Laminin111-based defined culture promoting self-renewing human pluripotent stem cells with properties of the early post-implantation epiblast

Michal Gropp, Ithai Waldhorn, Yaniv Gil, Debora Steiner, Tikva Tako Turetsky, Yoav Smith, Ofra Sabag, Tal Falick-Michaeli, Sharona Even Ram, Benjamin E. Reubinoff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

In the mammalian embryo, a formative pluripotent phase is proposed to exist at the early post-implantation period, during the transition from the pre-implantation naive—to the post-implantation primed—epiblast. By recapitulating a laminin component of the extracellular matrix niche during embryonic formative transition, and defined culture conditions, we generated cultures highly enriched for self-renewing human pluripotent stem cells (hPSCs), exhibiting properties of early post-implantation epiblast cells. These hPSCs display post-implantation-epiblast gene expression profiles. FGF and TGF-β signaling maintain their self-renewal for multiple passages. They have inactive canonical Wnt signaling, do not express primitive streak markers, and are competent to initiate differentiation toward germline and somatic fates. hPSCs exhibiting early post-implantation epiblast properties may shed light on human embryonic PSCs development and may serve for initiating somatic and germ cell specification.

Original languageAmerican English
Pages (from-to)2643-2660
Number of pages18
JournalStem Cell Reports
Volume17
Issue number12
DOIs
StatePublished - 13 Dec 2022

Bibliographical note

Publisher Copyright:
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Keywords

  • canonical Wnt signaling
  • early post-implantation epiblast
  • formative pluripotency
  • germ cell specification
  • human pluripotency states
  • human pluripotent stem cells
  • laminin-111

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