Rif1 and Hmgn3 regulate the conversion of murine trophoblast stem cells

Zhang, Wenhao; Yao, Chunmeng; Luo, Yanrui; Li, Qian; Zhao, Qian; Zhao, Yiding; Wang, Yuna; Geng, Mengyang; Wang, Qing; Xu, Mei; Sun, Shengyi; Wu, Dan; Gao, Qian; Wu, Xudong; Shuai, Ling

doi:10.1016/j.celrep.2022.110570

Cited by 16 publications

(17 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When the activators such as DUX are no longer in place, this default program ensures the accuracy and unidirectionality of differentiation. Consistent with this, both Rif1 and Mga in the PRC1.6 complex have been reported to limit mESCs to acquire extraembryonic cell fates (Qin et al 2021;Zhang et al 2022). Given their relatively high mRNA abundance in the 2C stage embryo as well as the spontaneously arisen 2C-like cells, the activity of this module is probably harnessed at the protein level.…”

Section: Discussionmentioning

confidence: 65%

Rif1 interacts with non-canonical polycomb repressive complex PRC1.6 to regulate mouse embryonic stem cells fate potential

Chen

et al. 2022

Cell Regen

View full text Add to dashboard Cite

Mouse embryonic stem cells (mESCs) cycle in and out of a transient 2-cell (2C)-like totipotent state, driven by a complex genetic circuit involves both the coding and repetitive sections of the genome. While a vast array of regulators, including the multi-functional protein Rif1, has been reported to influence the switch of fate potential, how they act in concert to achieve this cellular plasticity remains elusive. Here, by modularizing the known totipotency regulatory factors, we identify an unprecedented functional connection between Rif1 and the non-canonical polycomb repressive complex PRC1.6. Downregulation of the expression of either Rif1 or PRC1.6 subunits imposes similar impacts on the transcriptome of mESCs. The LacO-LacI induced ectopic colocalization assay detects a specific interaction between Rif1 and Pcgf6, bolstering the intactness of the PRC1.6 complex. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis further reveals that Rif1 is required for the accurate targeting of Pcgf6 to a group of genomic loci encompassing many genes involved in the regulation of the 2C-like state. Depletion of Rif1 or Pcgf6 not only activates 2C genes such as Zscan4 and Zfp352, but also derepresses a group of the endogenous retroviral element MERVL, a key marker for totipotency. Collectively, our findings discover that Rif1 can serve as a novel auxiliary component in the PRC1.6 complex to restrain the genetic circuit underlying totipotent fate potential, shedding new mechanistic insights into its function in regulating the cellular plasticity of embryonic stem cells.

show abstract

Section: Discussionmentioning

confidence: 65%

Rif1 interacts with non-canonical polycomb repressive complex PRC1.6 to regulate mouse embryonic stem cells fate potential

Chen

et al. 2022

Cell Regen

View full text Add to dashboard Cite

show abstract

“…Previously, some important regulatory genes have been found in mice, such as Cdx2 and Rif1 . Knocking out Rif1 plays critical roles in the regulation of trophoblast cells in mice 68 . Notch and Hippo signalling pathways cross talk to activate Cdx2 expression in mouse preimplantation embryos and promote the specialization of trophectoderm 69 .…”

Section: Discussionmentioning

confidence: 99%

“…Knocking out Rif1 plays critical roles in the regulation of trophoblast cells in mice. 68 Notch and Hippo signalling pathways cross talk to activate Cdx2 expression in mouse preimplantation embryos and promote the specialization of trophectoderm. 69 Overexpressing Cdx2 converted haploid ESCs to TSCs, 70 suggesting Cdx2 influenced the pluripotency.…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor induces a trophectoderm lineage transcriptome resembling that of human embryos during reconstruction of blastoids from extended pluripotent stem cells

Zhang

et al. 2022

Cell Proliferation

View full text Add to dashboard Cite

Objectives: This study aims to optimize the human extended pluripotent stem cell (EPSC) to trophectoderm (TE)-like cell induction with addition of EGF and improve the quality of the reconstructing blastoids.Materials and Methods: TE-like cells were differentiated from human EPSCs. RNAseq data analysis was performed to compare with TE-like cells from multiple human pluripotent stem cells (hPSCs) and embryos. A small-scale compound selection was performed for optimizing the TE-like cell induction and the efficiency was characterized using TE-lineage markers expression by immunofluorescence stanning. Blastoids were generated by using the optimized TE-like cells and the undifferentiated human EPSCs through three-dimensional culture system. Single-cell RNA sequencing was performed to investigate the lineage segregation of the optimized blastoids to human blastocysts.Results: TE-like cells derived from human EPSCs exhibited similar transcriptome with TE cells from embryos. Additionally, TE-like cells from multiple naive hPSCs exhibited heterogeneous gene expression patterns and signalling pathways because of the incomplete silencing of naive-specific genes and loss of imprinting. Furthermore, with the addition of EGF, TE-like cells derived from human EPSCs enhanced the TE lineage-related signalling pathways and exhibited more similar transcriptome to human embryos. Through resembling with undifferentiated human EPSCs, we Yingying Zhang and Chenrui An contributed equally to this research.

show abstract

“…On the other hand, the transition of TSCs from PSCs is actively investigated in developmental biology, including in mice. Interestingly, unlike human TSCs, mouse TSCs are not derived directly from embryonic stem cells (ESCs) under culture medium ( Peng et al., 2019 ; Zhang et al., 2022 ). But, mouse special genetic background, including overexpression (OE) of Cdx2 , Hmgn3 OE, knockout (KO) of Rif1, or p53 KO, could facilitate the conversion of TSCs from ESCs ( Peng et al., 2019 ; Zhang et al., 2022 ).…”

Section: Before You Beginmentioning

confidence: 99%

“…Interestingly, unlike human TSCs, mouse TSCs are not derived directly from embryonic stem cells (ESCs) under culture medium ( Peng et al., 2019 ; Zhang et al., 2022 ). But, mouse special genetic background, including overexpression (OE) of Cdx2 , Hmgn3 OE, knockout (KO) of Rif1, or p53 KO, could facilitate the conversion of TSCs from ESCs ( Peng et al., 2019 ; Zhang et al., 2022 ). So human PSC-to-TSC transition provides an insight for direct derivation of TSCs from mouse ESCs and a model for uncovering cell fate decisions of early embryonic development.…”

Section: Before You Beginmentioning

confidence: 99%

Protocol to derive human trophoblast stem cells directly from primed pluripotent stem cells

Wei¹,

Xiao²,

Ma³

et al. 2022

STAR Protocols

View full text Add to dashboard Cite

Rif1 and Hmgn3 regulate the conversion of murine trophoblast stem cells

Cited by 16 publications

References 37 publications

Rif1 interacts with non-canonical polycomb repressive complex PRC1.6 to regulate mouse embryonic stem cells fate potential

Rif1 interacts with non-canonical polycomb repressive complex PRC1.6 to regulate mouse embryonic stem cells fate potential

Epidermal growth factor induces a trophectoderm lineage transcriptome resembling that of human embryos during reconstruction of blastoids from extended pluripotent stem cells

Protocol to derive human trophoblast stem cells directly from primed pluripotent stem cells

Contact Info

Product

Resources

About