It is with no small measure of sadness that we reflect on the life of Professor J. Michael Bishop, who passed away in March at age 90. Mike was a towering figure in biomedical science whose scientific leadership and discoveries had enormous and lasting impact on the University of California, San Francisco (UCSF)—his home institution for over 50 years—and on the biomedical sciences nationally and internationally. Indeed, Mike and Harold Varmus’ 1976 co-discovery of the cellular origins of the avian retroviral oncogene v-Src reshaped our understanding of the genetic underpinnings of cancer and led to safe and effective treatment strategies for numerous human malignancies.

Iron abundance alone does not determine ferroptosis sensitivity. In this issue of Cell, Sharma and colleagues identify polyamines as endogenous metabolic buffers that reduce the chemical accessibility of labile iron, revealing an unexpected function for one of the cell’s most abundant metabolite classes while raising new questions about the organization of intracellular iron metabolism.

Peripheral serotonergic signaling has been implicated in diverse physiological processes, yet its role in coordinating glial-immune interactions remains poorly understood. In this issue of Cell, Wen and colleagues identify enteric glial cells as critical effectors of peripheral 5-HT2AR agonism, uncovering a serotonergic neuroimmune circuit that drives cytotoxic T cell-mediated immunity against colorectal cancer.

Fibrosis is a major contributor to disease and mortality yet lacks effective therapies. This review proposes that fibrotic states are maintained by chromatin-regulated circuits in fibroblasts and macrophages shaped by immune-stromal crosstalk and that rewiring this upstream regulatory logic offers a path beyond current antifibrotic approaches.

The Drosophila whole male central nervous system connectome enables end-to-end analysis of sensorimotor circuits. Comparison with existing female datasets shows that brain-wide wiring differences between the sexes are concentrated in higher centers.

The complete gustatory system and the full set of feeding motor neurons of adult Drosophila are mapped at synaptic resolution, enabling the identification of taste neuron types and their likely tastants and showing how valence-specific circuit motifs route taste to generate distinct feeding, neuroendocrine, and social outputs.

Tracing visual signals through the fly connectome provides a brain-wide view of visual organization, linking visual inputs to more than half of central-brain cell types through multisynaptic pathways. Estimates of the information available to each type generate testable hypotheses for thousands of physiologically uncharacterized cell types.

Ancient DNA from 149 individuals at 11 sites in Gansu, China, dated to around 4,700–3,000 years ago, reveals human population history during early transcontinental exchanges of agriculture and technology, as well as contemporary social practices, at the large Mogou cemetery.

Polyamines buffer labile iron, restraining its reactivity to suppress ferroptosis. Their depletion raises labile iron and creates synthetic lethality with GPX4 loss, revealing polyamine metabolism as an endogenous regulator of iron homeostasis.

(Cell 184, 296-298; January 21, 2021)

(Cell 153, 1379–1393; June 6, 2013)

By selectively targeting peripheral 5-HT2AR without inducing psychedelic effects, a non-brain-penetrant agonist boosts antitumor CD8+ T cell immunity and improves immunotherapy responses in preclinical models of colorectal cancer.

Basement membranes are scaffolds of proteins, like collagen, that give organs shape. During development, basement membranes must adapt to the growing organ. We infer how fast the basement membrane adapts by measuring collagen turnover. We find that perlecan, another basement membrane protein, regulates collagen turnover to control organ shape.

Cerebrospinal fluid (CSF) crosses arachnoid fenestrations near the olfactory bulbs to reach dural lymphatics that traverse the cribriform plate, connect to nasal lymphatics, and drain to cervical lymph nodes. Aging impairs this pathway, but intranasal VEGF-C restores the lymphatics and the CSF outflow.

PD-1+ T follicular helper-like cells drive B cell-associated pathology in multiple sclerosis. Programmable PD-1-targeting CAR T cells selectively eliminate these pathogenic CD4 T cells while delivering IL-10 at sites of inflammation, thereby suppressing neuroinflammation across preclinical models.

Chemically induced proximity of lysine acetyltransferases (KATs) with BCL6 reprograms epigenetic signaling to eliminate lymphoma tumors. Structural and mechanistic studies demonstrate that fortuitous protein-protein contacts convert proximity induction into targeted changes in chromatin, revealing a key mechanism by which small molecules can co-opt oncogenic transcriptional regulators to elicit malignant cell death.

Within the skin, glutamatergic neurons expressing neurofilament heavy chain (Nefh) play a role in aging. Loss of Nefh during aging drives skin fibroblast senescence and collagen loss, whereas glutamate supplementation improves skin aging phenotypes.

Corals harbor intracellular algal symbionts in specialized organelles that enable them to build diverse reef ecosystems. Corals and other cnidarians have repeatedly evolved this symbiosis through the co-option of lysosomal machinery to simultaneously support photosynthesis and extract photosynthetic products from the algae.

A deep-tissue spatial transcriptomics method simultaneously captures hundreds of hair follicles spanning organogenesis in mouse skin. Ordering follicles by molecular age transforms this snapshot into a map of organogenesis in both space and time, revealing the choreography of organ assembly and how it goes awry in genetically hairless mice.

Single-cell whole-genome sequencing reveals a shared pattern of excessive somatic mutations across C9ORF72 ALS, C9ORF72 FTD, and Alzheimer’s disease, dominated by 2-bp deletions. These mutations arise from aberrant topoisomerase 1 (TOP1)-mediated mutagenesis linked to oxidative DNA damage, identifying a unifying mechanism of neuronal genomic instability in neurodegeneration.