A5051472520- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Renal and related cancers
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- COVID-19 Impact on Reproduction
- Epigenetics and DNA Methylation
- Neuroscience and Neural Engineering
- Prenatal Screening and Diagnostics
- RNA modifications and cancer
- 3D Printing in Biomedical Research
- DNA and Nucleic Acid Chemistry
- Reproductive System and Pregnancy
- Reproductive Biology and Fertility
- Chromosomal and Genetic Variations
Washington University in St. Louis
2019-2025
University of Iowa
2018
Naïve human pluripotent stem cells (hPSCs) provide a unique experimental platform of cell fate decisions during pre-implantation development, but their lineage potential remains incompletely characterized. As naïve hPSCs share transcriptional and epigenomic signatures with trophoblast cells, it has been proposed that the state may have enhanced predisposition for differentiation along this extraembryonic lineage. Here we examined isogenic primed hPSCs. We found can directly give rise to...
Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ("blastoids") that model lineage segregation in pre-implantation embryo. However, extent which blastoids can recapitulate defining features of post-implantation development remains unexplored. Here, we report cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks early development, including epiblast lumenogenesis, rapid expansion and diversification...
The recent derivation of human trophoblast stem cells (hTSCs) provides a scalable in vitro model system placental development, but the molecular regulators hTSC identity have not been systematically explored thus far. Here, we utilize genome-wide CRISPR-Cas9 knockout screen to comprehensively identify essential and growth-restricting genes hTSCs. By cross-referencing our data those from similar genetic screens performed other cell types, as well gene expression early embryos, define...
Highlights•A biallelic, dual-colored fluorescent reporter at the imprinted SNRPN locus in hPSCs•Biallelic expression is rapidly induced during primed-to-naive resetting•Acquisition of biallelic irreversible upon re-priming•ZFP57 overexpression mitigates imprint erasure resettingSummaryNaive human pluripotent stem cells (hPSCs) model pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded naive hPSCs, which represents an important deviation from epiblast...
Naive human embryonic stem cells (hESCs) have been isolated that more closely resemble the pre-implantation epiblast compared to conventional "primed" hESCs, but signaling principles underlying these discrete cell states remain incompletely understood. Here, we describe results from a high-throughput screen using ∼3,000 well-annotated compounds identify essential requirements for naive pluripotency. We report MEK1/2 inhibitors can be replaced during maintenance of pluripotency by targeting...
Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application embryonic stem cells (ESCs). While protein-protein interactions core factors have been identified in mouse ESCs, their interactome human ESCs (hESCs) has not to date explored. Here we mapped OCT4 interactomes naïve primed hESCs, revealing extensive connections mammalian ATP-dependent nucleosome remodeling complexes. In associated with both BRG1 BRM, two paralog ATPases BAF...
ABSTRACT Tandem CAG repeat expansion mutations cause >15 neurodegenerative diseases, where ongoing expansions in patients’ brains are thought to drive disease onset and progression. Repeat length will involve single-stranded DNAs prone form mutagenic DNA structures. However, the involvement of binding proteins (SSBs) prevention or formation instability is poorly understood. Here, we assessed role two SSBs, canonical RPA (RPA1-RPA2-RPA3) related Alternative-RPA (Alt-RPA, RPA1-RPA4-RPA3),...