Stabilization of HESCs in Two Distinct Substates Along the Continuum of Pluripotency

Overview

Journal iScience

Publisher Cell Press

Date 2022 Nov 21

PMID 36404921

Authors

Chen Dekel

Robert Morey

Jacob Hanna

Louise C Laurent

Dalit Ben-Yosef

Hadar Amir

Affiliations

Soon will be listed here.

Abstract

A detailed understanding of the developmental substates of human pluripotent stem cells (hPSCs) is needed to optimize their use in cell therapy and for modeling early development. Genetic instability and risk of tumorigenicity of primed hPSCs are well documented, but a systematic isogenic comparison between substates has not been performed. We derived four hESC lines in naive human stem cell medium (NHSM) and generated isogenic pairs of NHSM and primed cultures. Through phenotypic, transcriptomic, and methylation profiling, we identified changes that arose during the transition to a primed substate. Although early NHSM cultures displayed naive characteristics, including greater proliferation and clonogenic potential compared with primed cultures, they drifted toward a more primed-like substate over time, including accumulation of genetic abnormalities. Overall, we show that transcriptomic and epigenomic profiling can be used to place human pluripotent cultures along a developmental continuum and may inform their utility for clinical and research applications.

Citing Articles

Molecular Mechanisms Underlying Pluripotency and Self-Renewal of Embryonic Stem Cells.

Varzideh F, Gambardella J, Kansakar U, Jankauskas S, Santulli G Int J Mol Sci. 2023; 24(9).

PMID: 37176093 PMC: 10179698. DOI: 10.3390/ijms24098386.

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