Biology subjects

Hsieh, Y.-P.

Publications and source records attributed to Hsieh, Y.-P..

3 recordsLinked to original sources

bioRxiv2026

Microfluidic low-input profiling reveals lncRNA roles in disease

Long noncoding RNAs (lncRNAs) regulate gene expression through binding to DNA, various RNAs, and proteins, playing potentially important but poorly understood roles in diseases. Existing approaches for profiling lncRNA-chromatin interactions at the genome scale require large quantities of input material (e.g., 100 million cells per assay). Applying these technologies to tissue samples has been challenging especially when examination of a specific cell type is desired. Here we demonstrate a low-input microfluidic technology based on Chromatin Isolation by RNA Purification (ChIRP) for mapping lncRNA-chromatin interactions using as few as 50,000 cells. We validate our technology, muChIRP-seq, on two lncRNAs of different sizes (GOMAFU and TERC) in human and mouse cell lines and in brain tissues. Furthermore, we profile neuronal nuclei from postmortem human brain tissues of schizophrenia and control subjects. Our profiling data reveal distinct roles and levels of involvement for the two lncRNAs in contribution to schizophrenia. Our multimodal integrative analysis suggests coordination between lncRNA binding and other epigenomic mechanisms such as histone modifications in schizophrenia pathogenesis. Our technology enables lncRNA studies in tissue samples and in a cell-type-specific fashion, unlocking new opportunities to screen and understand lncRNA involvement in diseases.

genomics↗

bioRxiv2021

Epigenomic and transcriptomic differences between low-grade and acute inflammation in LPS-induced murine immune cells

Chronic, low-grade inflammation has a widespread and significant impact on health, especially in Western society. While inflammation is beneficial for the removal of microbes, low-grade inflammation never resolves and can cause or worsen other diseases. The process by which low-grade inflammation occurs remains poorly understood. Here we exposed murine bone-marrow derived monocytes to chronic lipopolysaccharide (LPS) stimulation at low dose or high dose, as well as a PBS control. The cells were profiled for genome-wide H3K27ac modification and gene expression. The gene expression of TRAM-deficient and IRAK-M-deficient monocytes with LPS exposure was also analyzed. We discover that low-grade inflammation preferentially utilizes the TRAM/TRIF-dependent pathway of TLR4 signaling, and induces the expression of interferon response genes. In contrast, acute inflammation uniquely upregulates metabolic and proliferative pathways that also appear to be TRAM-dependent. The extensive differences in the epigenomic landscape between low-dose and high-dose conditions suggest the importance of epigenetic regulations in driving differential responses. Our data provide potential targets for future mechanistic or therapeutic studies.

immunology↗

bioRxiv2020

Cell-type-specific epigenomic variations associated with BRCA1 mutation in pre-cancer human breast tissues

BRCA1 germline mutation carriers are predisposed to breast cancers. Epigenomic regulations have been known to strongly interact with genetic variations and potentially mediate biochemical cascades involved in tumorigenesis. Due to the cell-type specificity of epigenomic features, profiling of individual cell types is critical for understanding the molecular events in various cellular compartments within complex breast tissue. Here we report cell-type-specific profiling of genome-wide histone modifications including H3K27ac and H3K4me3 in basal, luminal progenitor, mature luminal, and stromal cells extracted from pre-cancer BRCA1 mutation carriers and non-carriers, conducted using a low-input technology that we developed. We discover that basal and stromal cells present the most extensive epigenomic differences between mutation carriers (BRCA1mut/+) and non-carriers (BRCA1+/+) while luminal progenitor and mature luminal cells are relatively unchanged with the mutation. Furthermore, the epigenomic changes in basal cells due to BRCA1 mutation appear to facilitate their transformation into luminal progenitor cells. Our findings shed light on the pre-cancer epigenomic dynamics due to BRCA1 mutation and how they may contribute to eventual development of predominantly basal-like breast cancer.

genomics↗