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 () and Yosef Buganim ()
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Mohammad Jaber: Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School
Ahmed Radwan: Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School
Netanel Loyfer: The Hebrew University of Jerusalem
Mufeed Abdeen: Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School
Shulamit Sebban: Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School
Areej Khatib: Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School
Hazar Yassen: Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School
Thorsten Kolb: Group Genome Instability in Tumors, DKFZ
Marc Zapatka: German Cancer Consortium (DKTK)
Kirill Makedonski: Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School
Aurelie Ernst: Group Genome Instability in Tumors, DKFZ
Tommy Kaplan: Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School
Yosef Buganim: Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-21

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31131-8

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