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Ruiqi Li

Publications and source records attributed to Ruiqi Li.

2 recordsLinked to original sources

Sharp cell type boundaries emerge from coordinated morphogen signaling.

Classic models of the French flag problem depict sharp cell type boundaries emerging from threshold responses to morphogen gradients. How discrete cell type boundaries arise from morphogen signals that vary continuously across developing tissues remains incompletely understood. We use hair follicle dermal condensate (DC) formation to study a sharp developmental transition in which proliferative progenitors undergo cell cycle exit concurrent with molecular differentiation. Using genetic and genomic approaches, we show that Wnt and Hedgehog signaling coordinate separable cellular events during DC commitment. Elevated Wnt signaling promotes cell cycle exit through reduced chromatin binding of the Hedgehog mediator GLI3, while Hedgehog signaling induces differentiation genes in a Wnt-dependent manner and simultaneously elevates Wnt activity. When these responses coincide, differentiation and cell cycle exit occur together, limiting the duration and abundance of intermediate states and producing a sharp boundary. When they do not, intermediate states persist and expand, producing a graded boundary. Thus, a sharp boundary can emerge from a continuous transition that is compressed in time and space.

Hedgehog

Microbial DNA analysis of paired blood-bronchoalveolar lavage fluid in post-HSCT patients with pneumonia implying application conditions of blood as a surrogate in pathogen detection.

BACKGROUND: Blood testing aids pneumonia diagnosis, but its effectiveness varies. Given the invasiveness of bronchoalveolar lavage fluid (BALF) sampling versus blood testing's simplicity, this study investigates when blood can reliably substitute for BALF in detecting microbial presence, especially for pathogens. RESULTS: Metagenomic sequencing was performed on paired BALF-blood samples from 21 post-HSCT immunocompromised (ICP) and 21 immunocompetent (ICT) patients. The ICP cohort was expanded to 62 for biomarker validation. Host responses were profiled via metatranscriptomics (30 BALF samples). Microbial alpha and beta diversity differed significantly between blood and BALF in ICP, but not ICT, patients. ICP patients' BALF contained a greater diversity and abundance of microbes. A higher proportion of microbial DNA sequences in ICP patients' blood was also present in their BALF, suggesting a potentially more permeable alveolar-capillary barrier. Related genes (e.g., NABA CORE MATRISOME, extracellular matrix organization, cell-cell adhesion) were downregulated. Upregulated pathways like VEGFA-VEGFR2 signaling and Rho GTPases suggested increased vascular permeability. In ICP patients, 419 microbial sequences in blood indicated their presence in the lower respiratory tract with > 70% certainty. CONCLUSION: Host immune status significantly influences blood-BALF microbial diversity differences. Shared blood-BALF microbial DNA sequences show potential for aiding pneumonia pathogen diagnosis, offering a novel biomarker identification approach.

Humans