- Pregnancy and preeclampsia studies
- Reproductive System and Pregnancy
- Renal and related cancers
- Neonatal Respiratory Health Research
- Prenatal Screening and Diagnostics
- Birth, Development, and Health
- Congenital Diaphragmatic Hernia Studies
- Gestational Trophoblastic Disease Studies
- Kruppel-like factors research
- Epigenetics and DNA Methylation
- Maternal and fetal healthcare
- Gestational Diabetes Research and Management
- Congenital heart defects research
- Herpesvirus Infections and Treatments
- Genetic Syndromes and Imprinting
- Pluripotent Stem Cells Research
- Hippo pathway signaling and YAP/TAZ
- Endometriosis Research and Treatment
- Reproductive Biology and Fertility
- Uterine Myomas and Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- TGF-β signaling in diseases
- Contact Dermatitis and Allergies
Medical University of Vienna
2016-2025
Henry Ford Hospital
2000
Washington State University
1970-1971
Human trophoblast stem cells (hTSCs) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the placenta. However, access human embryos placentas is limited, thus preventing establishment of hTSCs diverse genetic backgrounds associated with placental disorders. Here, we show that can be generated numerous using post-natal via two alternative methods: (1) somatic cell reprogramming adult fibroblasts OCT4, SOX2, KLF4, MYC (OSKM) (2) fate...
Significance Progenitor trophoblast cells of the human placenta either fuse to form a syncytium or develop into invasive trophoblasts invading maternal uterus. However, regulatory pathways controlling their development and distinct differentiation programs are poorly understood. In present study, we demonstrate that Notch1 is critical regulator early pregnancy, promoting invasive, extravillous lineage survival its progenitors. vivo, detected in progenitors clusters villous initiating...
Various pregnancy complications, such as severe forms of preeclampsia or intrauterine growth restriction, are thought to arise from failures in the differentiation human placental trophoblasts. Progenitors latter either develop into invasive extravillous trophoblasts, remodeling uterine vasculature, fuse multinuclear syncytiotrophoblasts transporting oxygen and nutrients growing fetus. However, key regulatory factors controlling trophoblast self-renewal have been poorly elucidated. Using...
The human endometrium is the inner lining of uterus consisting stromal and epithelial (secretory ciliated) cells. It undergoes a hormonally regulated monthly cycle growth, differentiation, desquamation. However, how these cyclic changes control balance between secretory ciliated cells remains unclear. Here, we established endometrial organoids to investigate estrogen (E2)-driven cell fate decisions in epithelium. We demonstrate that they preserve structure, expression patterns, properties,...
Abnormal placentation has been noticed in a variety of pregnancy complications such as miscarriage, early-onset preeclampsia, and fetal growth restriction. Defects the developmental program extravillous trophoblasts (EVTs), migrating from placental anchoring villi into maternal decidua its vessels, is thought to be an underlying cause. Yet, key regulatory mechanisms controlling commitment differentiation invasive trophoblast lineage remain largely elusive. Herein, comparative gene expression...
Invasion of cytotrophoblasts (CTBs) into uterine tissues is essential for placental development. To identify molecules regulating trophoblast invasion, mRNA signatures purified villous (CTB, poor invasiveness) and extravillous trophoblasts (EVTs) (high isolated from first trimester human placentae explant cultures, respectively, were compared using GeneChip analyses yielding 991 invasion/migration-related transcripts. Several genes involved in physiological pathological cell including A...
The pleiotropic cytokine interleukin-1β (IL-1β) can promote physiological cell migration, as well cancer invasion and metastasis. Its role in human trophoblast invasion, however, has not been satisfactorily answered since direct, indirect no effects on motility have published. Therefore, the of IL-1β re-evaluated by exclusively using primary model systems. Immunofluorescence first trimester placentae indicated IL-1 receptor 1 (IL-1R1) protein expression villous cytotrophoblasts (vCTB)...
lo , have a specific transcriptome, and proliferate in situ d decBAMs are inefficient APCs, induce Tregs, secrete IL-
Formation of migratory extravillous trophoblasts (EVTs) is critical for human placentation and hence embryonic development. However, key regulatory growth factors, hormones, nuclear proteins controlling the particular differentiation process remain poorly understood. Here, role Wingless (Wnt)-dependent transcription factor T-cell factor-4 (TCF-4) in proliferation motility was investigated using different trophoblast cell models. Immunofluorescence first-trimester placental tissues revealed...
Significance The human placenta contains progenitors that give rise to highly specialized trophoblast cell types, and failures in their differentiation are associated with placental pathologies. Importantly, transcription factors controlling these fate decisions humans poorly understood. Here, we uncovered MSX2 as a human-specific regulator of identity implicate its role development disease. We found interacts cobinds many target genes components the SWI/SNF chromatin remodeling complex,...
BACKGROUND: Preeclampsia is a severe hypertensive disorder in pregnancy that causes preterm delivery, maternal and fetal morbidity, mortality, life-long sequelae. Understanding the pathogenesis of preeclampsia critical first step toward protecting mother child from this syndrome increased risk cardiovascular disease later life. However, effective early predictive tests therapies for are scarce. METHODS: To identify novel markers signaling pathways onset preeclampsia, we profiled human...
Growth factors expressed at the fetal-maternal interface modulate hormone expression of placental trophoblasts. The aim this study was to investigate effects different cytokines on hCG subunit mRNA in differentiating villous cytotrophoblasts. Quantitative real-time PCR revealed a 1.8- and 6.9-fold increase hCG-alpha hCG-beta levels, respectively, between 36 60 h term trophoblast syncytialization. Compared with controls, neither interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, IL-13 IL-15 nor...
Abstract Background Heme Oxygenase-1 (HO-1) is expressed in many cancers and promotes growth survival of neoplastic cells. Recently, HO-1 has been implicated tumor cell invasion metastasis. However, the molecular mechanisms underlying these biologic effects remain largely unknown. To identify a common mechanism action cancer, we determined global effect on transcriptome multiple entities identified universal HO-1-associated gene expression signature. Results Genome-wide profiling expressing...
Failures in human extravillous trophoblast (EVT) development could be involved the pathogenesis of pregnancy diseases. However, underlying mechanisms have been poorly characterized. Here, we provide evidence that Notch signaling represent a key regulatory pathway controlling proliferation, motility, and differentiation. Immunofluorescence first-trimester placental tissues revealed expression receptors (Notch2 Notch3) membrane-anchored ligands (delta-like ligand [DLL] 1 -4 Jagged [JAG] -2)...
The basic helix-span-helix transcription factor activating protein (AP)-2α is critically involved in cell-specific hormone expression of syncytializing human trophoblasts. Its role invasive trophoblast differentiation, however, remains largely elusive. Using RT-PCR, Western blotting, and immunofluorescence first-trimester placentae, we here show that AP-2α expressed extravillous trophoblasts (EVTs) both situ vitro as well cell lines. was increased upon supplementation epidermal growth (EGF)...
ADAM12, consisting of a membrane-bound (ADAM12L) and secreted (ADAM12S) form, is expressed exclusively in regenerating developing tissue as well certain cancer types. Strong ADAM12 expression levels have been noticed the human placenta, deregulated ADAM12S were associated with various pregnancy-related disorders including pre-eclampsia intrauterine growth restriction. However, role trophoblast motility has not investigated so far. Hence, present study aimed to investigate specific function...
Failures in growth and differentiation of the early human placenta are associated with severe pregnancy disorders such as pre-eclampsia fetal restriction. However, regulatory mechanisms controlling development placental epithelial cells, trophoblasts, remain poorly elucidated. Using trophoblast stem cells (TSCs), organoids (TB-ORGs) primary cytotrophoblasts (CTBs) pregnancy, we herein show that autocrine NOTCH3 signalling controls expansion differentiation. The receptor was specifically...
Do trophoblast subtypes differ in their expression of erythroblastic leukaemia viral oncogene homologue (ERBB) receptor family members and responsiveness towards specific growth factor ligands? Our data reveal a reciprocal pattern epidermal (EGFR)/ERBB4 proliferative ERBB2/ERBB3 invasive subtypes, as well restricted to (EGF) heparin-binding (HB)-EGF. EGFR is expressed by villous cytotrophoblasts (vCTBs), but absent from extravillous trophoblasts (EVTs), which specifically up-regulate ERBB2....