Conversion of mouse ESCs to epiblast state enhances paraxial mesoderm
differentiation. (A) Schematic depiction of differentiation conditons. Note day
1 conditions for comparing delayed (2i), direct (FC), and epiblast (FA)
transitions into mesoderm. (B) Representative images of reporter expression on
day 3 of differentiation showing robust Tbx6 reporter
expression and spreading of T+ cells following
epiblast (FA) transition. T+ cells remained
clustered following direct mesoderm induction (FC), with limited Tbx6 reporter
expression. The persistence of numerous mounded, reporter-negative colonies
occurred with the 2i and FC transitions (white arrows), which were absent from
epiblast-transitioned cultures. (C) Day 3 FACS analysis shows epiblast
transition (FA) followed by two days of mesoderm differentiation generated
considerably more Tbx6+ cells compared to just two
(2i) or three (FC) days of mesoderm differentiation, with control stem cells
shown for comparison. (D) Day 3 gene expression indicated elevated levels of
early mesoderm genes T, Wnt3a, and Fgf8 and
substantial increases in the paraxial markers Tbx6 and
Msgn with FA transition compared to 2i or FC, which also
retained expression Sox2. Data shown as mean ± SEM (n =
3, *p < .05, where * denotes the comparison of FA
treatment to both 2i and FC).