Tuft cells are solitary chemosensory epithelial cells with microvilli at the top, which are found in hollow organs such as the gastrointestinal tract, pancreas, and lungs. Recently, an increasing number of studies have revealed the chemotactic abilities and immune function of the tuft cells, and numerous efforts have been devoted to uncovering the role of tuft cells in tumors. Notably, accumulating evidence has shown that the specific genes (POU2F3, DCLK1) expressed in tuft cells are involved in vital processes related with carcinogenesis and cancer development. However, the interaction between the tuft cells and cancer remains to be further elucidated. Here, based on an introduction of biological functions and specific markers of the tuft cells, we have summarized the functional roles and potential therapeutic implications of tuft cells in cancers, including pancreatic cancer, lung cancer, gastric cancer, colon cancer, and liver cancer, which is in the hope of inspiring the future research in validating tuft cells as novel strategies for cancer therapies.

The critical roles and therapeutic implications of tuft cells in cancer

Tuft cells are solitary chemosensory cells distributed mainly in hollow organs and detected in human and mouse pancreas precursor lesions of pancreatic cancer. Induced by inflammation and KRAS mutation, pancreatic acinar cell-derived tuft cells play a protective role in epithelium injury. The tumour suppression of tuft cells has been indicated in some studies. However, the function of tuft cells in pancreatic cancer remains unclear. In this review, we first introduce the definition of tuft cells and then review the relationship between tuft cells and pancreatic inflammation. In addition, we emphasized the role of tuft cells in the genesis and development of pancreatic cancers, especially the part of markers for tuft cell's doublecortin-like kinase 1 (DCLK1). Finally, we turn to the microscopic perspective and review the interactions between tuft cells and the microbiome in the pancreatic microenvironment. Overall, we describe the role of tuft cells in response to tissue damage and tumour progression in the pancreas. Nevertheless, the specific formation principle and the more detailed mechanism of action of tuft cells in the pancreas remain to be further explored. 

Advances in tuft cells, a chemosensory cell in sequential diseases of the pancreas.

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult to study organs, such as the pancreas. With the advent of these technologies and approaches, the field has grown, in just a few years, from profiling pancreas disease states to identifying molecular mechanisms of therapy resistance in pancreatic ductal adenocarcinoma, a particularly deadly cancer. Single-cell transcriptomics and related spatial approaches have identified previously undescribed epithelial and stromal cell types and states, how these populations change with disease progression, and potential mechanisms of action which will serve as the basis for designing new therapeutic strategies. Here, we review the recent literature on how single-cell transcriptomic approaches have changed our understanding of pancreas biology and disease progression.

/pdf/it-is-better-to-light-a-candle-than-to-curse-the-darkness-2d8rtyvn.pdf

It is better to light a candle than to curse the darkness: single-cell transcriptomics sheds new light on pancreas biology and disease

As the leading central immune organ, the thymus is where T cells differentiate and mature, and plays an essential regulatory role in the adaptive immune response. Tuft cells, as chemosensory cells, were first found in rat tracheal epithelial, later gradually confirmed to exist in various mucosal and non-mucosal tissues. Although tuft cells are epithelial-derived, because of their wide heterogeneity, they show functions similar to cholinergic and immune cells in addition to chemosensory ability. As newly discovered non-mucosal tuft cells, thymic tuft cells have been demonstrated to be involved in and play vital roles in immune responses such as antigen presentation, immune tolerance, and type 2 immunity. In addition to their unique functions in the thymus, thymic tuft cells have the characteristics of peripheral tuft cells, so they may also participate in the process of tumorigenesis and virus infection. Here, we review tuft cells' characteristics, distribution, and potential functions. More importantly, the potential role of thymic tuft cells in immune response, tumorigenesis, and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection was summarized and discussed. 

/pdf/thymic-tuft-cells-potential-regulators-of-non-mucosal-tissue-2cypyrn1.pdf

Thymic tuft cells: potential “regulators” of non-mucosal tissue development and immune response

Abstract We present an in-depth single cell atlas of in vitro multi-culture systems on human primary airway epithelium derived from normal and diseased lungs of 27 individual donors. Our large-scale single cell profiling identifies new cell states and differentiation trajectories of rare airway epithelial cell types in human distal lungs. By integrating single cell datasets of human lung tissues, we discover immune primed subsets enriched in lungs and organoids derived from patients with chronic respiratory disease. To demonstrate the full potential of our platform, we further illustrate transcriptomic responses to various respiratory virus infections in in vitro airway models. Our work constitutes a single-cell roadmap for the cellular and molecular characteristics of human primary lung cells in vitro and their relevance to human tissues in vivo . 

/pdf/a-single-cell-atlas-of-in-vitro-multi-systems-uncovers-in-38v26cl6.pdf

A single cell atlas of in vitro multi-systems uncovers in vivo lineage trajectory and cell state in the human lung

http://manuscript.elsevier.com/S095506742200028X/pdf/S095506742200028X.pdf

Taylor Culpepper

Papers

New insights into tuft cell formation: Implications for structure-function relationships.