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...

Taming Autoimmunity: Alpha-1 Antitrypsin Overexpressing Mesenchymal Stem/Stromal Cells Promote Regulatory T Cell Crosstalk to Reverse Diabetes: Molecular Therapy www.cell.com/molecular-th...

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...

Glycemia shifts pancreatic islet rhythmicity by influencing interactions between δ cells and α cells: Cell Systems www.cell.com/cell-systems...

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...

A metabolic atlas of mouse aging: Cell Metabolism www.cell.com/cell-metabol...

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...

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging.
www.science.org/doi/10.1126/...

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.

Frustration in the protein-protein interface plays a central role in the cooperativity of PROTAC ternary complexes.
www.nature.com/articles/s41...

Thank you.

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.

Human pancreatic α-cell heterogeneity and trajectory inference analyses reveal SMOC1 as a β-cell dedifferentiation gene.
www.nature.com/articles/s41...

JCI - Altered immune and metabolic molecular pathways drive islet cell dysfunction in human type 1 diabetes www.jci.org/articles/vie...

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...

A vascular-associated fibroblastic cell controls pancreatic islet immunity.
www.cell.com/cell-reports...

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...

Improving cellular fitness of human stem cell-derived islets under hypoxia.
www.nature.com/articles/s41...

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...

Pregnancy-induced metabolic reprogramming and regenerative responses to pro-aging stresses: Trends in Endocrinology & Metabolism www.cell.com/trends/endoc...

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.

T–B cell cooperation in ectopic lymphoid follicles propagates CNS autoimmunity.
www.science.org/doi/10.1126/...

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 ...

Inhibition of polymorphonuclear cells averts cytotoxicity against hypoimmune cells in xenotransplantation.
www.nature.com/articles/s41...

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...

Effects of parental autoimmune diseases on type 1 diabetes in offspring can be partially explained by HLA and non-HLA polymorphisms.
www.cell.com/cell-genomic...

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...

Distinct adipose progenitor cells emerging with age drive active adipogenesis | Science www.science.org/doi/10.1126/...

#SkeletalMuscle #Mitophagy #ERPhagy

ACTA1-Cre::BNIP3L KO🐭muscle
👉Accumulated Mitochondria
👉⏬glycolytic myofiber ⏬oxidative fiber
👉⏫ #ERPhagy (ER-mCherry/GFP-LC3; ER-Emerald/LysoTracker) ⏬ER Ca2+
👉Centronuclear myopathy

@josephwgordon.bsky.social #Autophagy 2025
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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.

The expression order determines the pioneer functions of NGN3 and NEUROD1 in pancreatic endocrine differentiation | Science Advances www.science.org/doi/10.1126/...

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.

The expression order determines the pioneer functions of NGN3 and NEUROD1 in pancreatic endocrine differentiation | Science Advances www.science.org/doi/10.1126/...

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...

Excited to share our work in @naturecomms.bsky.social
We shows that molecular glues of the ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity. This could lead to new treatments for Diabetes by preserving beta cell function. www.nature.com/articles/s41...
#DiabetesResearch #BetaCells

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...

Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes.
www.nature.com/articles/s41...

Characterization of islet cells from people with type 1 #diabetes underscores the complex interplay between immune signaling, metabolic stress, and cellular identity in shaping islet cell phenotypes in #T1D @bcellorg.bsky.social www.biorxiv.org/content/10.1... @albertadiabetes.bsky.social

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 ...

Multiomic QTL mapping reveals phenotypic complexity of GWAS loci and prioritizes putative causal variants.
www.cell.com/cell-genomic...

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...

High glucose/ChREBP-induced Hif-1α transcriptional activation in CD4+ T cells reduces the risk of #diabetic #kidney disease by inhibiting the Th1 response tinyurl.com/nhhj48sx 🔓

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...

Dear Friends,
Happy to share our new preprint which describes the discovery of a new alpha to beta cell transitional cell type in the human pancreas using singe cell multiomic and genetic lineage tracing. www.biorxiv.org/content/10.1...

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.

β cell dedifferentiation, the underlying mechanism of diabetes in Wolfram syndrome | Science Translational Medicine www.science.org/doi/10.1126/...

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...

Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues | Science www.science.org/doi/10.1126/...

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...

🚨 Excited to share new results! We find that beta cells activate innate immune signaling to adapt to obesity or metabolic stress by promoting both Parkin dependent and independent mitophagy.

Mitophagy FTW! We'd be honored if you gave it a read. 😀
www.biorxiv.org/content/10.1...

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...

#RNaseIII #snoRNA #Spombe

www.biorxiv.org/content/10.1...

MDA5 variants trade antiviral activity for protection from autoimmune disease 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...

MDA5 variants trade antiviral activity for protection from autoimmune disease.
www.medrxiv.org/content/10.1....

Mechanistic insights and approaches for beta cell regeneration - Nature Chemical Biology 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.

Mechanistic insights and approaches for beta cell regeneration.
www.nature.com/articles/s41...