Letters

Gerber-Ferder et al. show that non-metastatic breast tumours remotely reprogram the bone marrow stroma and instruct the myeloid differentiation of long-term haematopoietic stem cells.

Dai et al. show that the transcription factor ATFS-1 interferes with mitochondrial pre-initiation transcription complex assembly and promotes mitochondrial DNA repair, thereby reducing age-dependent mitochondrial DNA damage in Caenorhabditis elegans.

Chung et al. identify the protein spartin, linked to Troyer syndrome, as a lipophagy receptor for lipid droplet clearance in vitro and in vivo. The data suggest that impaired lipid droplet turnover may contribute to Troyer syndrome development.

Systematic infection of a human multi-organoid system shows that deficiency in the host factor CIART impairs SARS-CoV-2 infection through downregulation of the RXR pathway and subsequent impairment of fatty-acid synthesis.

Griess et al. determine the lipid signatures of pancreatic islets in type 2 diabetes models. They define a lipid environment linking the endoplasmic reticulum–Golgi transport protein Tmed2 to the proinsulin processing enzyme Pcsk1 to ensure insulin production.

Cockburn et al. report that epidermal differentiation is a multi-day process through which cells undergo a continuum of transcriptional alterations initiated independently of cell cycle exit.

Kuiper et al. and Prophet et al. implicate DNAJB6/HSP70 chaperone activities in the biogenesis of the nuclear pore complex permeability barrier and find that disease-linked nuclear envelope blebs are enriched in nucleoporin and chaperone condensates.

Bao et al. report that a cadherin code regulates the assembly and sorting of the first three cell lineages during mammalian development and can be manipulated to enhance the efficiency of synthetic embryogenesis.

Hao et al. describe an RNA-editing-independent role for ADAR1 in driving senescence. Autophagy downregulates ADAR1 in aged tissues, decreasing the binding of ADAR1 partner HuR to target mRNAs, including SIRT1. Loss of SIRT1 enhances p16^INK4a levels.

Arya et al. identify a pathway for exosome generation in immune cells that originates at the nuclear envelope and is facilitated by nSMase1-mediated generation of ceramide.

Zhang et al. identify that a group of PP2C phosphatases is responsible for direct sensing of CO₂ in the environment via phase separation of an intrinsically disordered region, which is a conserved mechanism across various species.

Huang et al. report that Tetraspanin proteins assemble a rigid ring structure around the damaged plasma membrane to prevent the wound from expanding, thus facilitating membrane repair by the ESCRT machinery and other repair factors.16:58

Yamazaki et al. show that cell cycle-regulated changes in hyperphosphorylation of Ki-67 and NPM1 modulate alternating charge blocks in these proteins, which defines their propensity for liquid–liquid phase separation at chromatin.

Luff et al. report a distinct human mesoderm cell population that generates definitive haemogenic endothelium in a retinoic acid-dependent manner, thus highlighting the dependence of haematopoietic ontogeny on retinoic acid-responsive mesoderm.

Merino et al. report that the cell-death factor Flower can control responses to morphogen gradients and thus has a role in gradient scaling.

Bellodi, Dimitriou and colleagues report that pseudouridine-modified transfer-RNA fragments modulate the translation of transcripts sharing pyrimidine-enriched sequences at their 5′ untranslated regions and their dysregulation impacts myelodysplastic syndrome pathogenesis.

Passarelli et al. identify leucyl-tRNA synthetase (LARS) as a critical tumour suppressor that upregulates translation of growth-inhibitory genes, including EMP3 and GGT5, thereby impairing breast cancer development.

Pinho et al. show that VCAM1 and MHC-I cooperate to provide a ‘don’t-eat-me’ signal that prevents haematopoietic stem cells clearance by mononuclear phagocytes, and also that VCAM1 can be hijacked by cancer cells to escape innate immune surveillance.

Döhla et al. show that selectively and asymmetrically inherited mitochondria impose a metabolic bias on progeny in mammary stem-like cells that alters the balance between stem cell self-renewal and differentiation.

Zhang et al. identify ALKBH7 as the demethylase of mitochondrial pre-tRNAs that regulates nascent mitochondrial RNA processing and translation. ALKBH7 loss impairs mitochondrial functions including fatty acid oxidation, leading to obesity.