P097 Depletion of delta-like ligand 4 (Dll4) contributes to the alteration of secretory progenitor differentiation in SAMP1/YitFc mice with Crohn’s disease-like ileitis

S.N. Hong1, J.H. Song2, G. Seong1, S.M. Kong1, J.B. Shin1, K. Eun Ran1, C. Dong Kyung1, K. Young-Ho1

1Samsung Medical Center, Department of Gastroenterology, Seoul, Republic of Korea, 2Samsung Medical Center, Gastroenterology, Seoul, Republic of Korea


When the intestinal epithelium would be exposed to harmful substances, mucosal damage can be occurred and followed by epithelial restoration with regenerative epithelium derived from intestinal stem cells (ISCs). Crohn’s disease (CD) is characterised by chronic mucosal damage and ulceration predominantly involved in the ileum. Thus, we hypothesised that epithelial regeneration in CD might be impaired due to the dysfunction of ileal ISCs or its niche.


SAMP1/YitFcsI (SAMP1) mice are recombinant-inbred mice that spontaneously develop ileitis resembling human CD. Alterations in the crypt-villus structure, epithelial differentiation, organoid formation ability, and niche signalling pathways in the ileum of 10- to 14-week-old SAMP1 mice were analysed and compared with age-matched AKR mice.


In the ileum of SAMP1 mice, the depth of the crypts increased and the surface area of the villi decreased. While the number of ISCs in the ileal crypts did not differ between SAMP1 and AKR mice. The number of Paneth cells decreased and the number of transient amplifying cells increased. The organoid formation ability of the ileal crypts of SAMP1 mice decreased significantly compared with that of AKR mice. RNA-seq revealed a differential gene expression pattern of ileal crypts of SAMP1 mice compared with those of AKR mice. Among the ISCs and niche signalling, the expression of delta-like ligand 4 (Dll4) was significantly decreased and the expression of genes associated with Notch signalling tended to decrease in the ileal crypts of SAMP1 mice.


The characteristic ileitis in SAMP1 mice may be caused by impaired Dll4-Notch signalling.