Project description:Characterizing and interpreting heterogeneous mixtures at the cellular level is a critical problem in genomics. Single-cell assays offer an opportunity to resolve cellular level heterogeneity, e.g., scRNA-seq enables single-cell expression profiling, and scATAC-seq identifies active regulatory elements. Furthermore, while scHi-C can measure the chromatin contacts (i.e., loops) between active regulatory elements to target genes in single cells, bulk HiChIP can measure such contacts in a higher resolution. In this work, we introduce DC3 (De-Convolution and Coupled-Clustering) as a method for the joint analysis of various bulk and single-cell data such as HiChIP, RNA-seq and ATAC-seq from the same heterogeneous cell population. DC3 can simultaneously identify distinct subpopulations, assign single cells to the subpopulations (i.e., clustering) and de-convolve the bulk data into subpopulation-specific data. The subpopulation-specific profiles of gene expression, chromatin accessibility and enhancer-promoter contact obtained by DC3 provide a comprehensive characterization of the gene regulatory system in each subpopulation.
Project description:By utilizing single-cell analysis of neurons that are produced at day 9 of mESC differentiation period (day 9) under the developmentally relevent signals- Retinoic acid and BMP4, we identified that our protocol can generate all major sensory neuron subtypes that are required for relaying sensation like pain, itch, heat and proprioception in the spinal cord. This analysis also identified functional features in each neuronal subtypes, confirming the bonafide status of the in vitro derived sensory neurons.
Project description:We report the genome-wide microRNA expression levels in pluripotent mESC and as mESC differentiate towards a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. microRNA-seq was performed to identify all microRNAs expressed in both ESCs and neuronal cells. In total, 534 expressed microRNAs we identified, of which 18 were up-regulated and 6 were down-regulated (fold change (FC) > -/+2.0 and p-value < 0.05) during Retinoic Acid-induced neuronal differentiation. The top up-regulated microRNAs identified were Mir10a, Mir615, Mir217 and Mir219a-2. The top down-regulated microRNAs identifed were Mir211, Mir292, Mir302a and Mir302c.
Project description:We report the genome-wide microRNA expression levels in pluripotent mESC and as mESC differentiate towards a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. microRNA-seq was performed to identify all microRNAs expressed in both ESCs and neuronal cells. In total, 534 expressed microRNAs we identified, of which 18 were up-regulated and 6 were down-regulated (fold change (FC) > -/+2.0 and p-value < 0.05) during Retinoic Acid-induced neuronal differentiation. The top up-regulated microRNAs identified were Mir10a, Mir615, Mir217 and Mir219a-2. The top down-regulated microRNAs identifed were Mir211, Mir292, Mir302a and Mir302c. Examination, identification and comparision of microRNA expression profliles in two cellular states.
Project description:We report the genome-wide binding patterns of nuclear FGFR1, RXR? and Nur77 in pluripotenet mESC and as mESC differentiate towared a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. We also report the genome-wide incorporation of histone varant H3.3 into chromatin specifically during Retinoic Acid-induced differentiation. This study presents nuclear FGFR1 as a global factor that controls genomic function by binding within the promoters of thousands of genes, both alone and in cooperation with RXR, Nur77 and histone H3.3, by targeting consensus DNA sequences of diverse transcription factor families. As such, it identifies a previously unknown, multifaceted form of control of major ontogenic pathways and gene networks targeted by the nuclear form of FGFR1. Examination of nuclear FGFR1, RXR?, and Nur77 binding sites in 2 celluar states. Examination of H3.3 incorporation in 1 cellular state.
Project description:We report the genome-wide binding patterns of nuclear FGFR1, RXRα and Nur77 in pluripotenet mESC and as mESC differentiate towared a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. We also report the genome-wide incorporation of histone varant H3.3 into chromatin specifically during Retinoic Acid-induced differentiation. This study presents nuclear FGFR1 as a global factor that controls genomic function by binding within the promoters of thousands of genes, both alone and in cooperation with RXR, Nur77 and histone H3.3, by targeting consensus DNA sequences of diverse transcription factor families. As such, it identifies a previously unknown, multifaceted form of control of major ontogenic pathways and gene networks targeted by the nuclear form of FGFR1.