1. Single Cell Analysis of Human Colonoids Exposed to Uranium-Bearing Dust
- Author
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Atanga, Roger, Appell, Lidia L., Thompson, Myranda N., Lauer, Fredine T., Brearley, Adrian, Campen, Matthew J., Castillo, Eliseo F., and In, Julie G.
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Physiological aspects ,Methods ,Health aspects ,Environmental aspects ,Colon -- Physiological aspects ,Uranium -- Health aspects -- Physiological aspects ,RNA sequencing -- Methods ,Epithelial cells -- Physiological aspects -- Environmental aspects ,Mine dust -- Health aspects -- Physiological aspects ,Colon (Anatomy) -- Physiological aspects ,Mine dusts -- Health aspects -- Physiological aspects - Abstract
Introduction Uranium mining in the United States arose in the 1940s, peaked in the 1970s, and subsided in the late 1980s, with extensive activity concentrated in Navajo, Puebloan, and other [...], BACKGROUND: Uranium exposure remains an important environmental legacy and physiological health concern, with hundreds of abandoned uranium mines located in the Southwestern United States largely impacting underserved indigenous communities. The negative effects of heavy metals on barrier permeability and inhibition of intestinal epithelial healing have been described; however, transcriptomic changes within the intestinal epithelial cells and impacts on lineage differentiation are largely unknown. OBJECTIVES: Herein, we sought to determine the molecular and cellular changes that occur in the colon in response to uranium bearing dust (UBD) exposure. METHODS: Human colonoids from three biologically distinct donors were acutely exposed to UBD then digested for single cell RNA sequencing to define the molecular changes that occur to specific identities of colonic epithelial cells. Validation in colonoids was assessed using morphological and imaging techniques. RESULTS: Human colonoids acutely exposed to UBD exhibited disrupted proliferation and hyperplastic differentiation of the secretory lineage cell, enteroendocrine cells (EEC). Single-cell RNA sequencing also showed more EEC subtypes present in UBD-exposed colonoids. DISCUSSION: These findings highlight the significance of crypt-based proliferative cells and secretory cell differentiation using human colonoids to model major colonic responses to uranium-bearing particulate dust exposure. https://doi.org/10.1289/EHP13855
- Published
- 2024
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