A5066225165- Renal and related cancers
- Renal cell carcinoma treatment
- Genetic and Kidney Cyst Diseases
- Tissue Engineering and Regenerative Medicine
- Organ Donation and Transplantation
- Pluripotent Stem Cells Research
- Pediatric Urology and Nephrology Studies
- Single-cell and spatial transcriptomics
- Birth, Development, and Health
- Craniofacial Disorders and Treatments
- Cleft Lip and Palate Research
- Prenatal Screening and Diagnostics
- Dialysis and Renal Disease Management
- Chronic Kidney Disease and Diabetes
- Acute Kidney Injury Research
- Connective tissue disorders research
Broad Center
2019-2024
University of Southern California
2017-2024
Though an acute kidney injury (AKI) episode is associated with increased risk of chronic disease (CKD), the mechanisms determining transition from to irreversible are not well understood. To extend our understanding renal repair, and its limits, we performed a detailed molecular characterization murine ischemia/reperfusion (IRI) model for 12 months after injury. Together, data comprising RNA-sequencing (RNA-seq) analysis at multiple time points, histological studies, cellular targeted gene...
Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron linked to disease. development initiates around 4 weeks of gestation ends 34-37 gestation. Over this period, a reiterative inductive process establishes complement. Studies have provided insightful anatomic descriptions human development, but limited histologic views are not readily accessible broad audience. In first paper in series providing comprehensive...
Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2+ nephron progenitor cells (NPCs) Foxd1+ interstitial (IPCs) form largely distinct lineage compartments at the onset of metanephric Here, we used method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization, immunolabeling to characterize presumptive NPC IPC developing human kidney. As...
The nephron is the functional unit of kidney, but mechanism formation during human development unclear. We conducted a detailed analysis in humans and mice by immunolabeling, we compared mouse patterning to describe conserved divergent features. created protein localization maps that highlight emerging patterns along proximal–distal axis developing benchmark expectations for functionally important transcription factors, which revealed unanticipated cellular diversity. Moreover, identified...
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...
Abstract Sutures separate the flat bones of skull and enable coordinated growth brain overlying cranium. The coronal suture is most commonly fused in monogenic craniosynostosis, yet unique aspects its development remain incompletely understood. To uncover cellular diversity within murine embryonic suture, we generated single-cell transcriptomes performed extensive expression validation. We find distinct pre-osteoblast signatures between bone fronts periosteum, a ligament-like population...
Analysis of kidney disease-causing genes and pathology resulting from systemic diseases highlight the importance kidney's filtering system, renal corpuscles. To elucidate developmental processes that establish corpuscle, we performed single-nucleus droplet-based sequencing human fetal kidney. This enabled identification nephron, interstitial, vascular cell types together generate Trajectory analysis identified transient gene expression, predicting precursors or mature podocytes express...
Structure and function in the mammalian kidney are organized along a radial axis highlighted by corticomedullary organization regional patterning of collecting system. The arborised epithelium arises through controlled growth, branching commitment Wnt11+ ureteric progenitor cells within cortically localized branch tips until postnatal day 3.
Summary Congenital abnormalities of the kidney and urinary tract are amongst most common birth defects affecting 3% newborns. The human develops over a 30-week period in which nephron progenitor pool gives rise to around million nephrons. To establish framework for nephrogenesis, we spatially resolved stereotypical process by equipotent progenitors generate anlagen, then applied data-driven approaches construct three-dimensional protein maps on anatomical models nephrogenic program. Single...
Mammalian kidneys maintain fluid homeostasis through the cellular activity of nephrons and conjoined collecting system. Each epithelial network originates from distinct progenitor cell populations that reciprocally interact during development. To extend our understanding human mouse kidney development, we profiled chromatin organization (ATAC-seq) gene expression (RNA-seq) in developing kidneys. Data were analyzed at a species level then integrated into common, cross-species multimodal data...
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...
Congenital abnormalities of the kidney and urinary tract are amongst most common birth defects affecting 3% newborns. The human forms around a million nephrons from pool nephron progenitors over 30-week period development. To establish framework for nephrogenesis, we spatially resolved stereotypical process by which equipotent generate anlagen, then applied data-driven approaches to construct three-dimensional protein maps on anatomical models nephrogenic program. Single cell RNA sequencing...
Huang, Biao; Zeng, Zipeng; Li, Hui; Zhang, Chennan; Parvez, Riana; Pastor-Soler, Nuria M.; Hallows, Kenneth R.; Lindström, Nils; McMahon, Andrew P.; Zhongwei; Zhongwei Li Lab. Author Information