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

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

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. Ectopic transcription factor expression can reprogram mouse fibroblasts to pluripotent or trophoblast stem cells. Here the authors apply multi-omics analyses to the induction of pluripotency and trophoblast stem cell state from fibroblasts, comparing these with the changes in transcriptome of early embryonic cells.

PLURIPOTENT stem cells; METHYLATION; STEM cells; TROPHOBLAST; CELL separation; DNA methylation; TRANSCRIPTION factors

Nature Communications, 2022, Vol 13, Issue 1, p1

2041-1723

Academic Journal

10.1038/s41467-022-31131-8