Morphogenesis and regeneration share a conserved core transition cell state program that controls lung epithelial cell fate.

Transitional cell states are at the crossroads of crucial developmental and regenerative events, yet little is known about how these states emerge and influence outcomes. The alveolar and airway epithelia arise from distal lung multipotent progenitors, which undergo cell fate transitions to form these distinct compartments. The identification and impact of cell states in the developing lung are poorly understood.

Identification and Targeting of Regulators of SARS-CoV-2-Host Interactions in the Airway Epithelium.

Although the impact of SARS-CoV-2 in the lung has been extensively studied, the molecular regulators and targets of the host-cell programs hijacked by the virus in distinct human airway epithelial cell populations remain poorly understood. This is in part ascribed to the use of nonprimary cell systems, overreliance on single-cell gene expression profiling that does not ultimately reflect protein activity, and bias toward the downstream effects rather than their mechanistic determinants. Here we address these issues by network-based analysis of single cell transcriptomic profiles of pathophysiologically relevant human adult basal, ciliated and secretory cells to identify master regulator (MR) protein modules controlling their SARS-CoV-2-mediated reprogramming.

High-fidelity ATP imaging an isothermal cascade catalytic amplifier.

Artificial catalytic DNA circuits that can identify, transduce and amplify the biomolecule of interest have supplemented a powerful toolkit for visualizing various biomolecules in cancer cells. However, the non-specific response in normal tissues and the low abundance of analytes hamper their extensive biosensing and biomedicine applications. Herein, by combining tumor-responsive MnO nanoparticles with a specific stimuli-activated cascade DNA amplifier, we propose a multiply guaranteed and amplified ATP-sensing platform the successive cancer-selective probe exposure and stimulation procedures.

Airway basal cells show regionally distinct potential to undergo metaplastic differentiation.

Basal cells are multipotent stem cells of a variety of organs, including the respiratory tract, where they are major components of the airway epithelium. However, it remains unclear how diverse basal cells are and how distinct subpopulations respond to airway challenges. Using single cell RNA-sequencing and functional approaches, we report a significant and previously underappreciated degree of heterogeneity in the basal cell pool, leading to identification of six subpopulations in the adult murine trachea.

A Mitochondrial Oxidative Stress Amplifier to Overcome Hypoxia Resistance for Enhanced Photodynamic Therapy.

Hypoxia-induced resistance to tumor treatment restricts further development of photodynamic therapy. Instead of simple reoxygenation to relieve hypoxia in traditional therapeutic approaches, a mitochondria-targeted reactive oxygen species (ROS) amplifier is constructed to reverse hypoxia resistance and enhance tumor sensitivity to hypoxia-resistant photodynamic therapy. Mesoporous silica nanoparticles are modified with triphenylphosphine to enhance its blood circulation and endow it with mitochondria-targeted specificity.

A Cooperatively Activatable DNA Nanoprobe for Cancer Cell-Selective Imaging of ATP.

DNA-based nanoprobes have attracted extensive interest in the field of bioanalysis. Notably, engineered DNA nanoprobes that can respond to multiple pathological parameters are desirable to detect targets precisely. Here we design a split aptamer/DNAzyme (aptazyme)-based DNA probe for fluorescence detection of ATP and further develop a cooperatively activatable DNA nanoprobe for tumor-specific imaging of ATP .

Cascaded Amplifier Nanoreactor for Efficient Photodynamic Therapy.

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) to treat established diseases and has attracted growing attention in the field of cancer therapy. However, in a tumor microenvironment (TME), the inherent hypoxia and high level of antioxidants severely hamper the efficacy of ROS generation. Here, we describe a cascaded amplifier nanoreactor based on self-assembled nanofusiforms for persistent oxygenation to amplify ROS levels.

Distinct and sequential re-replication barriers ensure precise genome duplication.

Achieving complete and precise genome duplication requires that each genomic segment be replicated only once per cell division cycle. Protecting large eukaryotic genomes from re-replication requires an overlapping set of molecular mechanisms that prevent the first DNA replication step, the DNA loading of MCM helicase complexes to license replication origins, after S phase begins. Previous reports have defined many such origin licensing inhibition mechanisms, but the temporal relationships among them are not clear, particularly with respect to preventing re-replication in G2 and M phases.

Programming DNA Nanoassembly for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) has extraordinary promise for the treatment of many cancers. However, its clinical progress is impaired by the intrinsic hypoxic tumor microenvironment that limits PDT efficacy and the safety concern associated with biological specificity of photosensitizers or vehicles. Now it is demonstrated that rationally designed DNA nanosponges can load and delivery photosensitizer effectively, target tumor precisely, and relieve hypoxia-associated resistance remarkably to enhance the efficacy of PDT.

Cdt1 stabilizes kinetochore-microtubule attachments via an Aurora B kinase-dependent mechanism.

Robust kinetochore-microtubule (kMT) attachment is critical for accurate chromosome segregation. G2/M-specific depletion of human Cdt1 that localizes to kinetochores in an Ndc80 complex-dependent manner leads to abnormal kMT attachments and mitotic arrest. This indicates an independent mitotic role for Cdt1 in addition to its prototypic function in DNA replication origin licensing.

Nanog suppresses cell migration by downregulating thymosin β4 and Rnd3.

Nanog, Sox2, and Oct4 are key transcription factors critical for the pluripotency and self-renewal of embryonic stem (ES) cells. Their downregulations lead to differentiation, accompanied with changes in cell motility. Whether these factors impact cell motility directly, however, is not clear.

miR-129-3p controls cilia assembly by regulating CP110 and actin dynamics.

Ciliogenesis requires the removal of CP110 from the mother centriole; actin dynamics also influence ciliation, at least partly by affecting the centrosomal accumulation of ciliogenic membrane vesicles. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p, a microRNA conserved in vertebrates, controlled cilia biogenesis in cultured cells by concomitantly downregulating CP110 and repressing branched F-actin formation.

Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells.

Cdc42GAP promotes inactivation of Cdc42, a small GTPase whose activation at the leading edge by guanine nucleotide exchange factors is critical for cell migration. How Cdc42GAP is regulated to ensure proper levels of active Cdc42 is poorly understood. Here we show that Nudel, a cytoplasmic dynein regulator, competes with Cdc42 for binding Cdc42GAP.