Rongxin Fang
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Cell Image Analysis Techniques
- Chromosomal and Genetic Variations
- Gene Regulatory Network Analysis
- Cytomegalovirus and herpesvirus research
- Neurogenesis and neuroplasticity mechanisms
- Molecular Biology Techniques and Applications
- RNA and protein synthesis mechanisms
- Animal Genetics and Reproduction
- Pancreatic function and diabetes
- Advanced Fluorescence Microscopy Techniques
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- Machine Learning in Bioinformatics
- Immune cells in cancer
- Error Correcting Code Techniques
University of California, San Diego
2016-2024
Howard Hughes Medical Institute
2020-2024
Harvard University
2020-2024
Ludwig Cancer Research
2016-2023
Beijing Institute of Genomics
2013-2015
Chinese Academy of Sciences
2015
Heidelberg University
2013
University of Cambridge
2013
University of Copenhagen
2013
Research Complex at Harwell
2013
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...
Identification of the cis-regulatory elements controlling cell-type specific gene expression patterns is essential for understanding origin cellular diversity. Conventional assays to map regulatory via open chromatin analysis primary tissues hindered by sample heterogeneity. Single cell accessible (scATAC-seq) can overcome this limitation. However, high-level noise each single profile and large volume data pose unique computational challenges. Here, we introduce SnapATAC, a software package...
Abstract Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in brain 1–3 . With proliferation multi-omics datasets, a major challenge is to validate and integrate results into biological understanding cell-type organization. Here we generated transcriptomes epigenomes from more than 500,000 individual cells mouse primary motor cortex, structure that has an evolutionarily conserved role locomotion. We developed...
The human cerebral cortex has tremendous cellular diversity. How different cell types are organized in the and how organization varies across species remain unclear. In this study, we performed spatially resolved single-cell profiling of 4000 genes using multiplexed error-robust fluorescence situ hybridization (MERFISH), identified more than 100 transcriptionally distinct populations, generated a molecularly defined atlas middle superior temporal gyrus. We further explored cell-cell...
Abstract The mammalian cerebrum performs high-level sensory perception, motor control and cognitive functions through highly specialized cortical subcortical structures 1 . Recent surveys of mouse human brains with single-cell transcriptomics 2–6 high-throughput imaging technologies 7,8 have uncovered hundreds neural cell types distributed in different brain regions, but the transcriptional regulatory programs that are responsible for unique identity function each type remain unknown. Here...
Single-cell technologies measure unique cellular signatures but are typically limited to a single modality. Computational approaches allow the fusion of diverse single-cell data types, their efficacy is difficult validate in absence authentic multi-omic measurements. To comprehensively assess molecular phenotypes cells, we devised single-nucleus methylcytosine, chromatin accessibility, and transcriptome sequencing (snmCAT-seq) applied it postmortem human frontal cortex tissue. We developed...
Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited
Hi-C and chromatin immunoprecipitation (ChIP) have been combined to identify long-range interactions genome-wide at reduced cost enhanced resolution, but extracting information from the resulting datasets has challenging. Here we describe a computational method, MAPS, Model-based Analysis of PLAC-seq HiChIP, process data such experiments interactions. MAPS adopts zero-truncated Poisson regression framework explicitly remove systematic biases in HiChIP datasets, then uses normalized contact...
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...
Highlights•A-to-I RNA editing alters cell-cycle transit by impairing pri-miR-26a maturation•Enforced miR-26a expression reduces BC CML progenitor propagation in vivo•pri-miR-155 downregulation ADAR1 stabilizes MDM2 progenitors•Hyper-editing of 3′ UTR prevents miR-155 binding progenitorsSummaryAdenosine deaminase associated with RNA1 (ADAR1) deregulation contributes to therapeutic resistance many malignancies. Here we show that ADAR1-induced hyper-editing normal human hematopoietic...
Abstract Single-cell Hi-C (scHi-C) analysis has been increasingly used to map chromatin architecture in diverse tissue contexts, but computational tools define loops at high resolution from scHi-C data are still lacking. Here, we describe Single-Nucleus Analysis Pipeline for (SnapHiC), a method that can identify and accuracy data. Using 742 mouse embryonic stem cells, benchmark SnapHiC against number of developed mapping interactions bulk Hi-C. We further demonstrate its use by analyzing...
Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function cell types in brain. Classification neurons also essential manipulate controlled ways understand their variation vulnerability brain disorders. The BRAIN Initiative Cell Census Network (BICCN) an integrated network data-generating centers, archives, standards developers, with goal systematic multimodal type profiling characterization....
Abstract Identification of the cis -regulatory elements controlling cell-type specific gene expression patterns is essential for understanding origin cellular diversity. Conventional assays to map regulatory via open chromatin analysis primary tissues hindered by heterogeneity samples. Single cell transposase-accessible (scATAC-seq) can overcome this limitation. However, high-level noise each single profile and large volumes data could pose unique computational challenges. Here, we introduce...
Abstract Single cell transcriptomics has transformed the characterization of brain identity by providing quantitative molecular signatures for large, unbiased samples populations. With proliferation taxonomies based on individual datasets, a major challenge is to integrate and validate results toward defining biologically meaningful types. We used battery single-cell transcriptome epigenome measurements generated BRAIN Initiative Cell Census Network (BICCN) comprehensively assess types in...
In 2021, the World Health Organization reclassified glioblastoma, most common form of adult brain cancer, into isocitrate dehydrogenase (IDH)-wild-type glioblastomas and grade IV IDH mutant (G4 IDHm) astrocytomas. For both tumor types, intratumoral heterogeneity is a key contributor to therapeutic failure. To better define this heterogeneity, genome-wide chromatin accessibility transcription profiles clinical samples G4 IDHm astrocytomas were analyzed at single-cell resolution. These...