Chapter 4 is focused on an in-depth analysis of epithelial and neuronal lineage composition and developmental relationships across different intestinal regions and life stages. This analysis reveals similarities in epithelial cell changes during development and regeneration. In addition, these cell type profiles and cell networks are compared and contrasted with cells found in the children diagnosed with chronic inflammation of the small intestines or Crohn’s disease. This chapter outlines the single-cell profiles of human embryonic and early fetal gut tissue and explores the interactions between epithelial and mesenchymal cells. Chapter 3 focuses on deciphering the key cell players in the process of human villus formation. Chapter 2 outlines the materials and methods used for the generation and analysis of single-cell and spatial data that will be discussed in the following results chapters. As an intestinal surface area, innervation and immunity are established during in utero development, this chapter will also outline the principles of relevant developmental events, namely villus formation, enteric nervous system development, and lymphoid structure formation. epithelium, enteric neurons, stromal and immune cells) required for the proper intestinal function, will be summarized. Following an overview of single-cell technologies, the intestinal spatial architecture, as well as key cell types (e.g. Chapter 1 introduces the advances in single-cell genomic approaches within the last decade and contrasts them with previous technologies used for cataloguing cells. Importantly, we use this data to gain new insights into intestinal cell organisation and function during in utero development, homeostasis, and in rare and complex diseases. The work presented in this thesis is focused on building a reference of human intestinal cell types using novel genomic approaches including single-cell RNA sequencing (scRNA- seq) and spatial transcriptomics. ![]() Nonetheless, a holistic view of intestinal cell diversity across distinct intestinal regions (space) and multiple life stages (time) is still lacking. ![]() Recent advances in high-throughput profiling of cells using transcriptomic approaches have vastly expanded the catalogue of cells that are found across the human body. Cells of the human intestinal tract undergo dynamic changes from development to adulthood and in response to environmental stimuli.
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