Summary
To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and
in vivo
CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.
Rational control of the cooperativity of multiple noncovalent interactions often plays an important role in the design and construction of supramolecular self-assemblies and materials, especially in precision supramolecular engineering. However, it still remains a challenge to control the cooperativity of multiple noncovalent interactions through tuning the hydrophobic effect. In this work, we demonstrate that the binding cooperativity of cucurbit[8]uril(CB[8])-mediated homoternary complexes is strongly influenced by the amphiphilicity of guest molecule side groups on account of an interplay between both classical (entropy-driven) and nonclassical (enthalpy-driven) hydrophobic effects. To this end, we rationally designed and prepared a series of guest molecules bearing a benzyl group as the CB[8] homoternary binding motif with various hydrophilic and hydrophobic side groups for cooperative control. By gradually tuning side groups of the guest molecules from hydrophilic to hydrophobic, we are able to control the binding from positive to negative cooperativity. An advanced molecular recognition process and self-assembling system can be developed by adjusting the positive and negative cooperativity. The ability to regulate and control the binding cooperativity will enrich the field of supramolecular chemistry, and employing cooperativity-controlled multiple noncovalent interactions in precision supramolecular engineering is highly anticipated.
A new method for controllable supramolecular polymerization based on ABBA type monomer and cucurbit[8]uril monomer through host−guest interaction and photochemistry is reported. The molecular weight and polydispersity of supramolecular polymers can be well controlled by tuning the molar ratio of these host and guest monomers or by tuning the isomer ratio of azobenzene groups in the guest monomers upon the competitive irradiation of lights. This research provides a general methodology for the control of supramolecular polymerization and the structure of supramolecular polymers.
This
letter is aimed to develop a general strategy to fabricate
polypseudorotaxanes with controlled antibacterial activity based on
cationic polymers. As a proof of concept, the commercially available
antibacterial cationic polymer, ε-poly-l-lysine hydrochloride,
was chosen for the demonstration. Using host–guest chemistry,
cucurbit[7]uril (CB[7]), a water-soluble macrocyclic host, was employed
to bind with the positive charge and hydrophobic component on ε-poly-l-lysine hydrochlorides for antibacterial regulation. In this
way, by tuning the ratio of CB[7] to the cationic polymer, the antibacterial
polypseudorotaxane can be obtained, and the antibacterial efficiency
can be well tuned from 5% to 100%. This line of research will enrich
the field of cationic polymers and polypseudorotaxanes with important
functions on precise control over antibacterial activity.
We describe the preparation of cross-linked, polymeric organic nanoparticles (ONPs) with a single, covalently-linked DNA strand. The structure and functionalities of the ONPs are controlled by the synthesis of their parent linear block copolymers that provide monovalency, fluorescence and narrow size distribution. The ONP can also guide the deposition of chloraurate ions and gold nanoparticles (AuNPs) were prepared using the ONPs as templates. The DNA strand on AuNPs is shown to preserve its functions.
Multiplex imaging technologies are now routinely capable of measuring more than 40 antibody-labeled parameters in single cells. However, lateral spillage of signals in densely packed tissues presents an obstacle to the assignment of high-dimensional spatial features to individual cells for accurate cell-type annotation. We devised a method to correct for lateral spillage of cell surface markers between adjacent cells termed REinforcement Dynamic Spillover EliminAtion (REDSEA). The use of REDSEA decreased contaminating signals from neighboring cells. It improved the recovery of marker signals across both isotopic (i.e., Multiplexed Ion Beam Imaging) and immunofluorescent (i.e., Cyclic Immunofluorescence) multiplexed images resulting in a marked improvement in cell-type classification.
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