Biology subjects

Cho, J. S.

Publications and source records attributed to Cho, J. S..

3 recordsLinked to original sources

bioRxiv2024

NRP1-expressing myeloid cells promote arteriogenesis in the ischemic limb

Peripheral arterial disease can cause limb threatening blood flow restriction, requiring amputation in up to a third of patients despite contemporary treatments. Stimulating new blood vessel growth in ischemic limbs using growth factors such as VEGF-A or supplying mixed cell populations via autologous transplantation has been investigated as a therapy for surgically intractable cases, but to date has proven ineffective in randomised controlled clinical studies. To identify more potent pro-arteriogenic cell populations, we have investigated VEGF-A responsive myeloid cell populations in a mouse model of severe hindlimb ischemia. We found that NRP1 ablation from monocytes and macrophages impaired arteriogenesis in the adductor muscle and flow recovery in the injured limb. Vice versa, the exogenous delivery of NRP1-expressing (but not NRP1-negative) macrophages enhanced arteriogenesis in the adductor and flow recovery in the ischemic limb in a VEGF signalling-dependent manner. Further, patient-derived NRP1-expressing monocytes promoted vascular morphogenesis ex vivo. As the levels of circulating NRP1-expressing monocytes were raised in patients with limb ischemia, the therapeutic delivery of autologous NRP1-expressing monocytes could be explored as a treatment for critical limb ischemia.

pathology↗

bioRxiv2022

Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis

Histone acetylation is a pivotal epigenetic modification that controls chromatin structure and regulates gene expression. It plays an essential role in modulating zygotic transcription and cell lineage specification of developing embryos. While the outcomes of many inductive signals have been described to require enzymatic activities of histone acetyltransferases and deacetylases (HDACs), the mechanisms by which HDACs confine the utilization of the zygotic genome remain to be elucidated. Here, we show that histone deacetylase 1 (Hdac1) progressively binds to the zygotic genome from mid blastula and onward. The recruitment of Hdac1 to the genome at blastula is instructed maternally. Cis-regulatory modules (CRMs) bound by Hdac1 possess epigenetic signatures underlying distinct functions. We highlight a dual function model of Hdac1 where Hdac1 not only represses gene expression by sustaining a histone hypoacetylation state on inactive chromatin, but also maintains gene expression through participating in dynamic histone acetylation-deacetylation cycles on active chromatin. As a result, Hdac1 maintains differential histone acetylation states of bound CRMs between different germ layers and reinforces the transcriptional program underlying cell lineage identities, both in time and space. Taken together, our study reveals a comprehensive role for Hdac1 during early vertebrate embryogenesis.

genomics↗

bioRxiv2020

Uncovering the mesendoderm gene regulatory network through multi-omic data integration

Mesendodermal specification is one of the earliest events in embryogenesis, where cells first acquire distinct identities. Cell differentiation is a highly regulated process that involves the function of numerous transcription factors (TFs) and signaling molecules, which can be described with gene regulatory networks (GRNs). Cell differentiation GRNs are difficult to build because existing mechanistic methods are low-throughput, and high-throughput methods tend to be non-mechanistic. Additionally, integrating highly dimensional data comprised of more than two data types is challenging. Here, we use linked self-organizing maps to combine ChIP-seq/ATAC-seq with temporal, spatial and perturbation RNA-seq data from Xenopus tropicalis mesendoderm development to build a high resolution genome scale mechanistic GRN. We recovered both known and previously unsuspected TF-DNA/TF-TF interactions and validated through reporter assays. Our analysis provides new insights into transcriptional regulation of early cell fate decisions and provides a general approach to building GRNs using highly-dimensional multi-omic data sets. HighlightsO_LIBuilt a generally applicable pipeline to creating GRNs using highly-dimensional multi-omic data sets C_LIO_LIPredicted new TF-DNA/TF-TF interactions during mesendoderm development C_LIO_LIGenerate the first genome scale GRN for vertebrate mesendoderm and expanded the core mesendodermal developmental network with high fidelity C_LIO_LIDeveloped a resource to visualize hundreds of RNA-seq and ChIP-seq data using 2D SOM metaclusters. C_LI

genomics↗