Towards precision medicine: Omics approach for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic had a devastating impact on human society. Beginning with genome surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of omics technologies brought a clearer understanding of the complex SARS-CoV-2 and COVID-19. Here, we reviewed how omics, including genomics, proteomics, single-cell multi-omics, and clinical phenomics, play roles in answering biological and clinical questions about COVID-19. Large-scale sequencing and advanced analysis methods facilitate COVID-19 discovery from virus evolution and severity risk prediction to potential treatment identification. Omics would indicate precise and globalized prevention and medicine for the COVID-19 pandemic under the utilization of big data capability and phenotypes refinement. Furthermore, decoding the evolution rule of SARS-CoV-2 by deep learning models is promising to forecast new variants and achieve more precise data to predict future pandemics and prevent them on time.

A Decade of GigaScience: Women in Science: Past, Present, and Future.

Over the last decade, women have made decisive advances in increasing equality in science, technology, engineering, and medicine (STEM), but they still do not rival that of men. Many mechanisms to reduce gender discrimination have been addressed; however, little to nothing has been done to tackle the differences in the amount of time women spend on responsibilities at home. This has never been more apparent than during the COVID-19 pandemic. After a decade of advances promoting women, the last two years have seen these advances halted, and the long-term implications for women in STEM will be substantial. Moving forward, career advancement and funding mechanisms need to be adjusted to not just help women catch up, but to become a permanent support mechanism for women in the workplace. The higher amount of responsibilities at home and lack of support for women is not reserved for times of international upheaval: it has just become more apparent.

Single-cell RNA sequencing technologies and applications: A brief overview.

Single-cell RNA sequencing (scRNA-seq) technology has become the state-of-the-art approach for unravelling the heterogeneity and complexity of RNA transcripts within individual cells, as well as revealing the composition of different cell types and functions within highly organized tissues/organs/organisms. Since its first discovery in 2009, studies based on scRNA-seq provide massive information across different fields making exciting new discoveries in better understanding the composition and interaction of cells within humans, model animals and plants. In this review, we provide a concise overview about the scRNA-seq technology, experimental and computational procedures for transforming the biological and molecular processes into computational and statistical data. We also provide an explanation of the key technological steps in implementing the technology. We highlight a few examples on how scRNA-seq can provide unique information for better understanding health and diseases. One important application of the scRNA-seq technology is to build a better and high-resolution catalogue of cells in all living organism, commonly known as atlas, which is key resource to better understand and provide a solution in treating diseases. While great promises have been demonstrated with the technology in all areas, we further highlight a few remaining challenges to be overcome and its great potentials in transforming current protocols in disease diagnosis and treatment.

A Brief Overview of Global Trends in MSC-Based Cell Therapy.

Human mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are important adult stem cells for regenerative medicine, largely due to their regenerative characteristics such as self-renewal, secretion of trophic factors, and the capability of inducing mesenchymal cell lineages. MSCs also possess homing and trophic properties modulating immune system, influencing microenvironment around damaged tissues and enhancing tissue repair, thus offering a broad perspective in cell-based therapies. Therefore, it is not surprising that MSCs have been the broadly used adult stem cells in clinical trials. To gain better insights into the current applications of MSCs in clinical applications, we perform a comprehensive review of reported data of MSCs clinical trials conducted globally. We summarize the biological effects and mechanisms of action of MSCs, elucidating recent clinical trials phases and findings, highlighting therapeutic effects of MSCs in several representative diseases, including neurological, musculoskeletal diseases and most recent Coronavirus infectious disease. Finally, we also highlight the challenges faced by many clinical trials and propose potential solutions to streamline the use of MSCs in routine clinical applications and regenerative medicine.

Composition and Dynamics of H1N1 and H7N9 Influenza A Virus Quasispecies in a Co-infected Patient Analyzed by Single Molecule Sequencing Technology.

A human co-infected with H1N1 and H7N9 subtypes influenza A virus (IAV) causes a complex infectious disease. The identification of molecular-level variations in composition and dynamics of IAV quasispecies will help to understand the pathogenesis and provide guidance for precision medicine treatment. In this study, using single-molecule real-time sequencing (SMRT) technology, we successfully acquired full-length IAV genomic sequences and quantified their genotypes abundance in serial samples from an 81-year-old male co-infected with H1N1 and H7N9 subtypes IAV. A total of 26 high diversity nucleotide loci was detected, in which the A-G base transversion was the most abundant substitution type (67 and 64%, in H1N1 and H7N9, respectively). Seven significant amino acid variations were detected, such as NA:H275Y and HA: R222K in H1N1 as well as PB2:E627K and NA: K432E in H7N9, which are related to viral drug-resistance or mammalian adaptation. Furtherly, we retrieved 25 H1N1 and 22 H7N9 genomic segment haplotypes from the eight samples based on combining high-diversity nucleotide loci, which provided a more concise overview of viral quasispecies composition and dynamics. Our approach promotes the popularization of viral quasispecies analysis in a complex infectious disease, which will boost the understanding of viral infections, pathogenesis, evolution, and precision medicine.

The Dynamic Changes of Transcription Factors During the Development Processes of Human Biparental and Uniparental Embryos.

Previous studies have revealed that transcription factors (TFs) play important roles in biparental (BI) early human embryogenesis. However, the contribution of TFs during early uniparental embryo development is still largely unknown. Here we systematically studied the expression profiles of transcription factors in early embryonic development and revealed the dynamic changes of TFs in human biparental and uniparental embryogenesis by single-cell RNA sequencing (scRNA-seq). In general, the TF expression model of uniparental embryos showed a high degree of conformity with biparental embryos. The detailed network analysis of three different types of embryos identified that 10 out of 17 hub TFs were shared or specifically owned, such as ZNF480, ZNF581, PHB, and POU5F1, were four shared TFs, ZFN534, GTF3A, ZNF771, TEAD4, and LIN28A, were androgenic (AG) specific TFs, and ZFP42 was the only one parthenogenetic (PG) specific TF. All the four shared TFs were validated using human embryonic stem cell (hESC) differentiation experiments; most of their target genes are responsible for stem cell maintenance and differentiation. We also found that Zf-C2H2, HMG, and MYB were three dominant transcription factor families that appeared in early embryogenesis. Altogether, our work provides a comprehensive regulatory framework and better understanding of TF function in human biparental and uniparental embryogenesis.

Direct observation of cell cycle progression in living mouse embryonic stem cells on an extracellular matrix of E-cadherin.

Self-renewal and differentiation of embryonic stem cells are tightly coordinated with cell-cycle progression and reconstructions. However, technical approach to directly visualize single embryonic stem cells still remains challenging. Here we combined two independent systems by using artificially constructed extracellular matrix that maintains embryonic stem cells in single level with cell cycle visualization reporters to directly observe cell cycle progression. Using Fucci (fluorescent ubiquitination-based cell cycle indicator) technology and computer-assisted fluorescence microscopy we were able to visualize cell cycle progression of mouse embryonic stem cells prepared from Fucci2 knock-in mice (mES/Fucci2). Imaged mES/Fucci2 cells were plated on coverslips coated with recombinant E-cadherin-IgG Fc (E-cad-Fc). This artificial extracellular matrix effectively increases adherence of cultured cells to coverslips, which is advantageous for fluorescence imaging. mES/Fucci2 cells on the E-cad-Fc maintained the typical cell cycle of mES cells with truncated G1 phase and pluripotency. During time-lapse imaging, we were able to track these cells with dendritic-like cell morphology and many pseudopodial protrusions. By contrast, the cell cycle progression of mES/Fucci2 cells on mouse embryonic fibroblasts (MEFs) was not observable due to their compact aggregation. Cell cycle duration of mES/Fucci2 cells on the E-cad-Fc was 16 h. Thus, the unique properties of our immunocytochemical analysis have revealed that decline of pluripotency of the Fucci2 mES cells on the E-cad-Fc was coordinated with their differentiation.