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To construct a comprehensive, tissue-scale map of the developing human small intestine, we leveraged single-cell RNA-sequencing data to build a custom Xenium spatial transcriptomics gene panel covering the diversity of cell types in the human intestine. Analysis was focused on the developing mesenchyme populations (also referred to as fibroblasts or stroma) given the lack of spatiotemporal information about these cell populations. We defined 5 broad mesenchymal populations occupying discrete anatomical locations within the lamina propria and submucosa \u2013 the subepithelial cells (SEC), lamina propria fibroblasts (LPF), submucosal fibroblasts (SMF), smooth muscle cells (SMC), and\n                  <jats:italic>CXCL13<\/jats:italic>\n                  + fibroblasts. Our data reveal dynamic spatial remodeling of fibroblast communities during development and establish molecular markers to distinguish these populations. We leverage this high-resolution atlas to benchmark pluripotent stem cell-derived human intestinal organoids and to demonstrate how this foundational resource can be used to dissect intestinal stromal signaling in a spatial manner, with broad implications for modeling development, regeneration, and disease.\n                <\/jats:p>\n                <jats:sec id=\"s24\">\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"665939v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                  <jats:sec id=\"s24a\">\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>A spatial atlas of fibroblast heterogeneity in the human intestine<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Populations include subepithelial, submucosal, lamina propria, and\n                          <jats:italic>CXCL13<\/jats:italic>\n                          + fibroblasts\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Fibroblast position in the developing intestine is maintained into adulthood<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Organoids largely recreate the spatial organization of the human intestine<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                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