Mapping of genome-wide DNA methylation patterns in human islet alpha and beta cells highlights age- and type 2 diabetes-dependent adaptations, and CRISPR-based epigenetic editing strategies validate k...

Mapping of genome-wide DNA methylation patterns in human islet alpha and beta cells highlights age- and type 2 diabetes-dependent adaptations, and CRISPR-based epigenetic editing strategies validate k...

AAT-overexpressing MSCs reverse new-onset diabetes in NOD mice by enhancing Treg expansion, suppressing pathogenic CD4+ and CD8+ T cells, and improving immune communication in pancreatic tissues. This...

Glycemic fluctuations trigger a fast-slow oscillation switch in islet Ca2+ activity in vivo. We show that this rhythmicity depends on α-δ cell interactions, is impaired in diabetes, and is restored by...

Pilley et al. describe how metabolite levels change in 12 organs from male and female mice across five ages, spanning adolescence to old age. They reveal that organs show distinct age- and sex-specifi...

Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that na...

PROTACs induce degradation by bridging a target protein and E3 ubiquitin ligase. Here, authors show that protein interface frustration correlates with cooperativity, offering a structural metric to prioritize PROTAC candidates prior to synthesis.

β-cell dysfunction and dedifferentiation towards an α-cell-like phenotype are hallmarks of type 2 diabetes. Her,e the authors detect five α-cell subpopulations, find differences between healthy and diabetic donors, and identify SMOC1 as an inducer of human β-cell dysfunction and dedifferentiation.

Clarke et al. reveal that non-hematopoietic cells, fibroblastic in nature, located outside the islet of Langerhans, spontaneously present β cell antigens. These cells, associated with the post-capilla...

Hypoxia impairs the efficacy of stem cell-derived islet cell therapy, making it a potential barrier for treatment of type 1 diabetes. Wang et al. identify EDN3 as a key factor that preserves β cell id...

Pregnancy is associated with physiological adaptations that affect virtually all organs, enabling the mother to support the growing fetus and placenta while withstanding the demands of pregnancy. As a...

T and B cells cooperate in meningeal eLFs to promote differentiation and clonal expansion of B cells and reactivation of CNS T cells.

Xenotransplantation is a promising option when allogeneic donors are unavailable but hampered by a more stringent immunological barrier. Here authors show that hypoimmune cells engineered to overcome ...

Leveraging Finnish nationwide multi-generational registers and the biobanks of FinnGen, Wang, Liu, et al. investigated the effect of parental autoimmune diseases on offspring T1D. Their creative and r...

Starting at middle age, adults often suffer from visceral adiposity and associated adverse metabolic disorders. Lineage tracing in mice revealed that adipose progenitor cells (APCs) in visceral fat un...

The sequential order of NGN3 and NEUROD1 expression shapes their pioneer functions in pancreatic endocrine differentiation.

The sequential order of NGN3 and NEUROD1 expression shapes their pioneer functions in pancreatic endocrine differentiation.

Targeting transcription factors with small molecules remains a significant challenge in drug discovery. Here, the authors present a structure-based approach to stabilize ChREBPα/14-3-3 interactions, s...

The pancreatic vasculature displays significant heterogeneity, with the islets perfused by a specialized microcirculation with greater density than the surrounding acinar tissue. Using single-cell RNA...

Arthur and Nguyen et al. leverage iPSCORE, a large collection of three early developmental-like tissues with corresponding molecular datasets (RNA-seq, ATAC-seq, H3K27ac ChIP-seq), to map over 70,000 ...

Aims/hypothesis Diabetic kidney disease (DKD) features intrarenal inflammation, in which T cells play a part. Hypoxia-inducible factor-1α (HIF-1α), a key transcription factor regulating cellular respo...

Spontaneous transdifferentiation of pancreatic glucagon-producing alpha to insulin secreting beta cells has been observed in mouse but not in human islets1. Here, we analyzed the largest single cell d...

β cell dedifferentiation underlies diabetes mellitus in Wolfram syndrome, and Txnip inhibition prevents β cell regression in Wfs1-deficient mice.

Mitochondrial damage is a hallmark of metabolic diseases, including diabetes, yet the consequences of compromised mitochondria in metabolic tissues are often unclear. Here, we report that dysfunctiona...

Activation of innate immune signaling occurs during the progression of immunometabolic diseases, including type 2 diabetes (T2D), yet the impact of innate immune signaling on glucose homeostasis is co...

Small nucleolar RNAs (snoRNAs) are a class of non-coding RNA molecules whose precursor transcripts are capped and polyadenylated. However, these end modifications are detrimental to snoRNA function an...

Loss-of-function variants in MDA5, a key sensor of double-stranded RNA from viruses and retroelements, have been associated with protection from type 1 diabetes (T1D) in genome-wide association studie...

This Review highlights recent advances in the identification of small-molecule mediators of beta cell regeneration, discussing the diverse pathways and cellular processes altered by these compounds.

Biological sex differences in morbidity upon influenza A virus (IAV) infection are linked to stronger IFN-centered immune responses in females, yet the regulatory role of sex hormone receptors in immu...

Numerous studies highlight the essential role of type I interferon (IFN) responses in type 1 diabetes. The absence of type I IFN signaling is associat…

The immune system shapes body metabolism, while interactions between peripheral neurons and immune cells control tissue homeostasis and immunity. However, whether peripheral neuroimmune interactions o...

In this Review the author summarizes the current approaches for antigen-specific therapies in the treatment of autoimmune disease and highlights the challenges that need to be addressed for successful...

Our study underscores the critical role of sex as a significant variable in T1D patients and T1D progressors, with discernible differences in cytokine levels observed only when stratified by sex. Det...

Xu Landén and colleagues conducted a unique study on human skin wound healing by inducing wounds in healthy donors and collecting wound-edge tissues at three healing stages. Transcriptome profiling from this study deepens our understanding of tissue repair mechanisms, paving the way for novel therapeutic targets to treat chronic wounds.

Glucagon is essential for glucose homeostasis during fasting and in diabetes, yet the mechanisms regulating its secretion are not fully understood. Long et al. demonstrate that famsin, a gut-secreted hormone, stimulates glucagon secretion through calcium mobilization, thereby promoting hepatic glucose production to maintain glucose homeostasis during fasting and in diabetes.

In autoimmune Type 1 diabetes (T1D), immune cells infiltrate and destroy the islets of Langerhans, islands of endocrine tissue dispersed throughout the pancreas. However, the contribution of cellular ...

Identification of an LGR5 as a marker for a tripotent stem/progenitor cell of the human fetal pancreas. Organoids derived from single LGR5+ cells are capable of long-term expansion in vitro and genera...