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Gene-expression analysis of human embryonic stem cell (HESC-)- derived rosette-forming neural progenitor cells (NPCs) in the presence of lysophosphatidic acid (LPA)

ABSTRACT: As part of our study on the effect of LPA on HESC-derived NPCs, we have employed whole genome microarray analysis to identify genes which were up- and downregulated in the presence of LPA compared to non-LPA-treated control-NPCs and which might be involved in the expansion of the apical domain of NPCs and large rosette formation that we observe after LPA-treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE111597 | GEO | 2018/03/14

REPOSITORIES: GEO

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Gene-expression analysis of human embryonic stem cell (HESC-)- derived rosette-forming neural progenitor cells (NPCs) in the presence of lysophosphatidic acid (LPA)

Project description:Gene-expression analysis of human embryonic stem cell (HESC-)- derived rosette-forming neural progenitor cells (NPCs) in the presence of lysophosphatidic acid (LPA)

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Influence of lysophosphatidic acid (LPA) and LPA together with interferon tau (IFNt) on transcriptional profiling of bovine endometrial cells.

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Human gingival fibroblasts: control vs. lysophosphatidic acid (LPA 18:1)-treated

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Influence of lysophosphatidic acid (LPA) and LPA together with interferon tau (IFNt) on transcriptional profiling of bovine endometrial cells.

Project description:The endometrium plays a crucial role in the reproductive organs in the aspect of embryo-maternal communication and pregnancy. This study investigated transcriptome profiles of endometrial cells stimulated with PBS, LPA and LPA in combination with IFNt. LPA, one of the signaling molecule, is locally produced and released from the bovine endometrium during estrous cycle and early pregnancy. The highest concentration of LPA and expression of its active receptor (LPAR1) were detected in bovine endometrium at the time of maternal recognition of pregnancy, when the conceptus announces its presence by increased IFNt production. Using transcriptomic approach we compared the influence of LPA and LPA together with IFNt on the gene expression profiles in bovine endometrial cells. A total of nine normally cycling Holstein/Polish Black and White (75/25% respectively) cows were used in this study. Global transcriptional profiling was performed using co-cultured stromal and epithelial cells (ratio - 3:1) isolated from bovine endometrium. Three experimental conditions (control (PBS), LPA and LPA plus IFNt) with three replicates per condition were prepared. Total RNAs were extracted from 9 pooled samples (n=3 for each sample) amplified and hybridized onto Affymetrix microarrays.

2014-01-10 | E-GEOD-53457 | biostudies-arrayexpress

Transcriptomic analysis of human breast and prostate cancer cell lines on lysophosphatidic acid (LPA) stimulation

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Transcriptomic analysis of human breast and prostate cancer cell lines on lysophosphatidic acid (LPA) stimulation

Project description:LPA is a natural bioactive lipid with growth factor-like functions due to activation of series of six G protein-coupled receptors (LPA1-6). In this study we determine the LPA induced early-gene expression profile in three unrelated human cancer cell lines (MDA-MB-231, MCF7, PC3) with an objective to identify potential biomarker/s specifically upregulated through the activation of LPA receptor type 1 (LPA1) MDA-MB-231, MCF7, PC3 cells were serum starved for 24h and then stimulated with LPA (1ÂµM) for 45min. The controls were the serum starved unstimulated cells. Two replicates for each sample were included in this study. Microarray analysis was performed using a high-density oligonucleotide array (GeneChip Human Genome U133 plus 2.0 array, Affymetrix)

2014-05-16 | E-GEOD-56265 | biostudies-arrayexpress

RhoA GEF Mcf2lb regulates rosette integrity during collective cell migration

Project description:During development, multicellular rosettes serve as important cellular intermediates in the formation of diverse organ systems. Multicellular rosettes are transient epithelial structures that are defined by the apical constriction of cells towards the rosette center. Due to the important role these structures play during development, understanding the molecular mechanisms by which rosettes are formed and maintained is of high interest. Utilizing the zebrafish posterior lateral line primordium (pLLP) as a model system, we identify the RhoA GEF Mcf2lb as a regulator of rosette integrity. The pLLP is a group of ~150 cells that migrates along the zebrafish trunk and is organized into epithelial rosettes; these are deposited along the trunk and will differentiate into sensory organs called neuromasts (NMs). Using single-cell RNA sequencing and whole-mount in situ hybridization, we showed that mcf2lb is expressed in the pLLP during migration. Given the known role of RhoA in rosette formation, we asked whether Mcf2lb plays a role in regulating apical constriction of cells within rosettes. Live imaging and subsequent 3D analysis of mcf2lb mutant pLLP cells showed disrupted apical constriction and subsequent rosette organization. This in turn resulted in a unique posterior Lateral Line phenotype: an excess number of deposited NMs along the trunk of the zebrafish. Cell polarity markers ZO-1 and Par-3 were apically localized, indicating that pLLP cells are normally polarized. In contrast, signaling components that mediate apical constriction downstream of RhoA, Rock-2a and non-muscle Myosin II were diminished apically. Altogether our results suggest a model whereby Mcf2lb activates RhoA, which in turn activates downstream signaling machinery to induce and maintain apical constriction in cells incorporated into rosettes.

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Lysophosphatidic acid treatment improves brush border maturation and apical SGLT1 activity in Myo5b deficient mice, a model of MVID

Project description:Myosin Vb (Myo5b) is an essential trafficking protein for membrane recycling in gastrointestinal (GI) epithelial cells and its inactivating mutation causes the congenital diarrheal disease, microvillus inclusion disease (MVID). We previously reported that Myo5b deficiency in mice causes mislocalization of SGLT1 and NHE3, but retained apical function of CFTR, resulting in malabsorption and secretory diarrhea. Activation of lysophosphatidic acid (LPA) receptors can improve diarrhea, but the effects of LPA on MVID symptoms is unclear. We therefore tested whether LPA treatment can ameliorate the epithelial deficits in Myo5b knockout (KO) mice. Methods: Adult tamoxifen-induced, intestine-specific, Myo5b KO (VillinCreERT2;Myo5bflox/flox) and littermate control mice were treated with LPA, an LPAR2 agonist (GRI977143), or vehicle for 4 days after a single tamoxifen injection. Apical SGLT1 and CFTR activities were measured in Üssing chambers. The localization of membrane transporters was evaluated by immunostaining in mouse tissues and enteroids. RNA sequencing and enrichment analysis were performed with isolated jejunal epithelial cells. Results: Daily treatment with LPA decreased the frequency of multivesicular bodies and the expression of cathepsins, but did not affect the formation of microvillus inclusions in Myo5b KO mice. LPA partially restored the brush border height and the localization of SGLT1 and NHE3 in Myo5b KO small intestine and enteroids. SGLT1-dependent short-circuit current (Isc) was increased and abnormal CFTR activities were suppressed in LPA-treated jejunum compared to that of vehicle-treated Myo5b KO mice. Conclusions: Cell autonomous LPA signaling may modulate a Myo5b-independent trafficking mechanism and the brush border maturation, demonstrating a therapeutic potential for LPA in the treatment of MVID.

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2024-01-01 | GSE216735 | GEO

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