Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1210-1227
Number of pages18
JournalStem Cell Reports
Volume16
Issue number5
DOIs
StatePublished - May 11 2021

Keywords

  • NODAL
  • WNT
  • ectoderm
  • endoderm
  • epiblast
  • gastrulation
  • gastruloid
  • mesoderm
  • primordial germ cell
  • stem cell differentiation

Fingerprint

Dive into the research topics of 'Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids'. Together they form a unique fingerprint.

Cite this