In the originally published version of the paper ''The structure of the human cell cycle,'' Stallaert et al. neglected to reference the research done by Gut et al. ( 2018), upon which the primary experimental approaches are based. The reference appears below and has been cited in the following sentence: ''Following time-lapse imaging, cells were fixed and then subjected to multiple rounds of immunofluorescence using iterative indirect immunofluorescence imaging (4i) (Gut et al., 2018) to obtain measurements of 48 core cell cycle effectors (Table S1) in a total of 8,850 individual cells.'' The authors apologize for the error.
Background and Aims: Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies in healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics from 3 humans covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon.
Methods: 12,590 single epithelial cells from three independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and capacity for response to extrinsic signals along the gut axis across different humans.
Results: Cells were assigned to 25 epithelial lineage clusters. Human intestinal stem cells (ISCs) are not specifically marked by many murine ISC markers. Lysozyme expression is not unique to Paneth cells (PCs), and PCs lack expression of expected niche-factors. BEST4 cells express NPY and show functional and maturational differences between SI and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell-junction, and nutrient absorption genes show unappreciated regional expression differences across lineages. Differential expression of receptors and drug targets across lineages reveals biological variation and potential for variegated responses.
Conclusions: Our study identifies novel lineage marker genes; covers regional differences; shows important differences between mouse and human gut epithelium; and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves data gaps in anatomical regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.
Pig IL-8 increased in an ex vivo model of pig-to-human lung xenotransplantation but is not detected in vivo, whereas human or NHP IL-8 is elevated to a similar degree in both models. Both pig and human IL-8 activate human neutrophils and increase their adhesion to pig aortic ECs, a process significantly inhibited by the addition of Reparixin to human neutrophils. This work implicates IL-8, whether of pig or human origin, as a possible factor mediating in lung xenograft inflammation and injury and supports the evaluation of therapeutic targeting of this pathway in the context of xenotransplantation.
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