Biology subjects

Zhang, Y.-Y.

Publications and source records attributed to Zhang, Y.-Y..

5 recordsLinked to original sources

bioRxiv2021

ACKR3 induces the perturbation of rRNA biogenesis: a novel mechanism of colorectal tumorigenesis

Atypical chemokine receptor 3 (ACKR3), previously known as C-X-C chemokine receptor type 7 (CXCR7), has emerged as a key player in several biologic processes. Its atypical "intercepting receptor" signaling properties have established ACKR3 as the main regulator in pathophysiological processes in many diseases. However, much less is known the underlying mechanisms of ACKR3 in promoting tumorigenesis. We found, in both human and animal model, that activation of ACKR3 promotes colorectal tumorigenesis through the NOLC1-induced perturbations of rRNA biogenesis. As compared with adjacent non-neoplastic tissue, human colonic cancer tissues demonstrated higher expression of ACKR3, and high ACKR3 expression was associated with increased severity of colonic cancer. Villin-ACKR3 transgenic mice demonstrated the characteristics of ACKR3-induced colorectal cancer, showing the nuclear {beta}-arrestin-1-activated perturbation of rRNA biogenesis. Activation of ACKR3 induced nuclear translocation of {beta}-arrestin-1 ({beta}-arr1), leading to the interaction of {beta}-arr1 with nucleolar and coiled-body phosphoprotein 1 (NOLC1). As the highly phosphorylated protein in the nucleolus, NOLC1 further interacted with Fibrillarin, a highly conserved nucleolar methyltransferase responsible for ribosomal RNA methylation, leading to the increase of methylation in Histone H2A, resulting in the promotion of rRNA transcription of ribosome biogenesis. Conclusion: ACKR3 promotes colorectal tumorigenesis through the perturbation of rRNA biogenesis by nuclear {beta}-arr1-induced interaction of NOLC1 with Fibrillarin. HIGH LIGHTSO_LIACKR3 is an atypical G protein-coupled receptor (GPCR) C_LIO_LIACKR3 promotes colorectal tumorigenesis C_LIO_LIACKR3 induces nuclear translocation of {beta}-arr1 C_LIO_LINuclear {beta}-arr1 interacts with NOLC1 to activate Fibrillarin C_LIO_LIInteraction of NOLC1 to Fibrillarin leads to perturbation of rRNA biogenesis C_LI

cancer biology↗

bioRxiv2021

Viromes in Marine Ecosystems Reveal Remarkable Invertebrate RNA Virus Diversity

Ocean viromes remain poorly understood and little is known about the ecological factors driving aquatic RNA virus evolution. In this study, we used a meta-transcriptomic approach to characterize the viromes of 58 marine invertebrate species across three seas. This revealed the presence of 315 newly identified RNA viruses in nine viral families or orders (Durnavirales, Totiviridae, Bunyavirales, Hantaviridae, Picornavirales, Flaviviridae, Hepelivirales, Solemoviridae and Tombusviridae), with most of them are sufficiently divergent to the documented viruses. With special notice that we first time revealed an ocean virus rooting to mammalian hantaviruses. We also found evidence for possible host sharing and switch events during virus evolution. In sum, we demonstrated the hidden diversity of marine invertebrate RNA viruses.

microbiology↗

bioRxiv2021

Generation of human blastocyst-like structures from pluripotent stem cells

Human blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast, and primitive endoderm, all of which are essential for early development and organ formation1,2. However, due to ethical concerns and restricted access to human blastocysts, we lack a comprehensive understanding of early human embryogenesis. To bridge this knowledge gap, we need a reliable model system that recapitulates early stages of human embryogenesis. Here we report a [~]three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids also exhibited the developmental potential to undergo post-implantation morphogenesis in vitro to form structures with a cellular composition and transcriptome signature similar to human embryos that had been cultured in vitro for 8 or 10 days. In conclusion, human EPS-blastoids provide a new experimental platform for studying early developmental stages of the human embryo. HighlightsA method for generating human blastoids from EPS cells. Human blastoids resemble blastocysts in terms of morphology and cell lineage composition. Single-cell transcriptomic analyses reveal EPI, PE, and TE cell lineages in human blastoids. Human blastoids mimic in vitro the morphogenetic events of pre- and early post-implantation stages.

developmental biology↗

bioRxiv2020

Multiple infiltration and cross-species transmission of foamy viruses across Paleozoic to Cenozoic era

Foamy viruses (FVs) are complex retroviruses that can infect humans and other animals. In this study, by integrating transcriptomic and genomic data, we discovered 412 FVs from 6 lineages in amphibians, which significantly increased the known set of FVs in amphibians. Among these lineages, salamander FVs maintained a co-evolutionary pattern with their hosts that could be dated back to the Paleozoic era, while, on the contrary, frog FVs were much more likely acquired from cross-species (class level) transmission in the Cenozoic era. In addition, we found three distinct FV lineages had integrated into the genome of a salamander. Unexpectedly, we identified a potential exogenous form of FV circulated in caecilian, demonstrating the existence of exogenous form of FV besides mammals. Our discovery of rare phenomena in amphibian FVs has overturned our collective understanding of the macroevolution of the complex retrovirus. ImportanceFoamy viruses (FVs) represent, more so than other viruses, the best model of co-evolution between a virus and a host. This study represents so far, the largest investigation of amphibian FVs and revealed 412 FVs of 6 distinct lineages from three major orders of amphibians. Besides co-evolutionary pattern, cross-species and repeated infection were also observed during evolution of amphibian FVs. Remarkably, expressed FVs including a potential exogenous form were discovered, suggesting live FVs could be underestimated in nature. These findings revealed the multiple origin and complex evolution of amphibian FVs started from the Paleozoic era.

microbiology↗

bioRxiv2020

The genomic and transcriptomic foundations of viviparous seed development in mangroves

Vivipary in plants refers to a specific seed development and reproductive strategy where seeds minimize the dormancy stage and germinate while still attached to their maternal plants. It is one of the most unique adaptive genetic features used by many mangrove species where elongated hypocotyls aid in quick root emergence to anchor the seedling in coastal intertidal wetlands. The genetic mechanisms behind mangrove vivipary, however, remain elusive. Using comparative genomic and transcriptomic technologies to investigate viviparous mangroves and their close inland relatives, we found that a full array of gene expression profiles were altered, including key plant hormone metabolic pathways, high expression of embryonic signature genes, and reduced production of proanthocyanidins and storage proteins. Along with these changes, a major gene regulating seed dormancy, Delay of Germination-1 (DOG1), is entirely missing or defunct within the entire linage of the four genera with true viviparous characteristics. These results suggest a systemic level change is required to warrant the genetic program of mangrove vivipary. Understanding of the molecular processes of vivipary could benefit the design of pregerminated propagules for forestation in harsh environments or prevent precocious germination of grain crops pre- and post-harvest.

genomics↗