Biology subjects

Li, H.-R.

Publications and source records attributed to Li, H.-R..

6 recordsLinked to original sources

bioRxiv2025

Deconstructing the common anteroposterior organisation of adult bilaterian guts

A through-gut is one of the major features of bilaterians. Comparative work among bilaterians has identified common molecular mechanisms during early gut patterning, but the primordial gut later often undergoes different degrees of reorganization in each lineage to form a fully differentiated adult gut with specializations along its anteroposterior (AP) axis. Yet, how the conserved embryonic gut AP pattern relates to the adult guts in diverse bilaterians after metamorphosis is still poorly understood. To unravel the molecular subdivisions of adult guts, we investigated the gut through transcriptomic analyses of five phylogenetically informative species, an annelid, a sea urchin, a hemichordate, a cephalochordate, and a vertebrate. We identified bipartite transcriptional programs defining the AP functional subdivisions. Patterning systems composed of Hox, Parahox, and, surprisingly, other transcription factors (TFs) known to be involved in gut formation in sea urchin larvae are maintained in these adult tissues. Using unbiased analyses, we identified five conserved TF modules corresponding to the AP compartments of the guts that are elaborated or shifted in different species. Our study inferred conserved and modified adult AP patterning modules along bilaterian guts enabling the reconstruction of ancestral bilaterian features with profound implications for the evolution of the bilaterian body plan.

developmental biology↗

bioRxiv2024

Unravelling the progression of the zebrafish primary body axis with reconstructed spatiotemporal transcriptomics

Elucidating the spatiotemporal dynamics of gene expression is essential for understanding complex physiological and pathological processes. Traditional technologies like in situ hybridization (ISH) and immunostaining have been restricted to analyzing expression patterns of a limited number of genes. Spatial transcriptomics (ST) has emerged as a robust alternative, enabling the investigation of spatial patterns of thousands of genes simultaneously. However, current ST methods are hindered by low read depths and limited gene detection capabilities. Here, we introduce Palette, a pipeline that infers detailed spatial gene expression patterns from bulk RNA-seq data, utilizing existing ST data as only reference. This method identifies more precise expression patterns by smoothing, imputing and adjusting gene expressions. We applied Palette to construct the Danio rerio SpatioTemporal Expression Profiles (DreSTEP) by integrating 53-slice serial bulk RNA-seq data from three developmental stages with existing ST references and 3D zebrafish embryo images. DreSTEP provides a comprehensive cartographic resource for examining gene expression and spatial cell-cell interactions within zebrafish embryos. Utilizing machine learning-based screening, we identified key morphogens and transcription factors (TFs) essential for anteroposterior (AP) axis development and characterized their dynamic distribution throughout embryogenesis. In addition, among these TFs, Hox family genes were found to be pivotal in AP axis refinement. Their expression was closely correlated with cellular AP identities, and hoxb genes may act as central regulators in this process.

developmental biology↗

bioRxiv2022

Cocaine addiction-like behaviors are associated with long-term changes in gene regulation, energy metabolism, and GABAergic inhibition within the amygdala

The amygdala processes positive and negative valence and contributes to the development of addiction, but the underlying cell type-specific gene regulatory programs are unknown. We generated an atlas of single nucleus gene expression and chromatin accessibility in the amygdala of outbred rats with low and high cocaine addiction-like behaviors following prolonged abstinence. Between rats with different addiction indexes, we identified thousands of cell type-specific differentially expressed genes enriched for energy metabolism-related pathways that are known to affect synaptic transmission and action potentials. Rats with high addiction-like behaviors showed enhanced GABAergic transmission in the amygdala, which, along with relapse-like behaviors, were reversed by inhibition of Glyoxalase 1, which metabolizes the GABAA receptor agonist methylglyoxal. Finally, we identified thousands of cell type-specific chromatin accessible sites and transcription factor (TF) motifs where accessibility was associated with addiction index, most notably at motifs for pioneer TFs in the Fox, Sox, helix-loop-helix, and AP1 families.

genomics↗

bioRxiv2021

Chronic adolescent exposure to cannabis in mice leads to long-term sex-biased changes in gene expression networks across brain regions

During adolescence, frequent and heavy cannabis use can lead to serious adverse health effects and cannabis use disorders (CUD). Rodent models of adolescent exposure to the main psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), mimic the behavioral alterations observed in adolescent users. However, the underlying molecular mechanisms remain largely unknown. Here, we treated female and male mice with high doses of THC during early adolescence and assessed their memory and social behaviors in late adolescence. We then profiled the transcriptome of five brain regions involved in cognitive and addiction-related processes. We applied gene coexpression network analysis and identified gene coexpression modules, termed cognitive modules, that simultaneously correlated with THC treatment and memory traits reduced by THC. The cognitive modules were related to endocannabinoid signaling in the female dorsal medial striatum, inflammation in the female ventral tegmental area, and synaptic transmission in the male nucleus accumbens. Moreover, cross-brain region module-module interaction networks uncovered intra- and inter-region molecular circuitries influenced by THC. Lastly, we identified key driver genes of gene networks associated with THC in mice and genetic susceptibility to CUD in humans. This analysis revealed a common regulatory mechanism linked to CUD vulnerability in the nucleus accumbens of females and males, which shared four key drivers (Hapln4, Kcnc1, Elav12, Zcchc12). These genes regulate transcriptional subnetworks implicated in addiction processes, synaptic transmission, brain development, and lipid metabolism. Our study provides novel insights into disease mechanisms regulated by adolescent exposure to THC in a sex- and brain region-specific manner.

neuroscience↗

bioRxiv2020

Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms

Identification of genomic mutations by molecular testing plays an important role in diagnosis, prognosis, and treatment of myeloid neoplasms. Next-generation sequencing (NGS) is an efficient method for simultaneous detection of clinically significant genomic mutations with high sensitivity. However, due to lack of standard NGS protocols, the application of NGS for hematologic malignancies into clinical settings remains limited. We report development and validation of a 48-gene NGS panel for molecular profiling of myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. A bioinformatics pipeline that was developed in-house was used to detect single nucleotide variations (SNVs), insertions/deletions (indels), and FLT3 internal tandem duplications (FLT3-ITD). An analytical validation study was performed on 184 unique specimens for variants with allele frequencies [≥]5%. Variants identified by the 48-gene panel were compared to those identified by a 35-gene hematologic neoplasms panel using an additional 137 unique specimens. The developed assay was applied to a large cohort (n=2,053) of patients with suspected myeloid neoplasms. Analytical validation yielded 99.6% sensitivity (95% CI: 98.9-99.9%) and 100% specificity (95% CI: 100%). Concordance of variants detected by the 2 tested panels was 100%. Among patients with suspected myeloid neoplasms (n=2,053), 54.5% patients harbored at least one clinically significant mutation: 77% in AML patients, 48% in MDS, and 45% in MPN. Together, these findings demonstrate that the assay can identify mutations associated with diagnosis, prognosis, and treatment options of myeloid neoplasms.

cancer biology↗

bioRxiv2018

Corilagin controls post-parasiticide schistosome egg-induced liver fibrosis by inhibiting Stat6 signalling pathway

This study aims to explore the effect of Corilagin (Cor) on post-parasiticide schistosome egg-induced hepatic fibrosis through the Stat6 signalling pathway in vitro and in vivo. Cellular and animal models were established and treated by Corilagin. The inhibitory effect of Corilagin was also confirmed in RAW264.7 cells in which Stat6 was overexpressed based on the GV367-Stat6-EGFP lentiviral vector system and in which Stat6 was knock-downed by gene specific siRNAs. As a result, Corilagin prevented increases in the protein level of Phospho-Stat6 (P-Stat6). Both the mRNA and protein levels of the downstream mediators SOCS1, KLF4, and PPAR{gamma}/{delta} were markedly suppressed after Corilagin treatment. Expression of ARG1 and FIZZ1/Retnla, Ym1, TGF-{beta} and PDGF in serum were also inhibited by Corilagin. The pathological changes, area of granulomas of liver sections, and degree of hepatic fibrosis were significantly alleviated in the Corilagin group. The areas of CD68- and CD206-positive cells stained by immunofluorescence were significantly decreased by Corilagin. In conclusion, Corilagin can suppress post-parasiticide schistosome egg-induced hepatic fibrosis by inhibiting the Stat6 signalling pathway and provide a new therapeutic strategy for schistosomiasis liver fibrosis.

pharmacology and toxicology↗