Reconstructing human pancreatic differentiation by mapping specific cell populations during development

TY - JOUR

T1 - Reconstructing human pancreatic differentiation by mapping specific cell populations during development

AU - Ramond, Cyrille

AU - Glaser, Nicolas

AU - Berthault, Claire

AU - Ameri, Jacqueline

AU - Kirkegaard, Jeannette Schlichting

AU - Hansson, Mattias

AU - Honoré, Christian

AU - Semb, Tor Henrik

AU - Scharfmann, Raphaël

PY - 2017

Y1 - 2017

N2 - Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate into the acinar, ductal or endocrine lineages. Development towards the acinar lineage is paralleled by an increase in GP2 expression. Conversely, a subset of the GP2+population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, a marker of endocrine differentiation. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.

AB - Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate into the acinar, ductal or endocrine lineages. Development towards the acinar lineage is paralleled by an increase in GP2 expression. Conversely, a subset of the GP2+population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, a marker of endocrine differentiation. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.

U2 - 10.7554/eLife.27564

DO - 10.7554/eLife.27564

M3 - Journal article

C2 - 28731406

AN - SCOPUS:85026906029

SN - 2050-084X

VL - 6

JO - eLife

JF - eLife

M1 - e27564

ER -