Rapid and robust directed differentiation of mouse epiblast stem cells into definitive endoderm and forebrain organoids Journal Article


Authors: Medina-Cano, D.; Corrigan, E. K.; Glenn, R. A.; Islam, M. T.; Lin, Y.; Kim, J.; Cho, H.; Vierbuchen, T.
Article Title: Rapid and robust directed differentiation of mouse epiblast stem cells into definitive endoderm and forebrain organoids
Abstract: Directed differentiation of pluripotent stem cells (PSCs) is a powerful model system for deconstructing embryonic development. Although mice are the most advanced mammalian model system for genetic studies of embryonic development, state-of-the-art protocols for directed differentiation of mouse PSCs into defined lineages require additional steps and generates target cell types with lower purity than analogous protocols for human PSCs, limiting their application as models for mechanistic studies of development. Here, we examine the potential of mouse epiblast stem cells cultured in media containing Wnt pathway inhibitors as a starting point for directed differentiation. As a proof of concept, we focused our efforts on two specific cell/tissue types that have proven difficult to generate efficiently and reproducibly from mouse embryonic stem cells: definitive endoderm and neural organoids. We present new protocols for rapid generation of nearly pure definitive endoderm and forebrain-patterned neural organoids that model the development of prethalamic and hippocampal neurons. These differentiation models present new possibilities for combining mouse genetic tools with in vitro differentiation to characterize molecular and cellular mechanisms of embryonic development. © 2022. Published by The Company of Biologists Ltd.
Keywords: controlled study; nonhuman; animal cell; mouse; animal experiment; animal model; embryo development; in vitro study; cell culture; pluripotent stem cell; pluripotent stem cells; forebrain; nervous system development; nerve cell; endoderm; hippocampus; tissues; directed differentiation; wnt signaling; ectoderm; proof of concept; definitive endoderm; neural development; male; article; organoids; mouse embryonic stem cell; organoid; subthalamus
Journal Title: Development
Volume: 149
Issue: 20
ISSN: 0950-1991
Publisher: Company of Biologists  
Date Published: 2022-10-01
Start Page: dev200561
Language: English
DOI: 10.1242/dev.200561
PUBMED: 35899604
PROVIDER: scopus
PMCID: PMC10655922
DOI/URL:
Notes: Article -- Export Date: 3 October 2022 -- Source: Scopus
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MSK Authors
  1. Juliet Y Kim
    4 Kim
  2. Hyein Cho
    12 Cho
  3. Mohammed Tarek Islam
    2 Islam
  4. Rachel Glenn
    4 Glenn
  5. Yuan Lin
    1 Lin