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Timms, Mena et al. present a multiplex CRISPR screening platform capable of assigning E3 ligases to their substrates and degrons at scale.

Bernabé-Rubio et al. report that dedifferentiation of Gata6⁺ epidermal cells occurs during wound healing or mechanical expansion of the epidermis through a Myc-dependent process that resembles reversal of differentiation.

Venkei et al. show that Y-linked Su(Ste) piRNAs are produced via 5′-to-3′ phased-biogenesis initiated by maternally deposited 1360/Hoppel-derived piRNAs, leading to silencing of Ste in the male germline.

Huang, Li, An, Yang, Cui et al. perform a single-cell multi-omics analysis of human spermatogenesis and identify a DNA demethylation event upon meiosis initiation, which is associated with meiotic recombination.

The molecular program of human germline commitment remains largely unknown. A new study delineates the multifaceted functions of DMRT1 in human germline development, particularly in the transition from early to late primordial germ cells.

Irie, Lee et al. report a role for DMRT1 in human germline development and show that induction of DMRT1 in primordial germ cell-like cells triggers germline commitment, but suppresses pluripotency genes, thus promoting the onset of gametogenesis.

Shirin Bahmanyar is an associate professor of molecular, cellular & developmental biology at Yale University, CT, USA. Shirin’s lab studies the organization of the endoplasmic reticulum (ER) and nuclear envelope, their dynamics throughout the cell cycle, and their relationship to lipid metabolism. We reached out to Shirin and were delighted to hear her thoughts on open questions in this field and to learn more about her research background and interests.

RNA modifications have emerged as key gene regulators. A new study shows that increased levels of reactive oxygen species in cancer induce widespread, sequence-specific modifications of guanines in the seed regions of microRNAs, altering the targets of those miRNAs and influencing tumorigenesis.

Embryonic diapause in development and paused pluripotency in embryonic stem cells result in a state of hypotranscription through mechanisms that remain unclear. A new study dissects the role of METTL3-deposited global m⁶A RNA methylation in mediating this transcriptional dormancy.

Collignon et al. report that Mettl3-mediated m⁶A RNA methylation promotes developmental pausing in embryonic stem cells and blastocysts by establishing transcriptional dormancy.

Eom, Peak, Park, Ahn and colleagues reveal and provide a comprehensive resource of 8-oxoguanine modifications in tumour microRNAs and show how they differentially influence malignancy progression in gliomas and hepatocellular carcinoma.

Genetic clearance of p16^high senescent cells or the use of senolytics improved the efficacy of stem cell reprogramming in vitro and in vivo, and helped establish induced pluripotent stem cells with features of experimental totipotency. When ablation of p16^high senescent cells was combined with partial four-factor reprogramming in vivo, we observed noticeable histopathological liver rejuvenation in aged mice.

Grigorash et al. report that depletion of p16^High cells promotes a totipotent-like state to improve somatic cell reprogramming efficiency through an S-adenosyl-l-methionine-dependent mechanism.

Kelly Stevens is an associate professor in the departments of Bioengineering and Laboratory Medicine & Pathology at the University of Washington. We spoke with her and discussed her work, her views on diversity and its importance, but also her personal struggles as an LGBT+ and disabled scientist.

In June 2023, the International Society for Stem Cell Research (ISSCR) released a report detailing standards for human stem cell research. We spoke to the co-chairs of the Steering Committee, Tenneille Ludwig, Senior Scientist and Director of the WiCell Stem Cell Bank, and Peter W. Andrews, Emeritus Professor at the University of Sheffield, and discussed the purpose and some of the basic aspects of these standards.