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.
Bibliographical noteFunding Information:
The study was supported by generous donations of Sidney and Judy Swartz, and Dan and Morrine Marantz, for the “Stem cells for women's health initiative.” RNA-seq was performed by the Genomic Applications Laboratory, Faculty of Medicine, Hebrew University of Jerusalem, Israel. B.E.R. is a member of the journal's Editorial Board. He is a founder, holds shares, and is the Chief Scientific Officer of CellCure Neuroscience Ltd. The company did not fund the study presented in this manuscript and has no interest in its results. A patent application related to the data presented in this manuscript has been submitted.
The study was supported by generous donations of Sidney and Judy Swartz, and Dan and Morrine Marantz, for the “Stem cells for women’s health initiative.” RNA-seq was performed by the Genomic Applications Laboratory, Faculty of Medicine, Hebrew University of Jerusalem , Israel.
© 2022 The Authors
- canonical Wnt signaling
- early post-implantation epiblast
- formative pluripotency
- germ cell specification
- human pluripotency states
- human pluripotent stem cells