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Pei and colleagues report that the oncogene c-Jun acts as a somatic cell reprogramming barrier, and that its truncated dominant-negative form can substitute for Oct4 in reprogramming.

Polycomb repressive complex 2 (PRC2) plays an essential role in development by modifying chromatin but what this means at a cellular level is unclear. Here, the authors show that ablation of PRC2 genes in human embryonic stem cells and in mice results in changes in pluripotency and the primed state of cells.

Duanqing Pei and colleagues show that BMP signaling to histone H3 lysine 9 methylation is a barrier to reprogramming somatic cells into induced pluripotent cells (iPSCs) and that its removal promotes the formation of fully reprogrammed iPSCs from pre-iPSCs. pre-iPSCs exhibit pluripotent properties but do not activate the core pluripotent network.

Cell fate decisions remain poorly understood at the molecular level. Here Ming et al. show that BMP4 as the signal diverting cell fate away from epiblast/pluripotency to hypoblast/primitive endoderm fate during JGES reprogramming by promoting the dissociation of SALL4 from NuRD.

The authors show that SARS-CoV-2-specific T cells in the lung are key to fighting infection and persist after viral clearance, contributing to long-term immunity and protection.

How transposable elements (TE) contribute to cell fate changes is unclear. Here, the authors generate a pipeline to quantify TE expression from single cell data. They show the dynamic expression of TEs from gastrulation to somatic cell reprogramming and human disease

N⁶-methyladenosine RNA and its reader YTHDC1 serve as a bridge to silencing retrotransposons through the RNA derived from these retrotransposons in mouse ES cells.

Human induced pluripotent stem cells reprogrammed from somatic cells by small molecules represent a promising approach for regenerative medicine. A recent study reveals a new chemical cocktail that can speed up reprogramming through epigenome remodeling.

Previous work suggested that histone demethylase JMJD3 is detrimental to somatic cell reprogramming. Here, the authors show that while JMJD3 has a context-independent detrimental effect on early stages of reprogramming, during late stages it activates epithelial and pluripotency genes together with Klf4.

This work describes the generation of a modification-free RNA library that resembles endogenous transcriptome sequence and expression level, which can be used as a negative control in epitranscriptomic sequencing methods to obtain high-confidence and quantitative maps of various RNA modifications.

Nucleoli are essential cellular sites for ribosome biogenesis that are formed by liquid-liquid phase separation. Here the authors show that METTL3/METTL14 maintain nucleoli integrity through mediating SUV39H1/2 degradation in human embryonic stem cells.

Multiple pluripotent states have been described in mouse and human stem cells. Here the authors describe trajectories during BMP4 induced primed to naïve transition, which bifurcates into naïve and trophoblast-like branches with a PGC-like intermediate at the naïve branch.

Direct RNA sequencing using nanopore platform can be used to detect N6-methyladenosine (m6A) modifications on mRNAs. Here the authors systematically compare tools used for m6A detection from nanopore direct sequencing.

High-quality genomes and single-cell atlases of auditory cortices from microbat and megabat species identify neuronal populations related to ultrasound perception and implicate complexin-1 as a key component of ultrasound transmission in mammals.

Current practice for the generation and maintenance of induced pluripotent stem cells (iPSCs) involves static culture in dishes. Two groups now report that mouse iPSCs can be generated efficiently in stirred suspension culture.

DNMT3A R882H and R882C are mutation hotspots in acute myeloid leukemia. This study describes the structural and functional consequences of the DNMT3A R882H/R882C mutations which can provide a strategy for therapy of the disease mutations.

Transposable elements (TEs) fulfill essential but poorly understood roles in genome organization and gene expression control. Here the authors show that the regulation of TEs occurs through overlapping epigenetic mechanisms that control the expression and chromatin signatures at TEs.

Yu, Zhou, Cao, He et al. show that BMP4 reconfigures the nuclear architecture during the transition from primed to naive pluripotency by targeting Zbtb7a and Zbtb7b, which encode proteins that mediate the opening of naive chromatin loci.

Somatic reprogramming involves both transcriptional and epigenetic resetting, but we don’t yet fully understand this process. Here they show that Jdp2, Glis1, Esrrb, and Sall4 can mediate reprogramming by recruiting the NuRD complex to close chromatin, highlighting a potential role in cell fate control.

The demethylase KDM5C, mutations in which often lead to intellectual disability, is identified as a crucial player in regulating the precise timing of neurodevelopment together with the WNT signalling pathway.

Emerging evidence suggests that exit from pluripotency is a regulated, rather than passive process. Here the authors identify a requirement for SS18-mediated Brg/Brahma-associated factors (BAF) chromatin remodeling complex assembly during exit from pluripotency, and that SS18 promotes BAF assembly through liquidliquid phase separation.

Oct4, along with Sox2 and Klf4 can induce pluripotency, but structurally similar factors like Oct6 cannot. Here, using pluripotency competent and incompetent factors, the authors show that Sox2 plays a dominant role in facilitating chromatin opening at Oct4 bound DNA early during reprogramming to pluripotency.

In mammals, DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B. Here the authors report the crystal structures of DNMT3B in complex with both CpG and CpA DNA, providing insight into the substrate-recognition mechanism underpinning the divergent genomic methylation activities of DNMT3A and DNMT3B.

Pei and colleagues show that introduction of the pluripotency reprogramming factors in sequence (Oct4–Klf4, c-Myc and finally Sox-2), rather than introducing them all together, increases reprogramming efficiency. This sequential delivery activates the epithelial-to-mesenchymal transition (EMT) before the mesenchymal-to-epithelial transition (MET), which was previously reported to occur during reprogramming. The authors also show that addition of EMT modulators influences reprogramming in a similar manner.

Qu et al. present a detailed three-dimensional spatial transcriptome atlas of all major organs in the mouse embryo at E13.5, providing a better understanding of organ development and cellular interactions during mammalian development.

The role of PHD finger protein 8 (PHF8) in anti-tumour immunity remains to be investigated. Here, the authors suggest PHF8 as an epigenetic checkpoint and show that targeting PHF8 induces a viral mimicry response enhancing anti-tumour immunity in colorectal cancer.

In mammals, de novo DNA methyltransferase DNMT3B is essential for establishing DNA methylation patterns during embryonic development. Here the authors provide a structure-function characterization of homo-oligomeric DNMT3B, revealing the molecular basis for its vulnerability to ICF mutations.

Zhang et al. report that the long noncoding RNA KCNQ1OT1 binds to double-stranded genomic DNA and to the heterochromatin protein HP1α to induce and maintain epigenetic silencing at repetitive DNA elements and guard against genomic instability and senescence.

Guo-Liang Xu, Duanqing Pei and colleagues show that during induced pluripotent cell reprogramming Tet1 regulates 5-hydroxymethylcytosine levels at loci critical for mesenchymal-to-epithelial transition in a vitamin C–dependent fashion. They also show that Tet1 either enhances or inhibits somatic cell reprogramming, depending on the absence or presence of vitamin C, respectively.

Conventional human pluripotent stem cells (hPSCs) fail to contribute to interspecies chimaeras when injected into mouse blastocysts. Here the authors show that forced expression of BMI1 overcomes apoptosis of hPSCs in blastocysts of mouse, rabbit and pig allowing them to contribute to chimaeras.

Wang and colleagues show that the transcription factor Hoxb5, which is expressed in uncommitted hematopoietic progenitor cells but is absent from committed B cells and T cells, can reprogram pro-pre-B cells into functional early T cell lineage progenitors.