A Role for MOSPD1 in Mesenchymal Stem Cell Proliferation and Differentiation.

Mesenchymal stem cells (MSCs) isolated from many tissues including bone marrow and fat can be expanded in vitro and can differentiate into a range of different cell types such as bone, cartilage, and adipocytes. MSCs can also exhibit immunoregulatory properties when transplanted but, although a number of clinical trials using MSCs are in progress, the molecular mechanisms that control their production, proliferation, and differentiation are poorly understood. We identify MOSPD1 as a new player in this process.

Glucocorticoid receptor is required for foetal heart maturation.

Glucocorticoids are vital for the structural and functional maturation of foetal organs, yet excessive foetal exposure is detrimental to adult cardiovascular health. To elucidate the role of glucocorticoid signalling in late-gestation cardiovascular maturation, we have generated mice with conditional disruption of glucocorticoid receptor (GR) in cardiomyocytes and vascular smooth muscle cells using smooth muscle protein 22-driven Cre recombinase (SMGRKO mice) and compared them with mice with global deficiency in GR (GR(-/-)). Echocardiography shows impaired heart function in both SMGRKO and GR(-/-) mice at embryonic day (E)17.

Comparative evaluation of the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 version 2 test using the TaqMan 48 analyzer and the Abbott RealTime HIV-1 assay.

Acceptable precision was achieved in a comparison study of the Abbott RealTime (RT) and Roche CAP/CTM-48 V2 HIV-1 assays, but viral load quantification was under- and overestimated, respectively, compared to the 2nd HIV-1 WHO International Standard. The same quantification patterns were observed for patient cohorts from Africa and the United States.

Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice.

Despite significant advances in identifying signaling molecules that induce cardiogenesis in mammals, the transcription factors that control the onset of cardiac myocyte gene expression have remained elusive. Candidates include the zinc finger transcription factors GATA binding proteins 4 and 6 (GATA4, GATA6). The individual loss of either protein in mice results in lethality prior to the onset of heart development due to defects in the extra-embryonic endoderm; however, when this extra-embryonic deficiency is circumvented using tetraploid embryo complementation, cardiac myocyte differentiation initiates normally.

Development of the mammalian liver and ventral pancreas is dependent on GATA4.

Background: In the mouse, the parenchyma of both the liver and ventral pancreas is specified from adjacent domains of the ventral foregut endoderm. GATA4, a zinc finger transcription factor, is strongly expressed in these endodermal domains and molecular analyses have implicated GATA4 in potentiating liver gene expression during the onset of hepatogenesis. We therefore hypothesized that GATA4 has an integral role in controlling the early stages of pancreatic and liver development.

Deriving and identifying hepatocytes from embryonic stem cells.

The generation of hepatocytes from embryonic stem cells (ESCs) holds considerable promise for basic and applied research. However, the unequivocal identification of hepatocytes in ESC differentiation strategies has been hampered by a lack of hepatocyte-specific markers. Recent studies are beginning to address this issue with the identification of hepatocyte-specific genes and the production of hepatocytes from intermediate cell types like definitive endoderm.

A murine specific expansion of the Rhox cluster involved in embryonic stem cell biology is under natural selection.

Background: The rodent specific reproductive homeobox (Rhox) gene cluster on the X chromosome has been reported to contain twelve homeobox-containing genes, Rhox1-12.

Results: We have identified a 40 kb genomic region within the Rhox cluster that is duplicated eight times in tandem resulting in the presence of eight paralogues of Rhox2 and Rhox3 and seven paralogues of Rhox4. Transcripts have been identified for the majority of these paralogues and all but three are predicted to produce full-length proteins with functional potential.

Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability.

The transcription factor GATA4 is a critical regulator of cardiac gene expression where it controls embryonic development, cardiomyocyte differentiation, and stress responsiveness of the adult heart. Traditional deletion of Gata4 caused embryonic lethality associated with endoderm defects and cardiac malformations, precluding an analysis of the role of GATA4 in the adult myocardium. To address the function of GATA4 in the adult heart, Gata4-loxP-targeted mice (Gata4fl/fl) were crossed with mice containing a beta-myosin heavy chain (beta-MHC) or alpha-MHC promoter-driven Cre transgene, which produced viable mice that survived into adulthood despite a 95% and 70% loss of GATA4 protein, respectively.

GATA6 is essential for embryonic development of the liver but dispensable for early heart formation.

Several lines of evidence suggest that GATA6 has an integral role in controlling development of the mammalian liver. Unfortunately, this proposal has been impossible to address directly because mouse embryos lacking GATA6 die during gastrulation. Here we show that the early embryonic deficiency associated with GATA6-knockout mice can be overcome by providing GATA6-null embryos with a wild-type extraembryonic endoderm with the use of tetraploid embryo complementation.

GATA4 is essential for formation of the proepicardium and regulates cardiogenesis.

The role of GATA4 during the earliest stages of cardiogenesis has not been defined because Gata4 knockout embryos suffer an early developmental arrest caused by deficiencies in extraembryonic visceral endoderm function. We have used tetraploid embryo complementation to rescue these defects and generated clonal embryonic day 9.5 Gata4(-/-) embryos directly from embryonic stem cells.

Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility.

The alpha-fetoprotein gene (Afp) is a member of a multigenic family that comprises the related genes encoding albumin, alpha-albumin, and vitamin D binding protein. The biological role of this major embryonic serum protein is unknown although numerous speculations have been made. We have used gene targeting to show that AFP is not required for embryonic development.