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Viktor Janzen

Publications and source records attributed to Viktor Janzen.

7 recordsLinked to original sources
PubMed2006

Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro.

The molecular mechanisms that regulate human blood vessel formation during early development are largely unknown. Here we used human ESCs (hESCs) as an in vitro model to explore early human vasculogenesis. We demonstrated that stromal cell-derived factor-1 (SDF-1) and CXCR4 were expressed concurrently with hESC-derived embryonic endothelial differentiation. Human ESC-derived embryonic endothelial cells underwent dose-dependent chemotaxis to SDF-1, which enhanced vascular network formation in Matrigel. Blocking of CXCR4 signaling abolished capillary-like structures induced by SDF-1. Inhibition of the SDF-1/CXCR4 signaling pathway by AMD3100, a CXCR4 antagonist, disrupted the endothelial sprouting outgrowth from human embryoid bodies, suggesting that the SDF-1/CXCR4 axis plays a critical role in regulating initial vessel formation, and may function as a morphogen during human embryonic vascular development.

Animals↗
PubMed2006

Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a.

Stem-cell ageing is thought to contribute to altered tissue maintenance and repair. Older humans experience increased bone marrow failure and poorer haematologic tolerance of cytotoxic injury. Haematopoietic stem cells (HSCs) in older mice have decreased per-cell repopulating activity, self-renewal and homing abilities, myeloid skewing of differentiation, and increased apoptosis with stress. Here we report that the cyclin-dependent kinase inhibitor p16INK4a, the level of which was previously noted to increase in other cell types with age, accumulates and modulates specific age-associated HSC functions. Notably, in the absence of p16INK4a, HSC repopulating defects and apoptosis were mitigated, improving the stress tolerance of cells and the survival of animals in successive transplants, a stem-cell-autonomous tissue regeneration model. Inhibition of p16INK4a may ameliorate the physiological impact of ageing on stem cells and thereby improve injury repair in aged tissue.

Aging↗
PubMed2005

The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment.

Bone-marrow-derived cells can contribute nuclei to skeletal muscle fibers. However, serial sectioning of muscle in mdx mice implanted with GFP-labeled bone marrow reveals that only 20% of the donor nuclei chronically incorporated in muscle fibers show dystrophin (or GFP) expression, which is still higher than the expected frequency of "revertant" fibers, but there is no overall increase above controls over time. Obviously, the vast majority of incorporated nuclei either never or only temporarily turn on myogenic genes; also, incorporated nuclei eventually loose the activation of the beta-actin::GFP transgene. Consequently, we attempted to enhance the expression of dystrophin. In vivo application of the chromatin-modifying agents 5-azadeoxycytidine and phenylbutyrate as well as local damage by cardiotoxin injections caused a small increase in dystrophin-positive fibers without abolishing the appearance of "silent" nuclei. The results thus confirm that endogenous repair processes and epigenetic modifications on a small-scale lead to dystrophin expression from donor nuclei. Both effects, however, remain below functionally significant levels.

Actins↗
PubMed2005

Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis.

The zinc finger transcription factor GATA-2 plays a fundamental role in generating hematopoietic stem-cells in mammalian development. Less well defined is whether GATA-2 participates in adult stem-cell regulation, an issue we addressed using GATA-2 heterozygote mice that express reduced levels of GATA-2 in hematopoietic cells. While GATA-2+/- mice demonstrated decreases in some colony-forming progenitors, the most prominent changes were observed within the stem-cell compartment. Heterozygote bone marrow had a lower abundance of Lin(-)c-kit(+)Sca-1(+)CD34- cells and performed poorly in competitive transplantation and quantitative week-5 cobblestone area-forming cell (CAFC) assays. Furthermore, a stem-cell-enriched population from GATA1+/- marrow was more quiescent and exhibited a greater frequency of apoptotic cells associated with decreased expression of the anti-apoptotic gene Bcl-xL. Yet the self-renewal potential of the +/- stem-cell compartment, as judged by serial transplantations, was unchanged. These data indicate compromised primitive cell proliferation and survival in the setting of a lower GATA-2 gene dose without a change in the differentiation or self-renewal capacity of the stem-cells that remain. Thus, GATA-2 dose regulates adult stem-cell homeostasis by affecting select aspects of stem cell function.

Animals↗
PubMed2005

Cellular retinoic acid-binding protein 2 is down-regulated in prostate cancer.

Prostate cancer is among the most frequent tumours in industrialized nations and many questions remain open concerning the molecular events underlying its development and progression. In the present study we have combined cDNA array hybridization to laser-assisted microdissection (LAM) in order to investigate differences in gene expression between epithelial and stromal cells of prostate cancer and normal peripheral prostate tissue. Results have been verified for selected candidate genes by quantitative real-time RT-PCR. Using this approach and immunohistochemistry we could demonstrate a down-regulation of cellular retinoic acid binding protein 2 (CRABP2) mRNA and protein in carcinoma cells compared to normal glandular cells. CRABP2 is a main regulator of anti-carcinogenic activities of retinoic acid and may become a novel diagnostic marker and experimental therapeutic tool for prostate cancer. In addition, results of cDNA array hybridization suggest an up-regulation of 34 further genes and a down-regulation of 6 genes in cancer tissues compared to normal peripheral prostate tissues. Several of these genes have already been reported to be associated with carcinogenesis in organs such as the prostate.

Aged↗
PubMed2003

Influence of histochemical stains on quantitative gene expression analysis after laser-assisted microdissection.

Laser-assisted microdissection (LAM) allows isolation of specific cell populations for molecular studies. The combination of LAM and of real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) enables generation of quantitative cell-specific gene expression data. Histochemical stains used to identify cells desired for LAM should provide acceptable morphology and not interfere with RNA or with subsequent molecular analysis techniques. To determine a reliable stain for analysing RNA, using the housekeeping gene, RPL13A, we performed quantitative gene expression analysis of laser microdissected cells from prostatic frozen tissues. The frozen sections were histochemically stained with hematoxylin, methyl green, toluidine blue O and May-Grunwald. After laser microdissection real-time quantitative RT-PCR was performed. Methyl green yielded more RT-PCR product than did the other dyes. The lowest yield of amplification was obtained after May-Grunwald staining. Therefore we recommend methyl green for general use in gene expression analysis, especially when handling small amounts of RNA.

Ethidium↗