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SUMMARY Defects in somitogenesis result in vertebral malformations at birth known as spondylocostal dysostosis (SCDO). Somites are formed with a species-specific periodicity controlled by the “segmentation clock,” which comprises a group of oscillatory genes in the presomitic mesoderm. Here, we report that a segmentation clock model derived from human embryonic stem cells shows many hallmarks of the mammalian segmentation clock in vivo, including a dependence on the NOTCH and WNT signaling pathways. The gene expression oscillations are highly synchronized, displaying a periodicity specific to the human clock. Introduction of a point of mutation into HES7, a specific mutation previously associated with clinical SCDO, eliminated clock gene oscillations, successfully reproducing the defects in the segmentation clock. Thus, we provide a model for studying the previously inaccessible human segmentation clock to better understand the mechanisms contributing to congenital skeletal defects.

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Background: Irritable bowel syndrome (IBS) is a stress-sensitive disorder of brain-gut interactions associated with a higher prevalence of early adverse life events (EALs). However, it is incompletely understood how trauma severity or disclosure influence the risk of developing IBS or symptom severity.Aims: To determine whether: 1) IBS patients report a greater number of EALs compared with healthy controls (HCs), 2) trauma severity and first age of EAL increase the odds of IBS, 3) confiding in others reduces the odds of IBS, 4) the number, trauma severity, and first age of EAL are associated with symptom severity, 5) sex differences exist. Methods:In total, 197 IBS patients (72% women, mean age=30.28 years) and 165 HCs (59% women, mean age=30.77 years) completed the Childhood Traumatic Events Scale (CTES), measuring severity of EALs and degree of confiding in others. Regression analyses were used to predict IBS status from EALs and association between gastrointestinal (GI) symptoms and EALs.Results: A greater number of EALs [odds ratio (OR)=1.36, 95% confidence interval (CI), 1.14-1.62; p<0.001) and higher perceived trauma severity (OR=1.13, 95% CI, 1.08-1.19; p<0.001) were associated with increased odds of IBS. Confiding in others decreased the odds of having IBS (OR=0.83, 95% CI, 0.72-0.96; p=0.012). The first age of EAL was not predictive of IBS. No sex differences were found. Conclusions:Assessing the traumatic severity of EALs and amount of confiding in others is important as they can affect the risk of having IBS. Our findings emphasize early intervention to improve health outcomes in individuals with EALs.