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

doi:10.1016/j.stemcr.2022.10.010

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

Department of Developmental Biology and Cancer Research

Research output: Contribution to journal › Article › peer-review

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 language	American English
Pages (from-to)	2643-2660
Number of pages	18
Journal	Stem Cell Reports
Volume	17
Issue number	12
DOIs	https://doi.org/10.1016/j.stemcr.2022.10.010
State	Published - 13 Dec 2022

Bibliographical note

Funding 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.

Funding 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.

Publisher Copyright:
© 2022 The Authors

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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10.1016/j.stemcr.2022.10.010

Cite this

Gropp, M., Waldhorn, I., Gil, Y., Steiner, D., Turetsky, T. T., Smith, Y., Sabag, O., Falick-Michaeli, T., Ram, S. E., & Reubinoff, B. E. (2022). Laminin111-based defined culture promoting self-renewing human pluripotent stem cells with properties of the early post-implantation epiblast. Stem Cell Reports, 17(12), 2643-2660. https://doi.org/10.1016/j.stemcr.2022.10.010

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

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.",

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author = "Michal Gropp and Ithai Waldhorn and Yaniv Gil and Debora Steiner and Turetsky, {Tikva Tako} and Yoav Smith and Ofra Sabag and Tal Falick-Michaeli and Ram, {Sharona Even} and Reubinoff, {Benjamin E.}",

note = "Funding 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. Funding Information: The study was supported by generous donations of Sidney and Judy Swartz, and Dan and Morrine Marantz, for the “Stem cells for women{\textquoteright}s health initiative.” RNA-seq was performed by the Genomic Applications Laboratory, Faculty of Medicine, Hebrew University of Jerusalem , Israel. Publisher Copyright: {\textcopyright} 2022 The Authors",

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AU - Steiner, Debora

AU - Turetsky, Tikva Tako

AU - Smith, Yoav

AU - Sabag, Ofra

AU - Falick-Michaeli, Tal

AU - Ram, Sharona Even

AU - Reubinoff, Benjamin E.

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ER -

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

Abstract

Bibliographical note

Keywords

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