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. Author manuscript; available in PMC: 2017 Aug 19.
Published in final edited form as: Nat Med. 2016 Nov 21;23(1):49–59. doi: 10.1038/nm.4233

Figure 5.

Figure 5

ENS effects on the epithelium. (a–c) Heat maps of RNA-sequencing data from in vitro HIOs and HIOs+ENS. Curated list of digestive-tract development (a) and digestive function (b) genes revealed a differential regulation in HIOs+ENS, as compared to HIOs. A curated list of epithelial lineage markers, including enterocytes, goblet cells, enteroendocrine cells, Paneth cells and stem cell/transit-amplifying cells, is shown in c. Each lineage seemed to be affected by the presence of an ENS. (d) Double chromogenic staining with CDH1 and KI67 was performed to examine cell proliferation. HIOs+ENS (n = 4) showed increased proliferation, as compared to HIOs (n = 3), that was similar to human intestinal crypts (n = 3). Student's t test, two-tailed, unpaired. Data are presented as means ± s.e.m. (e) Imaging of enteroendocrine (SYN1, synapsin1; CHGA, chromogranin A) and neuronal cells (TUBB3) in HIOs+ENS (n = 6) showed no apparent interaction between neurons and enteroendocrine cells, as compared with human intestinal tissue (n = 4). Left, arrow indicates enteroendocrine cell neuropod in human ENS. Right, arrow indicates association of neurons and enteroendocrine cell in human ENS. Scale bars, 5 μm.