Pleiotropic Function of Cellular Prion Protein: Encompassing Endoplasmic-Reticulum Stress, Cell Proliferation in Vascular Smooth Muscle Cells.

Cellular prion protein (PRNP) has been implicated in various physiological processes in different cell types, for decades. Little has been known how PRNP functions in multiple, yet related processes within a particular system. In our current study, with the aid of high-throughput RNA-sequencing technique, we have presented an overall transcriptome profile of rat vascular smooth muscle cells (VSMCs) with Prnp knockdown.

IL1β-NFκβ-Myocardin signaling axis governs trophoblast-directed plasticity of vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) plasticity is fundamental in uterine spiral artery remodeling during placentation in Eutherian mammals. Our previous work showed that the invasion of trophoblast cells into uterine myometrium coincides with a phenotypic change of VSMCs. Here, we elucidate the mechanism by which trophoblast cells confer VSMC plasticity.

Evaluation of Molecular Interactions and Cellular Dynamics at the Maternal-Fetal Interface During Placental Morphogenesis.

Molecular events at the maternal-fetal interface establish successful pregnancies. Identifying and characterizing the heterogeneous cell population and their cross-talk at the cellular and molecular levels are essential to expand our knowledge on the progression and maintenance of pregnancy. In this chapter, we briefly discuss the organization of maternal-fetal interface in mice/rats and humans.

Cellular Prion protein moonlights vascular smooth muscle cell fate: Surveilled by trophoblast cells.

Uterine spiral artery remodeling (uSAR) is a hallmark of hemochorial placentation. Compromised uSAR leads to adverse pregnancy outcomes. Salient developmental events involved in uSAR are active areas of research and include (a) trophendothelial cell invasion into the spiral arteries, selected demise of endothelial cells; (b) de-differentiation of vascular smooth muscle cells (VSMC); and (c) migration and/or death of VSMCs surrounding spiral arteries.

Molecular determinants of epithelial mesenchymal transition in mouse placenta and trophoblast stem cell.

Trophectoderm cells of the blastocyst are the precursor of the placenta that is comprised of trophoblast, endothelial and smooth muscle cells. Since trophoectoderm cells are epithelial in nature, epithelial mesenchymal transition (EMT) of trophoblast stem (TS) cells might play pivotal role in placental morphogenesis. However, the molecular regulation of EMT during placental development and trophoblast differentiation still remained elusive.

Trans-differentiation of trophoblast stem cells: implications in placental biology.

Trophoblast invasion is a hallmark of hemochorial placentation. Invasive trophoblast cells replace the endothelial cells of uterine spiral arteries. The mechanism by which the invasive trophoblast cells acquire this phenotype is unknown.

Tipping the balance toward stemness in trophoblast: Metabolic programming by Cox6B2.

Metabolic effector(s) driving cell fate is an emerging concept in stem cell biology. Here we showed that Cytochrome C Oxidase Subunit 6B2 (Cox6B2) is essential to maintain the stemness of trophoblast stem (TS) cells. RNA interference of Cox6b2 resulted in decreased mitochondrial Complex IV activity, ATP production, and oxygen consumption rate in TS cells.

Protocol for functional characterization of endoreduplicated murine trophoblast cells.

Murine trophoblast stem cells (TSCs) have shaped placental research by providing resources for investigating trophoblast subtype specialization. Trophoblast giant cells (TGCs) are large polyploid cells, which undergo repetitive rounds of DNA replication without intervening mitosis by a process called endoreduplication. Endocrine and paracrine functions of TGCs aid in maternal adaptations to pregnancy.

Nitric-Oxide Synthase trafficking inducer (NOSTRIN) is an emerging negative regulator of colon cancer progression.

Background: NOSTRIN, abundantly expressed in colon, was reported to be anti-angiogenic, anti-invasive and anti-inflammatory. NOSTRIN expression was inversely related to survival of pancreatic ductal adeno-carcinoma patients. Yet its function and regulatory mechanism in CRC remains elusive.

Molecular regulation of trophoblast stem cell self-renewal and giant cell differentiation by the Hippo components YAP and LATS1.

Background: Trophoblast stem cells (TSCs), the precursors of trophoblast cells of placenta, possess the potential to differentiate into various trophoblastic subtypes in vitro. Establishment of extraembryonic trophoblastic lineage is preceded by the "outside versus inside" positional information in preimplantation embryos, critically synchronized by the Hippo components. Abundant expression of Hippo effector YAP in TSCs and differentiated cells with paucity of information on Hippo regulation of TSC proliferation/differentiation led us test the hypothesis that Hippo dynamics is one of the regulators of  TSC proliferation/differentiation.

Sequestration of eIF4A by angiomotin: A novel mechanism to restrict global protein synthesis in trophoblast cells.

Enrichment of angiomotin (AMOT) in the ectoplacental cone of E7.5 murine placenta prompted our investigation on the role of AMOT in trophoblast differentiation. We show here that AMOT levels increased in mouse placenta during gestation and also upon induction of differentiation in trophoblast stem cell ex vivo.

MicroRNA regulation of murine trophoblast stem cell self-renewal and differentiation.

Proper placentation is fundamental to successful pregnancy. Placenta arises from differentiation of trophoblast stem (TS) cells during development. Despite being recognized as the counterpart of ES cells in placental development, the role of regulatory miRNAs in TS cell differentiation remains inadequately explored.

Molecular regulation of vascular smooth muscle cell phenotype switching by trophoblast cells at the maternal-fetal interface.

Introduction: Establishment of hemochorial placenta is associated with development and remodelling of uterine vasculature at the maternal fetal interface. This results in calibration of high resistance uterine arteries to flaccid low resistance vessels resulting in increased blood flow to the placenta and fetus in humans and rodents. Mechanisms underlying these remodelling events are poorly understood.

Harnessing Autophagic Network Is Essential for Trophoblast Stem Cell Differentiation.

Differentiation of trophoblast stem (TS) cells into various cell lineages of the placenta during mammalian development is accompanied by dynamic changes in its proteome for exerting the highly specialized functions of various cell subtypes. In the present study, we demonstrate that the autophagic machinery, which includes proteins for initiation, vesicle nucleation, and autophagosome maturation are robustly upregulated during differentiation of TS cells. Interestingly, basal levels of autophagy were detectable in the developing mouse placenta as well as TS cells.

Regulation of Transcription by Circular RNAs.

Circular RNAs (circRNAs) are a class of noncoding RNA that are present in wide variety of cells in various tissue types across species. They are non-polyadenylated, single-stranded, covalently closed RNAs. CircRNAs are more stable than other RNAs due to lack of 5' or 3' end leading to resistance to exonuclease digestion.

NOSTRIN: A novel modulator of trophoblast giant cell differentiation.

Differentiation-dependent expression of NOSTRIN in murine trophoblast cells prompted investigation on NOSTRIN's function in trophoblast differentiation. We show here that NOSTRIN levels increased in both mouse and rat placenta during gestation. NOSTRIN expression was not co-related to expression of eNOS precluding its eNOS mediated function.

Dexamethasone-induced Intra-Uterine Growth Restriction impacts NOSTRIN and its downstream effector genes in the rat mesometrial uterus.

Intra-Uterine Growth Restriction (IUGR) is a major cause of fetal and neonatal mortality. Understanding the impact of IUGR on utero-placental gene expression is key to developing effective therapy. In this report we elucidated the impact of IUGR on NOSTRIN and its downstream effector gene expression in the utero-placental compartments.

MicroRNA regulation of Transthyretin in trophoblast differentiation and Intra-Uterine Growth Restriction.

Placental trophoblast cells produce various cytokines, transporters vital to normal embryogenesis. Transthyretin (TTR) aids trans-placental passage of maternal thyroxin (TH) to fetal circulation. Inadequate TH delivery leads to developmental abnormality.

Nitric-oxide synthase trafficking inducer is a pleiotropic regulator of endothelial cell function and signaling.

Endothelial nitric-oxide synthase (eNOS) and its bioactive product, nitric oxide (NO), mediate many endothelial cell functions, including angiogenesis and vascular permeability. For example, vascular endothelial growth factor (VEGF)-mediated angiogenesis is inhibited upon reduction of NO bioactivity both and Moreover, genetic disruption or pharmacological inhibition of eNOS attenuates angiogenesis during tissue repair, resulting in delayed wound closure. These observations emphasize that eNOS-derived NO can promote angiogenesis.

Sedative effect of Clozapine is a function of 5-HT and environmental novelty.

Antipsychotic drugs are the mainstay in the treatment of schizophrenia and bipolar disorder. However, antipsychotics often exhibit sedation or activity suppression among many other side effects, and the factors that influence them remain poorly understood. We now show, using a 5-HT knockout (Htr2a) mouse, that environmental circumstances can affect suppression of activity induced by the atypical antipsychotic- Clozapine.

MicroRNA-141-3p and miR-200a-3p regulate insulin-like growth factor 2 during mouse placental development.

Insulin-like growth factor 2 (IGF2) plays a vital role in fetal and placental development throughout gestation. Placental expression of IGF2 decreases substantially in intra-uterine growth restriction (IUGR) and Igf2 null mice develop small placentas. In this report, we examined the role of microRNAs in regulating Igf2 gene expression during mouse placental development.

The rat prolactin gene family locus: species-specific gene family expansion.

In the rat there is a large family of paralogous genes related to prolactin (PRL). Members of the PRL family are expressed in cell- and temporal-specific patterns in the anterior pituitary, uterus, and placenta. An overriding feature of the PRL family is its association with pregnancy.

Hypobaric hypoxia as a tool to study pregnancy-dependent responses at the maternal-fetal interface.

Establishment of proper oxygen and nutrient supply to the fetus is essential for a successful pregnancy. The maternal-fetal interface is the site of vascular modifications, providing a conduit for the delivery of essential nutrients to the developing fetus. Pregnancy-dependent adaptive vascular responses within the uteroplacental compartment can be exaggerated by exposure to a physiological stressor such as hypoxia.

Phenotypic analysis of the rat placenta.

The rat is an important model for studying the biology of trophoblast-uterine development. This chapter describes methods that are useful for the characterization of the rat uteroplacental compartment.

Dexamethasone-induced intrauterine growth restriction impacts the placental prolactin family, insulin-like growth factor-II and the Akt signaling pathway.

Intrauterine growth restriction (IUGR) is a major cause of perinatal death and neonatal morbidity and mortality. There are numerous causes of IUGR. Glucocorticoid-induced IUGR is highly relevant because administration of synthetic glucocorticoids, principally dexamethasone, to women threatened by premature labor is widely used in clinical practice.