A5100726883- Renal and related cancers
- Pluripotent Stem Cells Research
- Renal cell carcinoma treatment
- Organ Donation and Transplantation
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- 3D Printing in Biomedical Research
- RNA and protein synthesis mechanisms
- Tissue Engineering and Regenerative Medicine
- Biomedical Ethics and Regulation
- Genetic and Kidney Cyst Diseases
- Photoreceptor and optogenetics research
- Nicotinic Acetylcholine Receptors Study
- DNA Repair Mechanisms
- Fusion materials and technologies
- RNA modifications and cancer
- Genetic Syndromes and Imprinting
- Prion Diseases and Protein Misfolding
- Pregnancy and preeclampsia studies
- Molecular Biology Techniques and Applications
- bioluminescence and chemiluminescence research
- Developmental Biology and Gene Regulation
- RNA regulation and disease
University of Southern California
2019-2024
Broad Center
2023-2024
Salk Institute for Biological Studies
2015-2022
Tsinghua University
2012-2015
Institute of Theoretical Physics
2009
Jilin University
2009
Recent studies using human pluripotent stem cells (hPSCs) have developed protocols to induce kidney-lineage and reconstruct kidney organoids. However, the separate generation of metanephric nephron progenitors (NPs), mesonephric NPs, ureteric bud (UB) cells, which constitute embryonic kidneys, in vitro differentiation culture systems has not been fully investigated. Here, we create a system these mesoderm-like cell types paraxial lateral plate are separately generated from hPSCs. We...
Abstract Current kidney organoids model development and diseases of the nephron but not contiguous epithelial network kidney’s collecting duct (CD) system. Here, we report generation an expandable, 3D branching ureteric bud (UB) organoid culture that can be derived from primary UB progenitors mouse human fetal kidneys, or generated de novo pluripotent stem cells. In chemically-defined conditions, generate CD organoids, with differentiated principal intercalated cells adopting spatial...
The number of patients requiring dialysis therapy continues to increase worldwide because the lack effective treatments for chronic kidney disease (CKD). Furthermore, no curative acute injury (AKI) have been established. therapeutic effects human induced pluripotent stem cell–derived nephron progenitor cells (hiPSC-NPCs) on AKI reported in mice but not clinically confirmed. There are also reports examining potential hiPSC-NPCs CKD. Although large numbers uniform required cell therapies and...
To determine the error rate of transcription in human cells, we analyzed transcriptome H1 embryonic stem cells with a circle-sequencing approach that allows for high-fidelity sequencing transcriptome. These experiments identified approximately 100,000 errors distributed over every major RNA species cells. Our results indicate different display rates, suggesting prioritize fidelity some RNAs others. Cross-referencing detected various genetic and epigenetic features genome revealed vivo...
Aging is characterized by the accumulation of proteins that display amyloid-like behavior. However, molecular mechanisms which these arise remain unclear. Here, we demonstrate are produced in a variety human cell types, including stem cells, brain organoids and fully differentiated neurons mistakes occur messenger RNA molecules. Some generate mutant already known to cause disease, while others have not been observed before. Moreover, show increase when cells exposed DNA damage, major...
BMP4 maintains self-renewal of mouse embryonic stem cells (ESCs) in collaboration with LIF. Here, we report the identification a novel key BMP target gene, cochlin (Coch) ESCs. Coch can be significantly up-regulated by specifically ESCs but not somatic differentiated cells, and this up-regulation is dependent on signaling mediators Smad1/5 Smad4. Overexpression partially substitute to promote together LIF, whereas knockdown impairs marker gene expression even presence both Further studies...
Abstract The diverse functions of WASP, the deficiency which causes Wiskott-Aldrich syndrome (WAS), remain poorly defined. We generated three isogenic WAS models using patient induced pluripotent stem cells and genome editing. These recapitulated phenotypes revealed that WASP an upregulation numerous RNA splicing factors widespread altered splicing. Loss binding to factor gene promoters frequently leads aberrant epigenetic activation. interacts with dozens nuclear speckle constituents...
Abstract Is the resonance‐based anionic keto form of oxyluciferin chemical origin multicolor bioluminescence? Can it modulate green into red luminescence? There is as yet no definitive answer from experiment or theory. The forms have been proposed a cause bioluminescence in firefly. We model possible structures by adding sodium ammonium cations and investigating ground‐ excited‐state geometries well electronic absorption emission spectra. A role for resonance obvious gas phase. spectra two...
Stem cell-derived organoids are emerging as sophisticated models for studying development and disease potential sources developing organ substitutes. Unfortunately, although containing renal structures have been generated from mouse human pluripotent stem cells, there still critical unanswered questions that difficult to attain via in vitro systems, including whether these nonvascularized a stable physiologically relevant phenotype or suitable transplantation site long-term vivo studies can...
ABSTRACT Aging is characterized by the accumulation of amyloid and prion-like proteins. However, molecular mechanisms which these proteins arise remain unclear. Here, we demonstrate that transcript errors generate in a wide variety human cell types, including stem cells, brain organoids, fully differentiated neurons. Intriguingly, some are identical to previously implicated familial cases diseases, raising possibility both non-familial caused mutant also have not been observed before,...
Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of kidney. Here we report manipulation p38 YAP activity creates a synthetic niche that allows long-term clonal expansion primary mouse human NPCs, induced NPCs (iNPCs) from pluripotent stem cells. Cultured iNPCs resemble closely generating nephron organoids with abundant distal convoluted tubule cells, which are not observed in published kidney organoids. The reprograms differentiated NPC state,...
Abstract Kidney organoids model development and diseases of the nephron but not contiguous epithelial network kidney’s collecting duct (CD) system. Here, we report generation an expandable, 3D branching ureteric bud (UB) organoid culture that can be derived from primary UB progenitors mouse human fetal kidneys, or generated de novo pluripotent stem cells. differentiate into CD in vitro , with differentiated cell types adopting spatial assemblies reflective adult kidney Aggregating...