Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states

Mohammad Jaber, Ahmed Radwan, Netanel Loyfer, Mufeed Abdeen, Shulamit Sebban, Areej Khatib, Hazar Yassen, Thorsten Kolb, Marc Zapatka, Kirill Makedonski, Aurelie Ernst, Tommy Kaplan*, Yosef Buganim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Following fertilization, it is only at the 32-64-cell stage when a clear segregation between cells of the inner cell mass and trophectoderm is observed, suggesting a ‘T’-shaped model of specification. Here, we examine whether the acquisition of these two states in vitro, by nuclear reprogramming, share similar dynamics/trajectories. Using a comparative parallel multi-omics analysis (i.e., bulk RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, RRBS and CNVs) on cells undergoing reprogramming to pluripotency and TSC state we show that each reprogramming system exhibits specific trajectories from the onset of the process, suggesting ‘V’-shaped model. We describe in detail the various trajectories toward the two states and illuminate reprogramming stage-specific markers, blockers, facilitators and TSC subpopulations. Finally, we show that while the acquisition of the TSC state involves the silencing of embryonic programs by DNA methylation, during the acquisition of pluripotency these regions are initially defined but retain inactive by the elimination of H3K27ac.

Original languageAmerican English
Article number3475
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - 17 Jun 2022

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© 2022, The Author(s).

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