@article{29c8da33cf384917ad5ef30a1496b7fe,
title = "Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids",
abstract = "Human embryonic stem cells cultured in 2D micropatterns with BMP4 differentiate into a radial arrangement of germ layers and extraembryonic cells. Single-cell transcriptomes demonstrate generation of cell types transcriptionally similar to their in vivo counterparts in Carnegie stage 7 human gastrula. Time-course analyses indicate sequential differentiation, where the epiblast arises by 12 h between the prospective ectoderm in the center and the cells initiating differentiation toward extraembryonic fates at the edge. Extraembryonic and mesendoderm precursors arise from the epiblast by 24 h, while nascent mesoderm, endoderm, and primordial germ cell-like cells form by 44 h. Dynamic changes in transcripts encoding signaling components support a BMP, WNT, and Nodal hierarchy underlying germ-layer specification conserved across mammals, and FGF and HIPPO pathways being active throughout differentiation. This work also provides a resource for mining genes and pathways expressed in a stereotyped 2D gastruloid model, common with other species or unique to human gastrulation.",
keywords = "NODAL, WNT, ectoderm, endoderm, epiblast, gastrulation, gastruloid, mesoderm, primordial germ cell, stem cell differentiation",
author = "Minn, {Kyaw Thu} and Sabine Dietmann and Waye, {Sarah E.} and Morris, {Samantha A.} and Lilianna Solnica-Krezel",
note = "Funding Information: We thank Sandra Lam (Washington University School of Medicine in St. Louis) and Steven C. George (University of California in Davis) for their guidance and assistance in fabricating polydimethylsiloxane stamps. We thank Yuheng Fu and Chuner Guo (Washington University School of Medicine in St. Louis) for constructing parts of the data curation libraries. We thank Drs. Blerta Stringa and Florence Marlow for comments on the manuscript. This study was funded by Washington University School of Medicine in St. Louis, and a grant from the Children's Discovery Institute, St. Louis to L.S.K. and a Vallee Scholar Award, an Allen Distinguished Investigator Award (through the Paul G. Allen Frontiers Group), a Sloan Research Fellowship, and a New York Stem Cell Foundation Robertson Investigator award to S.A.M. Funding Information: We thank Sandra Lam (Washington University School of Medicine in St. Louis) and Steven C. George (University of California in Davis) for their guidance and assistance in fabricating polydimethylsiloxane stamps. We thank Yuheng Fu and Chuner Guo (Washington University School of Medicine in St. Louis) for constructing parts of the data curation libraries. We thank Drs. Blerta Stringa and Florence Marlow for comments on the manuscript. This study was funded by Washington University School of Medicine in St. Louis, and a grant from the Children's Discovery Institute , St. Louis to L.S.K., and a Vallee Scholar Award, an Allen Distinguished Investigator Award (through the Paul G. Allen Frontiers Group), a Sloan Research Fellowship, and a New York Stem Cell Foundation Robertson Investigator award to S.A.M. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = may,
day = "11",
doi = "10.1016/j.stemcr.2021.03.031",
language = "English",
volume = "16",
pages = "1210--1227",
journal = "Stem Cell Reports",
issn = "2213-6711",
number = "5",
}