(A-H, M, N) Immunofluorescence analysis showed that S1pr2 block with 15 μM JTE013 in ALI cultures of 14.5 dpc embryonic pancreata for 6 d (14.5 dpc + 6 d) lead to the elimination of C-peptide+ endocrine cells (A, E, N) and Amylase+ acinar cells (B, F, N) and to a greatly expanded number of CK19+ duct-like cells (B, F, N). Markers of mature β cells (Pdx1) and acinar cells (Ptf1a) were also eliminated upon S1pr2 block (C, G, M), and cell survival was severely compromised, as shown by TUNEL immunofluorescence analysis (D, H). (I-L, M, N) Immunofluorescence and TUNEL analysis showed that addition of CTGF in the ALI cultures along with the S1pr2 block virtually eliminated cell death (L), without reversing the loss of C-peptide+ endocrine (I, N), Amylase+ acinar cells (J, N). A large number of CK19+ duct-like cells (J, N) and Pdx1+ cells (K, M) persisted. Scale bars, 80 μm (A, B, D-F, H-J, L) and 70 μm (C, G, K); ***p < 0.001; error bars show SD. For raw data please refer to the S1 Data file.