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. Author manuscript; available in PMC: 2019 Oct 4.
Published in final edited form as: Cell Stem Cell. 2018 Sep 20;23(4):516–529.e5. doi: 10.1016/j.stem.2018.08.009

Figure 1. Derivation of esophageal progenitor cells (EPCs) from human embryonic stem cells (hESCs) by inhibiting TGFβ and BMP signaling.

Figure 1.

(A) Noggin-mediated inhibition of BMP signaling in mouse esophageal progenitor cells. BMP signaling is active in the ventral but not dorsal foregut where Nog-lacZ is expressed at E10.5. Note Nog-lacZ expression in the tracheal mesenchyme at E11.5 and E12.5. (B-C) Sequential differentiation of the human ES cell line RUES2 into EPCs. Scale bar: 100 μm. (D) Increased expression of EPC proteins during RUES2 differentiation. Note SOX2 levels were reduced at day4 but increased at day6. The fold change (Y axis) was generated by normalizing the transcript levels to those of day 1 (D1) hESC. Human fetal esophagus (Hu-Fetal) was included as control. Data represent mean ± SEM (n = 3). (E) Expression of p63 and NKX2.1 in cultures treated in parallel with either Noggin/SB-431542 or other factors from day6 to day16. The transcript levels of p63 and NKX2.1 were represented by the fold change compared to SFD condition. Data represent mean ± SEM (n = 3). **p < 0.01, ***p < 0.001 by unpaired, two-tailed Student’s t test. (F) Ectopic WNT activation inhibits AFE commitment to EPCs. The GSK3 inhibitor CHIR99021 (0.5, 1 or 3 μM) was added to the culture from day6 to day16 along with Noggin (NOG) and SB431542 (SB). The expression of p63, AXIN2, PROX1, HNF6 and SOX2 was quantified by qPCR and reported as the fold change compared to NOG+SB. Data represent mean ± SEM (n = 3). *p < 0.05, **p < 0.01 by unpaired, two-tailed Student’s t test. Abbreviation: Eso, esophagus; Tra, trachea; NOG, Noggin; SB, SB431542; CFKBR=CHIR99021, FGF10, KGF, BMP4 and Retinoic acid; SFD, serum free medium. N.S., not significant. See also Figures S1-S4.