PT  - JOURNAL ARTICLE
AU  - Mohammad Jaber
AU  - Ahmed Radwan
AU  - Netanel Loyfer
AU  - Mufeed Abdeen
AU  - Shulamit Sebban
AU  - Thorsten Kolb
AU  - Marc Zapatka
AU  - Kirill Makedonski
AU  - Aurelie Ernst
AU  - Tommy Kaplan
AU  - Yosef Buganim
TI  - Comparative Parallel Multi-Omics Analysis During the Induction of Pluripotent and Trophectoderm States
AID  - 10.1101/2020.09.27.315259
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.27.315259
4099  - http://biorxiv.org/content/early/2020/09/28/2020.09.27.315259.short
4100  - http://biorxiv.org/content/early/2020/09/28/2020.09.27.315259.full
AB  - Following fertilization, totipotent cells divide to generate two compartments in the early embryo: the inner cell mass (ICM) and trophectoderm (TE). It is only at the 32-64 -cell stage when a clear segregation between the two cell-types 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. We conducted a comparative parallel multi-omics analysis on cells undergoing reprogramming to Induced pluripotent stem cells (iPSCs) and induced trophoblast stem cells (TSCs), and examined their transcriptome, methylome, chromatin accessibility and activity and genomic stability. Our analysis revealed that cells undergoing reprogramming to pluripotency and TSC state exhibit specific trajectories from the onset of the process, suggesting ‘V’-shaped model. Using these analyses, not only we could describe in detail the various trajectories toward the two states, we also identified previously unknown stage-specific reprogramming markers as well as markers for faithful reprogramming and reprogramming blockers. 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 specific regions are initially open but then retain inactive by the elimination of the histone mark, H3K27ac.Competing Interest StatementThe authors have declared no competing interest.