PubMed · 8203014
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N A Woychik. 1994. Regulating the regulators.. https://doi.org/10.1016/0968-0004(94)90199-6
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MOTIVATION: Identifying regulatory elements in various chromosomal regions that influence gene expression is a fundamental challenge in epigenomics, with profound implications for understanding gene regulation and disease mechanisms. The advent of paired single-cell RNA sequencing and single-cell ATAC sequencing has created unprecedented opportunities to address this challenge by enabling simultaneous profiling of gene expression and chromatin accessibility at single-cell resolution. However, the inherent signals between them are weak due to the highly sparse and noisy nature of data. RESULTS: This article proposes single-cell meta-Path based Omics Embedding (scPOEM), a novel embedding method that jointly projects chromatin accessibility peaks and expressed genes into a shared low-dimensional space. By integrating the relationships among peak-peak, peak-gene, and gene-gene interactions, scPOEM assigns closer representations in the embedding space to related peak-gene pairs. Our experiments demonstrate that scPOEM generates stable representations of peaks and genes, outperforms existing methods in recovering biologically meaningful peak-gene regulatory relationships and enables new insights in subgroup and differential analysis of gene regulation. These results highlight its potential to uncover gene regulatory mechanisms and enhance the understanding of transcriptional regulation at single-cell resolution. AVAILABILITY AND IMPLEMENTATION: The source code of scPOEM is available at https://github.com/Houyt23/scPOEM. The datasets can be obtained from the 10× Genomics (https://www.10xgenomics.com/datasets/pbmc-from-a-healthy-donor-granulocytes-removed-through-cell-sorting-10-k-1-standard-1-0-0) and GEO database under access codes GSE194122 and GSE239916.
Trk receptors are a family of genes implicated in the survival, differentiation, and growth of certain neurons and tumors of the nervous system. A better understanding of the regulation of Trk receptors is relevant for developmental and oncological studies. Human neuroblastoma (NB) cell lines constitutively express low levels of TrkA mRNA, while TrkB mRNA is not readily detectable. Differentiation of NB cells is accompanied by a differential modulation of Trk expression in human NB cells. Nanomolar concentrations of RA induce a stable increase of TrkB mRNA. A transient induction of TrkA mRNA levels requires micromolar concentrations of RA. Induction of both TrkA and TrkB mRNA does not require new protein synthesis. However, RA-induced TrkB mRNA expression is transcriptionally regulated, while the transient RA-induced increase of TrkA mRNA is a consequence of extended mRNA stability. Interferon gamma (IFN-gamma) selectively increases TrkA mRNA without affecting TrkB mRNA levels. Similar to RA, IFN-gamma does not modify the transcriptional rate of TrkA mRNA, but rather increases TrkA mRNA stability. Thus, RA and IFN-gamma differentially regulate TrkA or TrkB expression in the same cell type by predominantly transcriptional (TrkB) or post transcriptional (TrkA) mechanisms. Such experiments indicate the complexity of Trk mRNA regulation and also indicate compounds that may affect neurotrophin responsiveness in developing neural cells.
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