A5074303879- Pluripotent Stem Cells Research
- Reproductive Biology and Fertility
- Animal Genetics and Reproduction
- Renal and related cancers
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Ovarian function and disorders
- Epigenetics and DNA Methylation
- Genetic and Kidney Cyst Diseases
- Receptor Mechanisms and Signaling
- Reproductive Health and Technologies
- Cellular Mechanics and Interactions
- Epilepsy research and treatment
- Cardiac electrophysiology and arrhythmias
- Vector-Borne Animal Diseases
- Genetics and Neurodevelopmental Disorders
- Bacterial Genetics and Biotechnology
- Mosquito-borne diseases and control
- Studies on Chitinases and Chitosanases
- Hedgehog Signaling Pathway Studies
- Additive Manufacturing and 3D Printing Technologies
- Advancements in Semiconductor Devices and Circuit Design
- RNA regulation and disease
- Virus-based gene therapy research
Harvard University
2022-2025
QIMR Berghofer Medical Research Institute
2020-2023
The University of Queensland
2014-2019
Crosstalk between cardiac cells is critical for heart performance. Here we show that vascular within human organoids (hCOs) enhance their maturation, force of contraction, and utility in disease modeling. Herein optimize our protocol to generate populations addition epicardial, fibroblast, cardiomyocyte self-organize into in-vivo-like structures hCOs. We identify mechanisms communication endothelial cells, pericytes, fibroblasts, cardiomyocytes ultimately contribute organoid maturation. In...
An in vitro model of human ovarian follicles would greatly benefit the study female reproduction. Ovarian development requires combination germ cells and several types somatic cells. Among these, granulosa play a key role follicle formation support for oogenesis. Whereas efficient protocols exist generating primordial cell-like (hPGCLCs) from induced pluripotent stem (hiPSCs), method has been elusive. Here, we report that simultaneous overexpression two transcription factors (TFs) can direct...
Despite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 dynamically regulated by activity vitro vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 KCNIP1, induces a hyper-potentiation phenotype iPSC-derived human cortical neurons following...
In this study we have reprogrammed dermal fibroblasts from an adult female horse into equine induced pluripotent stem cells (equiPSCs). These equiPSCs are dependent only on leukemia inhibitory factor (LIF), placing them in striking contrast to previously derived that been shown be co-dependent both LIF and basic fibroblast growth (bFGF). a normal karyotype maintained beyond 60 passages. They possess alkaline phosphatase activity express eqNANOG, eqOCT4, eqTERT mRNA. Immunocytochemistry...
Abstract The generation of germline cells from human induced pluripotent stem (hiPSCs) represents a milestone toward in vitro gametogenesis. Methods to recapitulate development beyond primordial germ have relied on long-term cell culture, such as 3-dimensional organoid co-culture for ~four months. Using pipeline with highly parallelized screening, this study identifies combinations TFs that directly and rapidly convert hiPSCs oogonia-like (iOLCs). We demonstrate co-expression five – namely,...
Bipolar disorder (BD) is a severe psychiatric condition marked by episodes of mania and depression, with neurotransmitter imbalance in the midbrain believed to play critical role its pathophysiology. Despite this, there currently no validated model for examining BD-associated molecular changes available. Leveraging recent advances stem cell technology, we developed organoid using human induced pluripotent cells (hiPSCs) from BD patients healthy controls (CTR). To address issues variability...
Abstract STUDY QUESTION Can in vitro maturation (IVM) and developmental competence of human oocytes be improved by co-culture with ovarian support cells (OSCs) derived from human-induced pluripotent stem (hiPSCs)? SUMMARY ANSWER OSC-IVM significantly improves the rates metaphase II (MII) formation euploid Day 5 or 6 blastocyst formation, when compared to a commercially available IVM system. WHAT IS KNOWN ALREADY has historically shown highly variable performance maturing generating strong...
The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions the early embryo, primordial germ line, and cells. retrotransposition also occur neuronal lineage cause somatic mosaicism. Although DNA methylation mediates promoter repression, temporal pattern applied to RC-L1s during neurogenesis unclear. Here, we identified de novo insertion human...
Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM).
Optimization of pluripotent stem cell expansion and differentiation is facilitated by biological tools that permit non-invasive dynamic monitoring pluripotency, the ability to select for an undifferentiated input population. Here we report on generation characterisation clonal human embryonic (HES3, H9) induced lines (UQEW01i-epifibC11) have been stably modified with artificial EOS(C3+) promoter driving expression EGFP puromycin resistance-conferring proteins. We show faithfully reports...
Abstract An in vitro model of human ovarian follicles would greatly benefit the study female reproduction. Ovarian development requires combination germ cells and their supporting somatic cells, known as granulosa cells. Whereas efficient protocols exist for generating primordial cell-like (hPGCLCs) from iPSCs, a method has been elusive. Here we report that simultaneous overexpression two transcription factors (TFs) can direct differentiation iPSCs to granulosa-like We elucidate regulatory...
Summary Cardiac maturation is an important developmental phase culminating in profound biological and functional changes to adapt the high demand environment after birth 1,2 . Maturation of human pluripotent stem cell-derived cardiac organoids (hCO) more closely resemble heart tissue critical for understanding disease pathology. Herein, we profile vivo 3 identify key signalling pathways that drive hCOs 4,5 Transient activation both 5’ AMP-activated kinase (AMPK) estrogen-related receptor...
Horses are susceptible to a number of neurotropic viruses, including West Nile virus (WNV), which is pathogen global significance in both horses and humans. However, there no vitro models with study infectious neuropathic diseases the horse. In an effort redress this, we have generated neurons from equine induced pluripotent stem cells (equiPSCs) that express range cortical neuron-specific markers, addition membrane-bound ligand ephrin B3, plays important role axon guidance as well...
Homozygous nonsense mutations in CEP55 are associated with several congenital malformations that lead to perinatal lethality suggesting it plays a critical role regulation of embryonic development. has previously been studied as crucial regulator cytokinesis, predominantly transformed cells, and its dysregulation is linked carcinogenesis. However, molecular functions during development mammals require further investigation. We have generated Cep55 knockout (Cep55-/-) mouse model which...
Structured Abstract Purpose To determine if rescue in vitro maturation (IVM) of human oocytes can be improved by co-culture with ovarian support cells (OSCs) derived from induced pluripotent stem (hiPSCs). Methods Fertility patients undergoing conventional stimulation for oocyte cryopreservation or IVF donated denuded immature germinal vesicle (GV) and metaphase I (MI) research, which were allocated between either the control intervention cultures. aged 25 to 45 years old under informed...
Abstract Germ cells are the vehicle of human reproduction, arising early in embryonic development and developing throughout adult life until menopause onset women. Primordial germ common precursors germline both sexes, undergoing sexual specification into oogonia or gonocytes which further develop oocytes spermatocytes during development. Methods for recapitulation primordial cell formation have been developed extensively recent decades, but fundamental technical limitations their...
SUMMARY Cardiac injury and dysfunction occur in COVID-19 patients increase the risk of mortality. Causes are ill defined, but could be direct cardiac infection and/or inflammation-induced dysfunction. To identify mechanisms cardio-protective drugs, we use a state-of-the-art pipeline combining human organoids with phosphoproteomics single nuclei RNA sequencing. We an inflammatory ‘cytokine-storm’, cocktail interferon gamma, interleukin 1β poly(I:C), induced diastolic Bromodomain-containing...
Abstract Assisted reproductive technologies (ART) have significantly impacted fertility treatment worldwide through innovations such as in vitro fertilization (IVF) and maturation (IVM). IVM holds promise a technology for women who cannot or do not wish to undergo conventional controlled ovarian stimulation (COS). However, has historically shown highly variable performance maturing oocytes generating with strong developmental capacity. Furthermore, recently reported novel approaches are...
Abstract The generation of germline cell types from human induced pluripotent stem cells (hiPSCs) represents a key milestone toward in vitro gametogenesis, which has the potential to transform reproductive medicine. Methods recapitulate specification have relied on extensive, long term culture methods, most notable is four-month protocol employing xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells. Recently, transcription factor (TF)-based methods demonstrated...