Kaibo Duan

Tissue macrophages have a split personality Resident tissue macrophages (RTMs) reside in various tissue-specific niches during development. They evince microenvironment-directed phenotypes that support host defense and tissue homeostasis. Chakarov et al. used single-cell RNA sequencing and fate-mapping of murine lung RTMs to interrogate RTM-subset heterogeneity, interrelationships, and ontogeny (see the Perspective by Mildner and Yona). In addition to alveolar macrophages, they identified two different interstitial macrophage populations. One population mostly abutted nerve fibers; the other population preferentially localized near blood vessels and appeared to support vessel integrity and inhibit inflammatory cell infiltration into tissues. Science , this issue p. eaau0964 ; see also p. 1154

Tracing development of the dendritic cell lineage Dendritic cells (DCs) are important components of the immune system that form from the bone marrow into two major cell lineages: plasmacytoid DCs and conventional DCs. See et al. applied single-cell RNA sequencing and cytometry by time-of-flight to characterize the developmental pathways of these cells. They identified blood DC precursors that shared surface markers with plasmacytoid DCs but that were functionally distinct. This unsuspected level of complexity in pre-DC populations reveals additional cell types and refines understanding of known cell types. Science , this issue p. eaag3009

Neutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1 + state. Reprogrammed dcTRAIL-R1 + neutrophils predominantly localize to a glycolytic and hypoxic niche at the tumor core and exert pro-angiogenic function that favors tumor growth. We found similar trajectories in neutrophils across multiple tumor types and in humans, suggesting that targeting this program may provide a means of enhancing certain cancer immunotherapies.