plattner Karl-Ludwig Schimz Michael Kieß Hans Diekmann Jochen Meens 《Biotechnology letters》2000,22(15):1203-1209
A new chitinase gene, chi92, encoding the largest known chitinase from Streptomyces olivaceoviridisATCC 11238 was sequenced by means of different PCR-methods. The cloned gene was expressed in E. coliand the recombinant protein could be detected by Western-blot analysis. The multiplicity of chitinolytic enzymes of this strain is discussed. 相似文献
3.
Dietmar Utesch Elvira Molitor Karl-Ludwig Platt Franz Oesch 《In vitro cellular & developmental biology. Animal》1991,27(11):858-863
Summary Cytochrome P-450 dependent hydroxylation of testosterone was measured in 7-day-old cultures of primary rat liver parenchymal
cells. Determinations were carried out in monocultures of parenchymal cells and co-cultures of parenchymal cells with rat
liver nonparenchymal epithelial cells, or mouse embryo fibroblasts.
In the monoculture system, testosterone metabolism was drastically reduced and hardly measurable after 7 days in culture.
In the co-culture systems, individual P-450 isoenzymes were stabilized on different levels. P-450sp and presumablyc were well preserved, P-450a was reduced but clearly measurable, P-450h was totally lost whereas P-450sb ande were not measurable after 7 days (the activities of these isoenzymes however were already low in freshly isolated parenchymal
cells). The results were independent of the cell line used for co-cultivation and of the method of parenchymal cell isolation,
that is whether collagenase or EDTA was used as the agent for dissociating the cells from the liver. The results showed that
the co-cultivation of liver parenchymal cells with other nonparenchymal cells significantly improved the differentiated status
of the former. In this cell culture system however, not every parameter was equally well stabilized. 相似文献
4.
5.
6.
Mathias Orban Alexander Goedel Jessica Haas Kirstin Sandrock-Lang Florian G?rtner Christian Billy Jung Barbara Zieger Elvira Parrotta Karin Kurnik Daniel Sinnecker Gerhard Wanner Karl-Ludwig Laugwitz Steffen Massberg Alessandra Moretti 《PloS one》2015,10(1)
Human induced pluripotent stem cells (hiPSCs) represent a versatile tool to model genetic diseases and are a potential source for cell transfusion therapies. However, it remains elusive to which extent patient-specific hiPSC-derived cells functionally resemble their native counterparts. Here, we generated a hiPSC model of the primary platelet disease Glanzmann thrombasthenia (GT), characterized by dysfunction of the integrin receptor GPIIbIIIa, and compared side-by-side healthy and diseased hiPSC-derived platelets with peripheral blood platelets. Both GT-hiPSC-derived platelets and their peripheral blood equivalents showed absence of membrane expression of GPIIbIIIa, a reduction of PAC-1 binding, surface spreading and adherence to fibrinogen. We demonstrated that GT-hiPSC-derived platelets recapitulate molecular and functional aspects of the disease and show comparable behavior to their native counterparts encouraging the further use of hiPSC-based disease models as well as the transition towards a clinical application. 相似文献
7.
Milena Bellin Simona Casini Richard P Davis Cristina D'Aniello Jessica Haas Dorien Ward‐van Oostwaard Leon G J Tertoolen Christian B Jung David A Elliott Andrea Welling Karl‐Ludwig Laugwitz Alessandra Moretti Christine L Mummery 《The EMBO journal》2013,32(24):3161-3175
Patient‐specific induced pluripotent stem cells (iPSCs) will assist research on genetic cardiac maladies if the disease phenotype is recapitulated in vitro. However, genetic background variations may confound disease traits, especially for disorders with incomplete penetrance, such as long‐QT syndromes (LQTS). To study the LQT2‐associated c.A2987T (N996I) KCNH2 mutation under genetically defined conditions, we derived iPSCs from a patient carrying this mutation and corrected it. Furthermore, we introduced the same point mutation in human embryonic stem cells (hESCs), generating two genetically distinct isogenic pairs of LQTS and control lines. Correction of the mutation normalized the current (IKr) conducted by the HERG channel and the action potential (AP) duration in iPSC‐derived cardiomyocytes (CMs). Introduction of the same mutation reduced IKr and prolonged the AP duration in hESC‐derived CMs. Further characterization of N996I‐HERG pathogenesis revealed a trafficking defect. Our results demonstrated that the c.A2987T KCNH2 mutation is the primary cause of the LQTS phenotype. Precise genetic modification of pluripotent stem cells provided a physiologically and functionally relevant human cellular context to reveal the pathogenic mechanism underlying this specific disease phenotype. 相似文献
8.
Laugwitz KL Moretti A Caron L Nakano A Chien KR 《Development (Cambridge, England)》2008,135(2):193-205
The creation of regenerative stem cell therapies for heart disease requires that we understand the molecular mechanisms that govern the fates and differentiation of the diverse muscle and non-muscle cell lineages of the heart. Recently, different cardiac cell types have been reported to arise from a common, multipotent Islet1 (Isl1)-positive progenitor, suggesting that a clonal model of heart lineage diversification might occur that is analogous to hematopoiesis. The ability to isolate, renew and differentiate Isl1(+) precursors from postnatal and embryonic hearts and from embryonic stem cells provides a powerful cell-based system for characterizing the signaling pathways that control cardiovascular progenitor formation, renewal, lineage specification and conversion to specific differentiated progeny. 相似文献
9.
Pyotr Kisselev Dieter Schwarz Karl-Ludwig Platt Wolf-Hagen Schunck Ivar Roots 《European journal of biochemistry》2002,269(7):1799-1805
Human cytochrome P4501A1 (CYP1A1) is one of the key enzymes in the bioactivation of environmental pollutants such as benzo[a]pyrene (B[a]P) and other polycyclic aromatic hydrocarbons. To evaluate the effect of membrane properties and distinct phospholipids on the activity of human CYP1A1 purified insect cell-expressed human CYP1A1 and of human NADPH-P450 reductase were reconstituted into phospholipid vesicle membranes. Conversion rates of up to 36 pmol x min(-1) x pmol(-1) CYP1A1 of the enantiomeric promutagens (-)- and (+)-trans-7,8-dihydroxy-7,8-dihydro-B[a]P (7,8-diol) to the genotoxic diolepoxides were achieved. The highest rates were obtained when negatively charged lipids such as phosphatidylserine and phosphatidylinositol and/or nonbilayer phospholipids such as phosphatidylethanolamine were present in the membrane together with neutral lipids. Both Vmax and Km values were changed. This suggests a rather complex mechanism of stimulation which might include altered substrate binding as well as more effective interaction between CYP1A1 and NADPH-P450 reductase. Furthermore, the ratio of r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydro-B[a]P (DE2) to r-7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydro-B[a]P (DE1) formed from (-)-7,8-diol was significantly increased by the introduction of anionic lipids, but not by that of nonbilayer lipids. Thus, charged lipids affect the stereoselectivity of the epoxidation by leading to the formation of a larger amount of the ultimate mutagen DE2 than of DE1, which is far less carcinogenic. These data suggest that membrane properties such as negative charge and nonbilayer phase propensity are important for the efficiency and selectivity of enzymatic function of human CYP1A1. 相似文献
10.
Hans-Georg Koch Michael Moser Karl-Ludwig Schimz Matthias Muller 《The Journal of biological chemistry》2002,277(8):5715-5718
The integration of the polytopic membrane protein YidC into the inner membrane of Escherichia coli was analyzed employing an in vitro system. Upon integration of in vitro synthesized YidC, a 42-kDa membrane protected fragment was detected, which could be immunoprecipitated with polyclonal anti-YidC antibodies. The occurrence of this fragment is in agreement with the predicted topology of YidC and probably encompasses the first two transmembrane domains and the connecting 320-amino acid-long periplasmic loop. The integration of YidC was strictly dependent on the signal recognition particle and SecA. YidC could not be integrated in the absence of SecY, SecE, or SecG, suggesting that YidC, in contrast to its mitochondrial orthologue Oxa1p, cannot engage a SecYEG-independent protein-conducting channel. 相似文献