A5081237375- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Renal and related cancers
- Single-cell and spatial transcriptomics
- Animal Genetics and Reproduction
- Reproductive Biology and Fertility
- Chromosomal and Genetic Variations
- Pancreatic function and diabetes
- Mesenchymal stem cell research
- Vector-Borne Animal Diseases
- Congenital heart defects research
- Biomedical Ethics and Regulation
- Diabetes and associated disorders
- 3D Printing in Biomedical Research
- Genomics and Rare Diseases
- Endoplasmic Reticulum Stress and Disease
- Genetic Associations and Epidemiology
- Tissue Engineering and Regenerative Medicine
- T-cell and Retrovirus Studies
The University of Texas Southwestern Medical Center
2020-2025
Southwestern Medical Center
2024-2025
Howard Hughes Medical Institute
2024
The University of Texas at Dallas
2023
Texas A&M University
2020
Recent advances in human blastoids have opened new avenues for modeling early development and implantation. One limitation of our first protocol blastoid generation was relatively low efficiency. We now report an optimized the efficient large quantities high-fidelity from naive pluripotent stem cells. This enabled proteomics analysis that identified phosphosite-specific signatures potentially involved derivation and/or maintenance signaling states blastoids. Additionally, we uncovered...
Here, we report that a chemical cocktail (LCDM: leukemia inhibitory factor [LIF], CHIR99021, dimethinedene maleate [DiM], minocycline hydrochloride), previously developed for extended pluripotent stem cells (EPSCs) in mice and humans, enables de novo derivation long-term culture of bovine trophoblast (TSCs). Bovine TSCs retain developmental potency to differentiate into mature exhibit transcriptomic epigenetic (chromatin accessibility DNA methylome) features characteristic trophectoderm from...
Perturb-seq is a powerful approach to systematically assess how genes and enhancers impact the molecular cellular pathways of development disease. However, technical challenges have limited its application in stem cell-based systems. Here, we benchmarked across multiple CRISPRi modalities, on diverse genomic targets, human pluripotent cells, during directed differentiation lineages, sgRNA delivery To ensure cost-effective production large-scale datasets as part Impact Genomic Variants...
The bi-functional enzyme FicD catalyzes AMPylation and deAMPylation of the endoplasmic reticulum chaperone BiP to modulate ER homeostasis unfolded protein response (UPR). Human hFicD with an arginine-to-serine mutation disrupts activity resulting in severe neonatal diabetes. We generated mFicDR371S mice create a pre-clinical murine model for observed elevated levels across multiple tissues signature markers diabetes including glucose intolerance reduced serum insulin levels. While pancreas...
Abstract Phenotypic selection during animal domestication has resulted in unwanted incorporation of deleterious mutations. In horses, the autosomal recessive condition known as Glycogen Branching Enzyme Deficiency (GBED) is result one these mutations (102C > A), first exon GBE1 gene ( 102C>A ). With recent advances genome editing, this type genetic mutation can be precisely repaired. study, we used RNA-guided nuclease CRISPR-Cas9 (clustered regularly-interspaced short palindromic...
SUMMARY Recent advances in human blastoids generated from naïve pluripotent stem cells have opened a new avenue for modelling early development and implantation. Despite the success, however, existing protocols several limitations, e.g., use of custom-built microwell arrays impedes wide adoption by research community, mass production is hampered low-output or low-efficiency methods. To address these issues, here we developed an optimized protocol based on commercially available plates, which...
Abstract The seamless transition through stages of pluripotency relies on a delicate balance between transcription factor networks and epigenetic silencing mechanisms that ensure proper regulation the developmental program, critical for normal development. Here, we uncover pivotal role transgene activation suppressor (TASOR), component human hub (HUSH) complex, in sustaining cell viability during from naive to primed pluripotency, despite its rapid downregulation this transition. Loss TASOR...
Abstract Bi-functional enzyme FicD regulates the endoplasmic reticulum chaperone BiP using AMPylation and deAMPylation during ER homeostasis stress, respectively. Human with an arginine-to-serine mutation disrupts activity resulting in severe neonatal diabetes. We generated R371S mice to create a pre-clinical murine model for observed elevated levels across multiple tissues signature markers diabetes including glucose intolerance reduced serum insulin levels. While pancreas of appeared...
Understanding blastocyst formation and implantation is critical for improving farm animal reproduction but hampered by a limited supply of embryos. We developed an efficient method to generate bovine blastocyst-like structures (termed blastoids) via the assembly trophoblast stem cells expanded potential cells. Bovine blastoids resemble blastocysts in morphology, cell composition, single-cell transcriptomes, represent accessible vitro model studying embryogenesis.
Understanding blastocyst formation and implantation is critical for improving farm animal reproduction but hampered by a limited supply of embryos. We developed an efficient method to generate bovine blastocyst-like structures (termed blastoids) via the assembly trophoblast stem cells expanded potential cells. Bovine blastoids resemble blastocysts in morphology, cell composition, single-cell transcriptomes, represent accessible vitro model studying embryogenesis
Reproduction, Fertility and Development is an international journal publishing original research , review comment in the fields of reproduction developmental biology humans, domestic animals wildlife