Nuclear m^(6)A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos

N^(6)-methyladenosine(m^(6)A)on chromosome-associated regulatory RNAs(carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.Here,we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells(ESCs),which highly depends on the m^(6)A-binding ability.Ythdcl is required for sufficient rRNA synthesis and repression of the 2-cell(2C)transcriptional program in ESCs,which recapitulates the transcriptome regulation by the LINE1 scaffold.Detailed analyses revealed that YTHDC1 recognizes m^(6)A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1.Moreover,the establishment of H3K9me3 on 2C-related retrotrans-posons is interrupted in Ythdcl-depleted ESCs and inner cell mass(ICM)cells,which consequently increases the transcriptional activities.Our study reveals a role of m^(6)A in regulating the RNA scaffold,providing a new model for the RNA-chromatin cross-talk.

Lessons from expanded potential of embryonic stem cells:Moving toward totipotency

Embryonic stem cells possess fascinating capacity of self-renewal and developmental potential,leading to significant progress in understanding the molecular basis of pluripotency,disease modeling,and reprogramming technology.Recently,2-cell-like embryonic stem cells(ESCs)and expanded potential stem cells or extended pluripotent stem cells(EPSCs)generated from early-cleavage embryos display some features of totipotent embryos.These cell lines provide valuable in vitro models to study underlying principles of totipotency,cell plasticity,and lineage segregation.In this review,we summarize the current progress in this filed and highlight the application potentials of these cells in the future.

Correction to:Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos

CORRECTION TO:PROTEIN CELL(2021)HTTPS://DOI.ORG/10.1007/S13238-021-00837-8 In the original publication of the article figure 1 is incorrectly published.The correct Figure 1 is provided in this correction.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit https://creativecommons.org/licenses/by/4.0/.

Xrcc1增强碱基切除修复能力进而提高诱导多能干细胞基因组稳定性和多能性的研究

诱导多能干细胞(iPSC)因其强大的自我更新和分化能力而具有广阔的应用前景.然而,多个研究表明体细胞诱导重编程过程会引入数以千计的遗传畸变,进而带来临床应用的安全性问题,已有前期研究证明单核苷酸变异(SNVs)的逐渐积累会致使iPSC丧失发育潜能,但致使SNVs产生并积累的原因还尚未探明.本研究通过对不同DNA损伤修复通路的筛选验证后,发现重编程过程早中期碱基切除修复(BER)效率的不足是导致SNVs积累的重要原因,进一步的研究发现XRCC1可以显著增强重编程前中期的BER,从而降低引入的SNVs,提高iPSC基因组的稳定性.同时,XRCC1介导的BER增强也提高了体细胞诱导重编程的效率.更为重要的是,体内嵌合体实验证实高效的BER可以显著提高iPSC的质量.综上,该研究可以有效提高iPSC基因组的稳定性和多能性,为其临床应用的安全性提供了新思路.