A5010237445- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Renal and related cancers
- Molecular Biology Techniques and Applications
- Genetic Syndromes and Imprinting
- Health, Environment, Cognitive Aging
- Erythrocyte Function and Pathophysiology
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Cell Image Analysis Techniques
- Hemoglobinopathies and Related Disorders
- Folate and B Vitamins Research
- Chronic Kidney Disease and Diabetes
- Nuclear Structure and Function
- Iron Metabolism and Disorders
- Growth Hormone and Insulin-like Growth Factors
- Gene Regulatory Network Analysis
- Neurogenesis and neuroplasticity mechanisms
- Genomics and Chromatin Dynamics
- Cancer, Hypoxia, and Metabolism
University of California, San Diego
2014-2024
California Institute of Technology
2023-2024
La Jolla Bioengineering Institute
2010-2023
Fleet Science Center
2023
Harvard University
2013-2020
University of North Carolina at Chapel Hill
2020
University of Rochester Medical Center
2020
Washington University in St. Louis
2020
University of California System
2020
Salk Institute for Biological Studies
2020
Abstract The primary motor cortex (M1) is essential for voluntary fine-motor control and functionally conserved across mammals 1 . Here, using high-throughput transcriptomic epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys mice, we demonstrate a broadly cellular makeup this region, with similarities that mirror evolutionary distance are consistent between the transcriptome epigenome. core molecular identities neuronal non-neuronal cell types allow us to...
Here we report the generation of a multimodal cell census and atlas mammalian primary motor cortex as initial product BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved morphological electrophysiological properties cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance collective knowledge...
Abstract Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles interactions within tissue neighbourhoods 1 . Here we applied multiple single-cell single-nucleus assays (>400,000 nuclei or cells) spatial imaging technologies to a broad spectrum healthy reference kidneys (45 donors) diseased (48 patients). This has provided high-resolution cellular atlas 51 main types, which include rare previously undescribed...
DNA methylation patterns are altered in numerous diseases and often correlate with clinically relevant information such as disease subtypes, prognosis drug response. With suitable assays after validation large cohorts, associations can be exploited for clinical diagnostics personalized treatment decisions. Here we describe the results of a community-wide benchmarking study comparing performance all widely used methods analysis that compatible routine use. We shipped 32 reference samples to...
There is a need to define regions of gene activation or repression that control human kidney cells in states health, injury, and repair understand the molecular pathogenesis disease design therapeutic strategies. Comprehensive integration expression with epigenetic features regulatory elements remains significant challenge. We measure dual single nucleus RNA chromatin accessibility, DNA methylation, H3K27ac, H3K4me1, H3K4me3, H3K27me3 histone modifications decipher landscape regulation...
Expression of a parathyroid hormone-like protein (PLP), which is associated with hypercalcemia in malignancy, has recently been localized to normal lactating mammary tissue. We examined the possibility an extramammary role PLP by measuring its levels serum and milk women. The radioimmunoassay nonlactating women were indistinguishable [4.2 +/- 1.8 3.6 1.0 pg equivalents (eq) PLP-(1-34) amide per ml, respectively]. As was undetectable some samples, this result does not exclude that lactation...
Generation of human induced pluripotent stem cells (hiPSCs) by the expression specific transcription factors depends on successful epigenetic reprogramming to a state. Although hiPSCs and embryonic (hESCs) display similar epigenome, recent reports demonstrated persistence marks from somatic cell type origin aberrant methylation patterns in hiPSCs. However, it remains unknown whether use different sources, encompassing variable levels selection pressure during reprogramming, influences level...
Biological systems are inherently hierarchal and multiscale in time space. A major challenge of biology is to describe biological as a computational model, which can be used derive novel hypothesis drive experiments leading new knowledge. The constraint-based reconstruction analysis approach has been successfully applied metabolism the macromolecular synthesis machinery assembly. Here, we present first integrated stoichiometric model for Escherichia coli K12 MG1655, describes...
Abstract The primary motor cortex (M1) is essential for voluntary fine control and functionally conserved across mammals. Using high-throughput transcriptomic epigenomic profiling of over 450,000 single nuclei in human, marmoset monkey, mouse, we demonstrate a broadly cellular makeup this region, whose similarity mirrors evolutionary distance consistent between the transcriptome epigenome. core molecular identity neuronal non-neuronal types allowed generation cross-species consensus cell...
Abstract Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, interactions within tissue neighborhoods. We have applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) spatial imaging technologies to a broad spectrum healthy reference (n = 42) kidneys. This has provided high resolution cellular atlas 100 that include rare novel populations. The multi-omic approach provides detailed transcriptomic...
A tumor-derived protein with a spectrum of biologic activities remarkably similar to that parathyroid hormone (PTH) has recently been purified and its sequence deduced from cloned cDNA. This PTH-like (PLP) substantial homology PTH only in the amino-terminal 1-13 region shows little similarity other regions thought be important for binding receptors. In present study, we compared actions two synthetic PLP peptides, PLP-(1-34)amide [Tyr36]PLP-(1-36)amide, those bovine (bPTH)-(1-34) on...
Key Points Targeted DNAm profiling of MDS patient bone marrow mononuclear cells identifies several distinct clusters. Clusters enrich for specific genetic lesions and show differences in survival independent clinical prognostic scoring systems..
ABSTRACT We report the generation of a multimodal cell census and atlas mammalian primary motor cortex (MOp or M1) as initial product BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved morphological electrophysiological properties, cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance...
Developing high-resolution reference maps of disease-susceptible spatial niches is a critical step to mitigating the profound effects lung disease. Here, we present an integrated multimodal single-nucleus human atlas (snHLA) profiling 746,047 nuclei from 49 mapped blocks spanning clinically relevant distal airways, alveoli, and interstitium across 11 healthy adults. Integrating snRNA-seq SNARE-seq2, which co-assays chromatin accessibility gene expression same nucleus, resolved 70 molecularly...