Biology subjects

Baek, S.-H.

Publications and source records attributed to Baek, S.-H..

3 recordsLinked to original sources

bioRxiv2024

Specialized Pericyte Subtypes in the Pulmonary Capillary

Pericytes (PCs) play crucial roles in capillary maturation, stability, and homeostasis. Impaired PC coverage and function are implicated in various diseases, including pulmonary arterial hypertension (PAH). Challenges investigating PC biology are largely due to the lack of a concise marker, resulting in difficulty distinguishing PCs from other mural cell populations, including smooth muscle cells (SMCs) and fibroblasts (FBs). Utilizing bioinformatic analysis and RNAscope, we identified HIG hypoxia-inducible domain family member 1B (Higd1b) as a unique and conserved gene marker for PCs and generated a novel knockin mouse line, Higd1b-CreERT2, which precisely labels PCs in the lung and heart. Human lung single-cell RNAseq suggested the presence of two HIGD1B+ PC subtypes with different functions. By lineage tracing pulmonary Higd1b+ cells exposed to hypoxia in vivo, we identified Type 1 PCs remained in the capillary network, while Type 2 PCs accumulated in the arterioles and coexpressed SMC markers and increased levels of Vimentin, associated with focal adhesion pathways. These results suggest that Type 1 PCs are specialized for supporting capillary EC homeostasis and quiescent, while Type 2 PCs are lineage active and located close to the border zone of the arterioles and capillaries, which may be motile and transition to SMC-like cells in hypoxia-induced pulmonary hypertension. The discovery of PC-type specialization in capillaries transforms our understanding of the structure, function and regulation of pulmonary capillary circulation and their contribution to vascular remodeling.

cell biology↗

bioRxiv2022

Detecting and dissecting signaling crosstalk via the multilayer network integration of signaling and regulatory interactions

The versatility of cellular response arises from the communication, or crosstalk, of signaling pathways in a complex network of signaling and transcriptional regulatory interactions. Understanding the various mechanisms underlying crosstalk on a global scale requires untargeted computational approaches. We present a network-based statistical approach, MuXTalk, that uses high-dimensional edges called multilinks to model the unique ways in which signaling and regulatory interactions can interface. We demonstrate that the signaling-regulatory interface is located primarily in the intermediary region between signaling pathways where crosstalk occurs, and that multilinks can differentiate between distinct signaling-transcriptional mechanisms. Using statistically over-represented multilinks as proxies of crosstalk, we predict crosstalk among 60 signaling pathways, expanding currently available crosstalk databases by more than five-fold. MuXTalk surpasses existing methods in terms of prediction performance, identifies additions to manual curation efforts, and pinpoints potential mediators of crosstalk for each prediction. Moreover, it accommodates the inherent context-dependence of crosstalk, allowing future applications to cell type- and disease-specific crosstalk.

systems biology↗

bioRxiv2020

Robust and sensitive detection of SARS-CoV-2 using PCR based methods

The World Health Organization (WHO) has declared the Coronavirus disease 2019 (COVID-19) as an international health emergency. Current diagnostic tests are based on the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method, the gold standard test that involves the amplification of viral RNA. However, the RT-qPCR assay has limitations in terms of sensitivity and quantification. In this study, we tested both qPCR and droplet digital PCR (ddPCR) to detect low amounts of viral RNA. The cycle threshold (CT) of viral RNA by RT-PCR significantly varied according to the sequence of primer and probe sets with in vitro transcript (IVT) RNA or viral RNA as templates, whereas the copy number of viral RNA by ddPCR was effectively quantified with IVT RNA, cultured viral RNA, and RNA from clinical samples. Furthermore, the clinical samples were assayed via both methods, and the sensitivity of the ddPCR was determined to be significantly higher than RT-qPCR. These findings suggest that ddPCR could be used as a highly sensitive and compatible diagnostic method for viral RNA detection.

microbiology↗