Biology subjects

Zhuo, D.

Publications and source records attributed to Zhuo, D..

6 recordsLinked to original sources

bioRxiv2025

Angptl5 restricts primitive hematopoiesis by modulating retinoic acid signaling in zebrafish

Homeostasis is essential for hematopoiesis, and its dysregulation can lead to severe pathological conditions. Retinoic acid (RA) is a key regulator that exerts concentration-dependent effects on both embryonic and adult hematopoiesis. However, the mechanisms that modulate RA signaling in hematopoietic processes remain poorly understood. Using zebrafish as a model, we identified angiopoietin-like protein 5 (Angptl5) as a critical regulator of hematopoietic homeostasis. Loss of Angptl5 function resulted in myeloid hyperplasia in the anterior lateral plate mesoderm (ALPM) and anterior expansion of erythroid progenitors in the posterior lateral plate mesoderm (PLPM)-- phenotypes consistent with attenuated RA signaling. Molecular analyses confirmed impaired RA signaling in angptl5{Delta}10/{Delta}10 mutants, and exogenous RA supplementation fully rescued the hematopoietic defects. Mechanistically, we found that Angptl5 transcriptionally activates retinol dehydrogenase dhrs9 through its interaction with Integrin 6l{beta}5. Our findings establish Angptl5 as a novel and essential regulator of embryonic hematopoiesis and reveal a previously unrecognized mechanism controlling hematopoietic homeostasis. These insights position Angptl5 as a potential therapeutic target for hematological disorders.

developmental biology↗

bioRxiv2023

Widespread mermithid nematode parasitism of Cretaceous insects

Mermithid nematodes are obligate invertebrate parasites dating back to the Early Cretaceous. Their fossil record is sparse, especially before the Cenozoic, thus little is known about their early host associations. This study reports 16 new mermithids associated with their insect hosts from mid-Cretaceous Kachin amber, 12 of which include previously unknown hosts. These fossils indicate that mermithid parasitism of invertebrates was already widespread and played an important role in the mid-Cretaceous terrestrial ecosystem. Remarkably, three hosts (bristletails, barklice and perforissid planthoppers) were previously unknown to be parasitized by mermithids both past and present. Furthermore, our statistical analyses show that in contrast to their Cenozoic counterparts, Cretaceous nematodes including mermithids are more abundant in heterometabolous insect hosts. This result suggests that nematodes have not completely exploited the dominant Holometabola as their hosts until the Cenozoic. This study reveals what appears to be a vanished history of nematodes that parasitized Cretaceous insects.

evolutionary biology↗

bioRxiv2022

The First Insight into the Epigenetic Fusion Gene Landscape of Acute Myeloid Leukemia

Epigenetic fusion genes have been defined as the fusion genes produced via cis-splicing of read-through pre-mRNAs of two identical-strand neighbor genes and have been known for decades. However, they need to be adequately investigated. In this study, we analyze RNA-Seq data from 390 AML patients and identify 12,754 EFG isoforms encoded by 5,213 EFGs, one-sixth of all potential EFGs. We characterize 479 EFG isoforms whose recurrent frequencies range from 10% to 96.2% and show that most of them result from developmental interactions between recurrent inherited genetic and environmental abnormalities. Novel EFG isoforms generated during late developments reflect somatic genetic abnormalities and environmental stresses. These characteristics of EFG isoforms make it possible for clustering heatmap and counting for EFG isoforms to distinguish GTEx healthy individuals and AML patients. This study reveals that human genomes encode potential EFGs equal to the total number of human genes and pseudogenes. EFGs provide one of the most powerful and economical tools to monitor the earliest signals from somatic genetic and environmental abnormalities.

genomics↗

bioRxiv2022

The Hereditary and Epigenetic Fusion Gene Signatures of Multiple Myeloma

Fusion transcripts are thought to be somatic and associated with cancer. However, they have been observed in healthy tissues at high recurrent frequencies. We have used SCIF (SplicingCodes Identify Fusion Transcripts) to analyze RNA-Seq data from 727 multiple myeloma (MM) patients of the MMRF CoMMpass Study. MTG1-SCART1, SCART1-CYP2E1, and TPM4-KLF2 have been detected in 96.1%, 95.7%, and 92.2% of 727 MM patients and formed fusion gene signatures. MTG1-SCART1 and SCART1-CYP2E1 are read-through from the same locus and the two most recurrent epigenetic fusion genes (EFGs) out of 187 EFGs detected in [≥]10% of 727 MM patients. TPM4-KLF2 fusion gene, which was initially thought to be somatic, has been shown by a monozygotic twin genetic model to be a hereditary fusion gene (HFG) and the dominant genetic factor associated with MM. This work provides the first line of evidence that HFGs are the genetic factors and EFGs reflect the consequences between genetics and environments during development.

cancer biology↗

bioRxiv2022

Hereditary Fusion Genes Are Associated with the Inheritance of Acute Myeloid Leukemia

Fusion genes are thought to be somatic and cause cancer, including acute myeloid leukemia (AML). Validating highly-recurrent fusion genes in healthy samples compelled us to systematically study hereditary fusion genes (HFGs). Here, we used curated HFGs to analyze AML fusion genes, and we identified 243 HFGs associated with AML inheritance from 926 potential HFGs. Many HFGs were one-to-many and many-to-one fusions that augmented signals from environmental and genomic alterations and seemed to support the "two-hit" hypothesis. The most highly-recurrent HFGs were also observed in multiple myeloma and monozygotic twin datasets, suggesting that AML is a complex genetic disease. HFGs, as cancer genetic biomarkers, are the most basic foundations for future genetic and genomic studies.

genetics↗

bioRxiv2022

The first glimpse of Homo sapiens hereditary fusion genes

Family-inherited fusion genes have been known to be associated with human disease for decades. However, only a small number of them have been discovered so far. In this report, monozygotic (MZ) twins are used as a genetic model to investigate hereditary fusion genes (HFG). We have analyzed RNA-Seq from 37 MZ twins and discovered 1,180 HFGs, the maximum of which is 608 per haploid genome. Eight HFGs associated with MZ twin inheritance range from 52.7% to 67.6%, some of which are previously-studied cancer fusion genes and indicate hereditary cancer genes. These data suggest that HFGs are major genetic factors for human diseases and complex traits. This study gives us the first glimpse of human HFGs and lays theoretical and technological foundations for future genetic and medical studies.

genomics↗