Frontiers in cell and developmental biology
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Front Cell Dev Biol · Jan 2021
ReviewThe Application of Single-Cell RNA Sequencing in Mammalian Meiosis Studies.
Meiosis is a cellular division process that produces gametes for sexual reproduction. Disruption of complex events throughout meiosis, such as synapsis and homologous recombination, can lead to infertility and aneuploidy. To reveal the molecular mechanisms of these events, transcriptome studies of specific substages must be conducted. ⋯ Next, we summarized the scRNA-seq analysis methods and the meiotic marker genes from spermatocytes and oocytes. Specifically, we emphasized the different features of the two scRNA-seq protocols (Smart-seq2 and Drop-seq) in the context of meiosis studies and discussed their strengths and weaknesses in terms of different research purposes. Finally, we discussed the future applications of scRNA-seq in the meiosis field.
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Front Cell Dev Biol · Jan 2020
ReviewThe Potential Roles of RNA N6-Methyladenosine in Urological Tumors.
N6-methyladenosine (m6A) is regarded as the most abundant, prevalent and conserved internal mRNA modification in mammalian cells. M6A can be catalyzed by m6A methyltransferases METTL3, METTL14 and WTAP (writers), reverted by demethylases ALKBH5 and FTO (erasers), and recognized by m6A -binding proteins such as YTHDF1/2/3, IGF2BP1/2/3 and HNRNPA2B1 (readers). Emerging evidence suggests that m6A modification is significant for regulating many biological and cellular processes and participates in the pathological development of various diseases, including tumors. This article reviews recent studies on the biological function of m6A modification and the methylation modification of m6A in urological tumors.
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Front Cell Dev Biol · Jan 2020
A Novel Strategy to Enhance Microfracture Treatment With Stromal Cell-Derived Factor-1 in a Rat Model.
Microfracture is one of the most widely used techniques for the repair of articular cartilage. However, microfracture often results in filling of the chondral defect with fibrocartilage, which exhibits poor durability and sub-optimal mechanical properties. Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for mesenchymal stem cells (MSCs) and is expressed at high levels in bone marrow adjacent to developing cartilage during endochondral bone formation. Integrating SDF-1 into an implantable collagen scaffold may provide a chondro-conductive and chondro-inductive milieu via chemotaxis of MSCs and promotion of chondrogenic differentiation, facilitating more robust hyaline cartilage formation following microfracture. ⋯ In this study, we demonstrated a simple method for improving the quality of cartilage defect repair in a rat model of microfracture. We confirmed the chemotactic properties of SDF-1 on rat MSCs and found an optimized dosage range for chemotaxis between 10 and 100 ng/ml. Furthermore, we demonstrated a strategy to incorporate SDF-1 into gelatin-collagen I scaffolds in vivo at the site of an osteochondral defect. SDF-1-treated defects displayed robust hyaline cartilage resurfacing of the defect with minimal fibrous tissue, in contrast to the empty control group. The results of the in vitro and in vivo studies together suggest that SDF-1-mediated signaling may significantly improve the quality of cartilage regeneration in an osteochondral defect.
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Front Cell Dev Biol · Jan 2020
ReviewInsights on SARS-CoV-2 Molecular Interactions With the Renin-Angiotensin System.
The emergence of SARS-CoV-2/human/Wuhan/X1/2019, a virus belonging to the species Severe acute respiratory syndrome-related coronavirus, and the recognition of Coronavirus Disease 2019 (COVID-19) as a pandemic have highly increased the scientific research regarding the pathogenesis of COVID-19. The Renin Angiotensin System (RAS) seems to be involved in COVID-19 natural course, since studies suggest the membrane-bound Angiotensin-converting enzyme 2 (ACE2) works as SARS-CoV-2 cellular receptor. Besides the efforts of the scientific community to understand the virus' molecular interactions with human cells, few studies summarize what has been so far discovered about SARS-CoV-2 signaling mechanisms and its interactions with RAS molecules. ⋯ On the other hand, Ang-(1-7) promotes anti-inflammatory effects through its interactions with the Mas Receptor. These molecules might be possible therapeutic targets for treating COVID-19. Thus, the understanding of SARS-CoV-2 intracellular pathways and interactions with the RAS may clarify COVID-19 physiopathology and open perspectives for new treatments and strategies.
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Front Cell Dev Biol · Jan 2020
ReviewResistance Mechanisms of Anti-PD1/PDL1 Therapy in Solid Tumors.
In cancer-immunity cycle, the immune checkpoint PD1 and its ligand PDL1 act as accomplices to help tumors resist to immunity-induced apoptosis and promote tumor progression. Immunotherapy targeting PD1/PDL1 axis can effectively block its pro-tumor activity. Anti-PD1/PDL1 therapy has achieved great success in the past decade. ⋯ Some oncogenic signaling pathways also contribute to the primary resistance. Under the pressure applied by anti-PD1/PDL1 therapy, tumors experience immunoediting and preserve beneficial mutations, upregulate the compensatory inhibitory signaling and induce re-exhaustion of T cells, all of which may attenuate the durability of the therapy. Here we explore the underlying mechanisms in detail, review biomarkers that help identifying responders among patients and discuss the strategies that may relieve the anti-PD1/PDL1 resistance.