Cellular origins and lineage relationships of the intestinal epithelium

Capdevila, Claudia; Trifas, Maria; Miller, Jonathan; Anderson, Troy; Sims, Peter A.; Yan, Kelley S.

doi:10.1152/ajpgi.00188.2021

Cited by 16 publications

(13 citation statements)

References 130 publications

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“…In a recent technical tour de force, Cagan and colleagues have found that the rate of somatic mutation, as measured in the intestine, scales with age. 23 This effect, no doubt protective of cancer, is unlikely to be the result of the decline in the Mitotic Fraction , as the cells in the intestine undergo a rate of mitosis vastly greater than the Mitotic Fraction in the body as a whole (although one point of view holds that the precursors of the crypt stem cells may have a more conventional level of mitotic activity 53,54 ). As the authors concluded, “The most notable finding of this study is the inverse scaling of somatic mutation rates with lifespan.…”

Section: Discussionmentioning

confidence: 99%

On How, and Why, and When, We Grow Old

Citti

Michaelson

2022

Preprint

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Growth and aging are fundamental features of animal life. The march from fertilization to oblivion comes in enormous variety: days and hundreds of cells for nematodes, decades and trillions of cells for humans. Since Verhulst (1838) proposed the Logistic Equation (exponential growth with countervailing linear decline in rate), biologists have searched for ever better density dependent growth equations, none which accurately capture the relationship between size and time for real animals. Furthermore, while growth and aging run in parallel, whether the relationship is causal has been unknown. Here we show, by examining growth and lifespan in units of numbers of cells, N, (Cellular Phylodynamics), that both processes are linked to the same reduction in the fraction of cells dividing, occurring by a simple expression, the Universal Mitotic Fraction Equation. Lifespan is correlated with an age when fewer than one-in a-thousand cells are dividing, quantifying the long-appreciated mechanism of aging, the failure of cells to be rejuvenated by dilution with new materials made, and DNA repaired, at mitosis. These observations provide practical mathematical expressions for comprehending, and managing, the challenges of growth and aging, for such tasks as improving the effectiveness of COVID-19 vaccination in the elderly.

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Section: Discussionmentioning

confidence: 99%

On How, and Why, and When, We Grow Old

Citti

Michaelson

2022

Preprint

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“…It also has some of the same problems as phenetics. Breaking up continuous variation can involve subjective decisions (e.g., Cembrowski and Menon, 2018 ; Sagar and Grün, 2020 ), and the identification of biologically meaningful clusters from the high dimensional data produced by expression of 20,000 or more genes ( Efroni, 2018 ; Quake, 2021 ) makes clustering more an art than a science ( Kobak and Berens, 2019 ; Capdevila et al, 2021 ). Indeed, Chari et al (2021) referred to single cell genomics as a “specious art” based on their finding that commonly used unsupervised clustering approaches for dimensionality reduction do a poor job of grouping adjacent cells in this complex parameter space.…”

Section: Phenetics and Cladisticsmentioning

confidence: 99%

Cell types as species: Exploring a metaphor

Doyle

2022

Front. Plant Sci.

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The concept of “cell type,” though fundamental to cell biology, is controversial. Cells have historically been classified into types based on morphology, physiology, or location. More recently, single cell transcriptomic studies have revealed fine-scale differences among cells with similar gross phenotypes. Transcriptomic snapshots of cells at various stages of differentiation, and of cells under different physiological conditions, have shown that in many cases variation is more continuous than discrete, raising questions about the relationship between cell type and cell state. Some researchers have rejected the notion of fixed types altogether. Throughout the history of discussions on cell type, cell biologists have compared the problem of defining cell type with the interminable and often contentious debate over the definition of arguably the most important concept in systematics and evolutionary biology, “species.” In the last decades, systematics, like cell biology, has been transformed by the increasing availability of molecular data, and the fine-grained resolution of genetic relationships have generated new ideas about how that variation should be classified. There are numerous parallels between the two fields that make exploration of the “cell types as species” metaphor timely. These parallels begin with philosophy, with discussion of both cell types and species as being either individuals, groups, or something in between (e.g., homeostatic property clusters). In each field there are various different types of lineages that form trees or networks that can (and in some cases do) provide criteria for grouping. Developing and refining models for evolutionary divergence of species and for cell type differentiation are parallel goals of the two fields. The goal of this essay is to highlight such parallels with the hope of inspiring biologists in both fields to look for new solutions to similar problems outside of their own field.

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“…Some cells in the intestine can sense chemical and mechanical stimuli. Previous studies have classified the intestinal epithelium components as intestinal stem cells, enterocytes, goblet cells, tuft cells, enteroendocrine cells (EECs), and Paneth cells [ 7 ]. Epithelial cells work together to create a semipermeable barrier and are responsible for digestion, absorption, and immunity [ 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Ion Channels in the Chemotransduction and Mechanotransduction in Digestive Function and Feeding Behavior

Zhu

Liu

et al. 2022

IJMS

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The gastrointestinal tract constantly communicates with the environment, receiving and processing a wide range of information. The contents of the gastrointestinal tract and the gastrointestinal tract generate mechanical and chemical signals, which are essential for regulating digestive function and feeding behavior. There are many receptors here that sense intestinal contents, including nutrients, microbes, hormones, and small molecule compounds. In signal transduction, ion channels are indispensable as an essential component that can generate intracellular ionic changes or electrical signals. Ion channels generate electrical activity in numerous neurons and, more importantly, alter the action of non-neurons simply and effectively, and also affect satiety, molecular secretion, intestinal secretion, and motility through mechanisms of peripheral sensation, signaling, and altered cellular function. In this review, we focus on the identity of ion channels in chemosensing and mechanosensing in the gastrointestinal tract.

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Cellular origins and lineage relationships of the intestinal epithelium

Cited by 16 publications

References 130 publications

On How, and Why, and When, We Grow Old

On How, and Why, and When, We Grow Old

Cell types as species: Exploring a metaphor

Role of Ion Channels in the Chemotransduction and Mechanotransduction in Digestive Function and Feeding Behavior

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