Using live imaging to study transcription of dosage-compensated X chromosome genes at single-cell resolution, Forbes Beadle et al. show that transcriptional bursts have higher amplitude in male embryos compared with females. This gender cue is integrated with transcription factor concentration, which regulates burst frequency, to establish the transcriptional response.

Using nonhuman primate models, Nash et al. show that maternal Western-style diet provokes reprogramming of fetal hematopoietic stem and progenitor cells to transmit pro-inflammatory memory to myeloid cells for years after weaning, even when offspring are fed a conventional diet, predisposing these offspring to inflammatory disease across the lifespan.

Steiner et al. demonstrate that PTEN deletion in luminal prostate cell causes an expansion of transformed LY6D+ progenitor cells with intrinsic castration-resistant properties through autocrine AREG-mediated MAPK activation. Pharmacological interference of MAPK pathway overcomes the castration-resistance properties of LY6D+ cells, providing a rationale to target pre-existent castration-resistant…

Smits et al. report that TLX3 chromosomal translocations in T cell acute lymphoblastic leukemia patients recurrently include intervening CTCF-binding sites in the breakpoint area. Pressure to acquire inactivating aberrations in CTCF abrogate consequential enhancer insulation that promotes TLX3 promoter to BCL11B enhancer looping boosts higher oncogene expression levels and leukemia burden.

Using statistically principled analyses of biophysical models, Kim et al. show that the input-output transformation of a CA1 neuron is best captured by two distinct functional architectures operating in parallel. These architectures are mostly associated with NMDA versus dendritic Na+ channel signaling, controlling subthreshold fluctuations versus action potential timing, respectively.

Using multi-omics approaches in conjunction with detailed imaging, Nigro et al. find that exercise training promotes iWAT remodeling through changes in ECM, vascularization, and innervation. Moreover, they identify robust cell-type-specific adaptations in response to exercise that, in combination with structural changes, result in a healthier adipose tissue phenotype.

Saavedra-Peña et al. show that estradiol cycling regulates adipocyte formation in female mice by stimulating ERα-dependent proliferation of adipocyte precursor cells (APCs) at the onset of high-fat diet feeding. This estradiol-stimulated mechanism results in exacerbated obesity due to an increase in adipocyte formation.

Schofield and Hahn present a large-scale reporter assay measuring transcription of many combinations of yeast upstream activating sequences (UASs) and gene promoters. Their results suggest that UASs display both intrinsic activating potential and varying degrees of promoter specificity and that UASs and promoters both contribute to gene-specific regulation by transcriptional cofactors.

Kassardjian et al. engineer and characterize a modular vaccine scaffold for the delivery of antigen to MHC class II on antigen-presenting cells. This protein vaccine induces broad sarbecovirus neutralizing antibody responses and protects from SARS-CoV-2 viral challenge independently of adjuvant co-administration.

Kim et al. show cell-type-specific properties of spatial firing in the dentate gyrus by recording from single cells as mice freely explored distinct environments. These findings support the role of both granule cells and mossy cells in global remapping and orthogonalization (pattern separation) of spatial representations in dentate gyrus.