biorxiv.org

Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes - Nature Metabolism

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...

nature.com

Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes - Nature Metabolism

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...

nature.com

Taming Autoimmunity: Alpha-1 Antitrypsin Overexpressing Mesenchymal Stem/Stromal Cells Promote Regulatory T Cell Crosstalk to Reverse Diabetes

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...

cell.com

Glycemia shifts pancreatic islet rhythmicity by influencing interactions between δ cells and α cells

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...

cell.com

A metabolic atlas of mouse aging

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...

cell.com

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging

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...

science.org

Frustration in the protein-protein interface plays a central role in the cooperativity of PROTAC ternary complexes - Nature Communications

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.

nature.com

Human pancreatic α-cell heterogeneity and trajectory inference analyses reveal SMOC1 as a β-cell dedifferentiation gene - Nature Communications

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.

nature.com

JCI - Altered immune and metabolic molecular pathways drive islet cell dysfunction in human type 1 diabetes

jci.org

A vascular-associated fibroblastic cell controls pancreatic islet immunity

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...

cell.com

Improving cellular fitness of human stem cell-derived islets under hypoxia - Nature Communications

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...

nature.com

Pregnancy-induced metabolic reprogramming and regenerative responses to pro-aging stresses

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...

cell.com

T–B cell cooperation in ectopic lymphoid follicles propagates CNS autoimmunity

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

science.org

Inhibition of polymorphonuclear cells averts cytotoxicity against hypoimmune cells in xenotransplantation - Nature Communications

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 ...

nature.com

Effects of parental autoimmune diseases on type 1 diabetes in offspring can be partially explained by HLA and non-HLA polymorphisms

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...

cell.com

Distinct adipose progenitor cells emerging with age drive active adipogenesis

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...

science.org

The expression order determines the pioneer functions of NGN3 and NEUROD1 in pancreatic endocrine differentiation

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

science.org

The expression order determines the pioneer functions of NGN3 and NEUROD1 in pancreatic endocrine differentiation

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

science.org

Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity - Nature Communications

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...

nature.com

Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes - Nature Communications

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...

nature.com

Multiomic QTL mapping reveals phenotypic complexity of GWAS loci and prioritizes putative causal variants

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 ...

cell.com

High glucose/ChREBP-induced Hif-1α transcriptional activation in CD4+ T cells reduces the risk of diabetic kidney disease by inhibiting the Th1 response - Diabetologia

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...

tinyurl.com

Single-cell multiome analysis supports α-to-β transdifferentiation in human pancreas

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...

biorxiv.org

β cell dedifferentiation, the underlying mechanism of diabetes in Wolfram syndrome

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

science.org

Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues

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...

science.org

TRAF6 integrates innate immune signals to regulate glucose homeostasis via Parkin-dependent and -independent mitophagy

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...

biorxiv.org

RNase III cleavage signals spread across splice junctions enforce sequential processing of co-hosted snoRNAs

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...

biorxiv.org