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Through CRISPR–Cas9 screen, Dev et al. identified that SHLD1/2 inhibition contributes to PARP-inhibitor resistance. Mechanistically, SHLDs promote non-homologous end-joining and antagonize homologous recombination.
Using a heterokaryon system, Mai et al. demonstrate that NKX3-1 is downstream of IL-6–STAT3, regulates endogenous OCT4 expression during human iPSC reprogramming, and can also substitute for exogenous OCT4 in the reprogramming cocktail.
Urra et al. discover that IRE1α, an ER stress mediator, interacts with
filamin A and controls actin dynamics and cell migration in mouse, Drosophila and zebrafish models in a manner independent
of its canonical function.
Using electron and three-dimensional structured illumination microscopy methods, Jana et al. characterize the ciliary base in four different cilia types in Drosophila, discovering structural and protein component differences that may be linked to the diversified functions of cilia.
Bardeesy and colleagues show that mutant GNAS suppresses salt-inducible kinases by activating PKA, leading to lipid remodelling and pancreatic tumourigenesis
Lassard et al. demonstrate a relationship between cellular senescence and perturbed ribosome biogenesis and find that the ribosomal protein S14 is an inhibitor of CDK4, inducing an Rb-dependent cell cycle arrest.
Garcia-Bermudez et al. and Sullivan et al. show that endogenous aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours, and that metformin depletes aspartate to limit tumour growth.
Garcia-Bermudez et al. and Sullivan et al. show that endogenous aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours, and that metformin depletes aspartate to limit tumour growth.
Using a multi-tier scRNA-seq and CRISP-seq approach, Giladi et al. define a transcriptional signature for the naive haematopoietic stem cell state, and follow progenitor plasticity and fate commitment under the influence of cytokines and growth factors.
Signalling by the energy sensor kinase AMPK is generally tumour suppressive, but Chhipa et al. show that AMPK is upregulated in glioblastoma, where it phosphorylates CREB1 to enhance HIF1α and GABPA transcription and to support tumour bioenergetics.
Using scCOOL-seq, Li et al. simultaneously characterize the DNA methylation and chromatin accessibility of the same cell during human preimplantation development.
Sacristan et al. show that the dynein adaptor Spindly facilitates oligomerisation of the RZZ complex to expand the kinetochore, after which Spindly-associated dynein compacts the kinetochore to allow for faithful chromosome segregation.
Gao et al. provide a comprehensive single-cell transcriptomic resource of four organs from the human fetal gastrointestinal tract and adult large intestine.
Duan et al. find that the membrane skeleton protein spectrin is required for myoblast fusion in Drosophila, accumulating in a mechanosensitive manner in the receiving partner during cell–cell fusion to modulate adhesion and protrusion events.
Reeves et al. use a multistage skin carcinogenesis mouse model and multicoloured lineage tracing to analyse the different patterns of clonal evolution and behaviour seen in progressing and non-progressing papillomas.
Knapp et al. analyse the heterogeneous molecular profiles and functions of CD49f human cord blood haematopoietic stem cells and report that a subset with CD33 expression has improved regenerative activity.
Monitoring growing epithelial cells through the cell cycle, Uroz et al. find that cell–cell tension and cell–matrix traction forces differ across the cell cycle and affect cell cycle duration, the G1–S transition and mitotic rounding.
Lilja et al. report that multipotent mouse embryonic mammary cells become lineage restricted as early as embryonic day 12.5 during development in a potency switch regulated by Notch1 signalling.
Wuidart et al. show that the mammary gland develops from embryonic multipotent progenitors that switch from multipotency to unipotency and express a unique gene signature. ΔNp63 promotes their basal fate and also reprograms adult luminal cells.
Fang et al. identify a PAX5–OCT4–PRDM1 transcriptional network that acts as a developmental switch in the transition from human pluripotent stem cells to the primordial germ cell lineage.