TY - JOUR
T1 - Emergence and patterning dynamics of mouse-definitive endoderm
AU - Pour, Maayan
AU - Kumar, Abhishek Sampath
AU - Farag, Naama
AU - Bolondi, Adriano
AU - Kretzmer, Helene
AU - Walther, Maria
AU - Wittler, Lars
AU - Meissner, Alexander
AU - Nachman, Iftach
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/1/21
Y1 - 2022/1/21
N2 - The segregation of definitive endoderm (DE) from bipotent mesendoderm progenitors leads to the formation of two distinct germ layers. Dissecting DE commitment and onset has been challenging as it occurs within a narrow spatiotemporal window in the embryo. Here, we employ a dual Bra/Sox17 reporter cell line to study DE onset dynamics. We find Sox17 expression initiates in vivo in isolated cells within a temporally restricted window. In 2D and 3D in vitro models, DE cells emerge from mesendoderm progenitors at a temporally regular, but spatially stochastic pattern, which is subsequently arranged by self-sorting of Sox17 + cells. A subpopulation of Bra-high cells commits to a Sox17+ fate independent of external Wnt signal. Self-sorting coincides with upregulation of E-cadherin but is not necessary for DE differentiation or proliferation. Our in vivo and in vitro results highlight basic rules governing DE onset and patterning through the commonalities and differences between these systems.
AB - The segregation of definitive endoderm (DE) from bipotent mesendoderm progenitors leads to the formation of two distinct germ layers. Dissecting DE commitment and onset has been challenging as it occurs within a narrow spatiotemporal window in the embryo. Here, we employ a dual Bra/Sox17 reporter cell line to study DE onset dynamics. We find Sox17 expression initiates in vivo in isolated cells within a temporally restricted window. In 2D and 3D in vitro models, DE cells emerge from mesendoderm progenitors at a temporally regular, but spatially stochastic pattern, which is subsequently arranged by self-sorting of Sox17 + cells. A subpopulation of Bra-high cells commits to a Sox17+ fate independent of external Wnt signal. Self-sorting coincides with upregulation of E-cadherin but is not necessary for DE differentiation or proliferation. Our in vivo and in vitro results highlight basic rules governing DE onset and patterning through the commonalities and differences between these systems.
KW - Developmental genetics
KW - Embryology
UR - http://www.scopus.com/inward/record.url?scp=85121279305&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2021.103556
DO - 10.1016/j.isci.2021.103556
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C2 - 34988400
AN - SCOPUS:85121279305
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 1
M1 - 103556
ER -