Volume 25 Issue 10, October 2023

Recent findings ranging from genetics to structural biology, together with studies in human neurons, animal models and patient brains, implicate the retromer-dependent endosomal recycling pathway as both causal and common in Alzheimer’s disease.

Shirin Bahmanyar is an associate professor of molecular, cellular & developmental biology at Yale University, CT, USA. Shirin’s lab studies the organization of the endoplasmic reticulum (ER) and nuclear envelope, their dynamics throughout the cell cycle, and their relationship to lipid metabolism. We reached out to Shirin and were delighted to hear her thoughts on open questions in this field and to learn more about her research background and interests.

In this issue, Jason Shapiro, Hsiang-Chun (Jimmy) Chang and colleagues identify a conserved role for the iron-binding histone demethylase KDM3B in sensing iron levels and regulating mTORC1 through transcriptional repression of key components of the mTORC1 pathway. In this Q&A, we discuss this manuscript’s findings and publishing journey with first authors Jason Shapiro and Jimmy Chang and corresponding author Hossein Ardehali. Hossein is currently the director of the Center for Molecular Cardiology at the Feinberg School of Medicine at Northwestern University in Chicago; Jason is an MD candidate graduating in 2024 at the Feinberg School of Medicine; and Jimmy is a resident physician in the Department of Pediatrics at the Baylor College of Medicine in Houston.

Bone marrow endothelial cells deliver oxygen and nutrients and regulate bone formation and haematopoiesis in the surrounding microenvironment. A new study identifies a subtype of capillary that occurs exclusively in the epiphysis and displays unique characteristics that have a role in balancing osteogenesis and haematopoiesis.

The molecular program of human germline commitment remains largely unknown. A new study delineates the multifaceted functions of DMRT1 in human germline development, particularly in the transition from early to late primordial germ cells.

ESCRT-III seals holes in the nuclear envelope (NE). A study now shows that the Cmp7-directed ESCRT-III cascade that grommets and reseals NE holes after spindle pole body (SPB) extrusion at the end of fission yeast mitosis is complemented by the presence of a proteinaceous diffusion barrier to ensure NE integrity.

In many species, maternally deposited Piwi-interacting RNAs (piRNAs) deliver intergenerational epigenetic information to protect progeny from transposon expansion or invasion. However, Y-chromosome-encoded piRNAs cannot be passed from mothers to male offspring, yet mothers use autosomally encoded piRNAs to allow sons to utilize their Y chromosome to protect against ‘selfish’ elements.

Iga et al. perform single-cell RNA sequencing and identify a distinct bone marrow endothelial cell subtype that contributes to the acquisition of bone strength and offers a distinct haematopoietic stem cell niche.

Bernabé-Rubio et al. report that dedifferentiation of Gata6⁺ epidermal cells occurs during wound healing or mechanical expansion of the epidermis through a Myc-dependent process that resembles reversal of differentiation.

Irie, Lee et al. report a role for DMRT1 in human germline development and show that induction of DMRT1 in primordial germ cell-like cells triggers germline commitment, but suppresses pluripotency genes, thus promoting the onset of gametogenesis.

Zhang et al. report curved adhesions, which are integrin-based adhesions formed in response to membrane curvatures that can be imposed by the overlying extracellular matrix fibre geometry.

Ader et al. find a grommet-like role for ESCRTs distinct from their nuclear envelope sealing function after spindle pole body extrusion. The grommet works with spindle pole body components that establish a diffusion barrier to maintain compartmentalization.

Shapiro, Chang, et al. identify a conserved role for the iron-binding histone demethylase KDM3B in sensing iron levels and regulating mTORC1 through transcriptional repression of key mTORC1 pathway components.

Venkei et al. show that Y-linked Su(Ste) piRNAs are produced via 5′-to-3′ phased-biogenesis initiated by maternally deposited 1360/Hoppel-derived piRNAs, leading to silencing of Ste in the male germline.

Qu et al. identify and characterize reciprocal crosstalk between small-cell lung cancer cells and astrocytes, which mimics neuron–astrocyte interactions during brain development and promotes brain metastasis.

Huang, Li, An, Yang, Cui et al. perform a single-cell multi-omics analysis of human spermatogenesis and identify a DNA demethylation event upon meiosis initiation, which is associated with meiotic recombination.

Timms, Mena et al. present a multiplex CRISPR screening platform capable of assigning E3 ligases to their substrates and degrons at scale.