- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Renal and related cancers
- Congenital heart defects research
- Pancreatic function and diabetes
- Virus-based gene therapy research
- Developmental Biology and Gene Regulation
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
- Protein Degradation and Inhibitors
- Wnt/β-catenin signaling in development and cancer
- Epigenetics and DNA Methylation
- Tissue Engineering and Regenerative Medicine
- Reproductive Biology and Fertility
- TGF-β signaling in diseases
- Cancer Genomics and Diagnostics
Children's Medical Research Institute
2019-2025
The University of Sydney
2019-2025
Novo Nordisk Foundation
2024
University of Copenhagen
2024
In early mammalian development, cleavage stage blastomeres and inner cell mass (ICM) cells co-express embryonic extra-embryonic transcriptional determinants. Using a protein-based double reporter we identify an stem (ESC) population that co-expresses the factor GATA6 alongside SOX2. Based on single transcriptomics, find this resembles unsegregated ICM, exhibiting enhanced differentiation potential for endoderm while maintaining epiblast competence. To relate transcription binding in these to...
The rapid growth of single-cell transcriptomic technology has produced an increasing number datasets for both embryonic development and in vitro pluripotent stem cell-derived models. This avalanche data surrounding pluripotency the process lineage specification meant it become increasingly difficult to define specific cell types or states vivo, compare these with differentiation. Here we utilize a set deep learning tools integrate classify multiple datasets. allows definition mouse human...
During embryogenesis, the stringent regulation of Wnt activity is crucial for morphogenesis head and brain. The loss function inhibitor Dkk1 results in elevated activity, ectoderm lineage attributes from anterior epiblast, posteriorisation germ layer tissue towards mesendoderm. modulation signalling may therefore be allocation epiblast cells to progenitors during gastrulation. To test this hypothesis, we examined characteristics stem (EpiSCs) that were derived maintained under different...
The rapid growth of single-cell transcriptomic technology has produced an increasing number datasets for both embryonic development and in vitro pluripotent stem cell derived models. This avalanche data about pluripotency the process lineage specification meant it become increasingly difficult to define specific types or states compare these differentiation. Here we utilize a set deep learning (DL) tools integrate classify multiple datasets. allows definition mouse human embryo types,...
Summary A population of putative mesendoderm progenitor cells that can contribute cellular descendants to both mesoderm and endoderm lineages is identified. These are localized the anterior primitive streak adjacent epiblast E7.0-E7.5 mid-to late-gastrula stage embryos. Lineage tracing in vivo revealed progenitors marked by Mixl1 Mesp1 activity layer. Analysis role transcription factor differentiation mouse stem choice for or cell fate depends on timing activation upon exit from...
Human induced pluripotent stem cells (hiPSC) possess the ability to differentiate into a multitude of cell and tissue types but display heterogeneous propensity differentiation specific lineage. Characterization transcriptome eleven hiPSC lines showed that activation MIXL1 at early stage correlated with higher efficacy in generating definitive endoderm advancing maturation derivatives. Enforced expression endoderm-inefficient hiPSCs enhanced differentiation, suggesting modulation key drivers...
Assays for transposase-accessible chromatin sequencing (ATAC-seq) provides an innovative approach to study status in multiple cell types. Moreover, it is also possible efficiently extract differentially accessible (DACs) regions by using state-of-the-art algorithms (e.g. DESeq2) predict gene activity specific samples. Furthermore, has recently been shown that small dips peaks can be attributed the binding of transcription factors. These dips, known as footprints, used identify...
Summary Allocation of cells to an endodermal fate in the gastrulating embryo is driven by Nodal signaling and consequent activation TGFβ pathway. In vitro methodologies striving recapitulate process endoderm differentiation, however, use family member Activin place Nodal. This despite not known have vivo role differentiation. this study, five epiblast stem cell lines were subjected directed differentiation using both A induce fate. reporter line harboring markers FoxA2 Sox17 was further...