Klaus H. Kaestner

The ortholog of the Human T2D Risk Gene STEAP2 is Required for Glucose Stimulated Insulin Secretion in Mice

This study shows that Steap2 is essential for glucose-stimulated insulin secretion in mice by maintaining mitochondrial function in pancreatic beta-cells.

Utilizing single-cell data for per-cell type eQTL mapping in the human pancreas

This study identifies cell type-specific eQTLs in the human pancreas using single-cell RNA-seq data and deconvoluted bulk RNA-seq data, revealing new genetic signals and associations with metabolic disease.

Human length telomeres restrict the regenerative potential of hematopoietic stem cells in mice

The paper shows that human-length telomeres in mice restrict hematopoietic stem cell regenerative potential under stress conditions.

Spatial transcriptomics from pancreas and local draining lymph node tissue reveals a lymphotoxin-β signature in human type 1 diabetes

This study uses spatial transcriptomics to identify inflammation signatures in pancreas and lymph node tissues of T1D patients, highlighting LTB and other genes involved in disease pathogenesis.

A universal platform for simultaneous TCRα/β removal enables safer and more potent TCR therapies and autoimmune modeling

This paper presents a CRISPR-based platform that removes endogenous TCRα/β chains to enhance transgenic TCR function and safety in T-cell therapies and autoimmune modeling.

Epigenetic adaptation of beta cells across lifespan and disease: age-related demethylation is advanced in type 2 diabetes

The paper examines age-related DNA methylation changes in beta and alpha cells using HPAP data, finding accelerated demethylation in T2D beta cells.

Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1

This study introduces two RTEL1 mouse models with distinct mutations at amino acid 492, showing that M492K affects telomere length while M492I impairs telomere protection, leading to different disease phenotypes.

Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset

The paper analyzes immune cell changes in human pancreas-draining lymphatic tissues before and after T1D onset, identifying proinflammatory patterns and genetic risk correlations.

IFN-α Induces Heterogenous ROS Production in Human β-Cells

This study shows IFN-α induces heterogeneous ROS production in human β-cells, with healthier donors having more ROS-accumulating cells, and identifies enriched immune-related genes in ROS-producing cells.

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

The paper identifies transitional cell states between alpha and beta cells in human islets using single-cell multiome data, suggesting potential for alpha-to-beta transdifferentiation.

G6PC2 controls glucagon secretion by defining the setpoint for glucose in pancreatic α-cells

This study identifies G6PC2's role in regulating glucagon secretion in α-cells, showing it controls glucose setpoint and suggests G6PC2 inhibitors could improve glycemic control.

TNFSF13 insufficiency disrupts human colonic epithelial cell-mediated B cell differentiation

This study investigates the role of TNFSF13 in colonic epithelial cell-B cell interactions and finds that TNFSF13 insufficiency disrupts B cell differentiation and epithelial growth.

Shared and unique chromatin accessibility and 3D functional interactions of substance use disorder loci implicate cell types beyond the brain

This paper identifies shared and unique chromatin accessibility and 3D interactions of SUD loci, implicating non-neural cell types like pancreatic β-cells and showing a causal link between T2D and AUD.

Aberrant TNF signaling in pancreatic lymph nodes of patients with Type 1 Diabetes

This study identifies heightened TNF pathway activity and chromatin remodeling in pancreatic lymph node CD4+ T cells from T1D patients, supporting the use of TNF inhibitors in clinical trials.

AnnoSpat annotates cell types and quantifies cellular arrangements from spatial proteomics

AnnoSpat annotates cell types and quantifies cellular arrangements from spatial proteomics data, showing improved performance over existing methods in diabetic tissue analysis.

Villification of the intestinal epithelium is driven by Foxl1

This study identifies Foxl1 as a key driver of intestinal villification by regulating BMP, PDGFR, and planar cell polarity genes in telocyte progenitors.

Benchmarking algorithms for joint integration of unpaired and paired single-cell RNA-seq and ATAC-seq data

This study benchmarks seven methods for integrating unpaired and paired scRNA-seq and snATAC-seq data, finding that multiome data improve cell type annotation but require sufficient cell numbers.

Telomouse - a mouse model with human-length telomeres generated by a single amino acid change in RTEL1

This paper introduces a mouse model with human-length telomeres by modifying RTEL1 and shows its impact on regenerative capacity.

Modeling Type 1 Diabetes progression from single-cell transcriptomic measurements in human islets

This study uses single-cell transcriptomics and machine learning to predict T1D development in autoantibody-positive donors and identifies shared gene signatures across cell types.

Computational workflow and interactive analysis of single-cell expression profiling of islets generated by the Human Pancreas Analysis Program

The paper presents a computational workflow and interactive tool for analyzing single-cell RNA-seq data from pancreatic islets of diabetic and non-diabetic donors.

Spatially resolved human kidney multi-omics single cell atlas highlights the key role of the fibrotic microenvironment in kidney disease progression

Multi-omic and spatial profiling of 81 human kidney samples resolves four tissue microenvironments; the fibrotic one's gene signature is reported to beat histopathology at predicting outcome.

Adaptation to chronic ER stress enforces pancreatic β-cell plasticity

This study shows chronic ER stress induces β-cell plasticity, but excessive stress leads to identity loss and is linked to T1D progression.

The three-dimensional chromatin structure of the major human pancreatic cell types reveals lineage-specific regulatory architecture of T2D risk

The paper uses 3D chromatin maps to identify cell-type-specific regulatory architecture of type 2 diabetes risk by analyzing pancreatic cell types.

Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry

This study uses imaging mass cytometry to analyze pancreatic cells in T2D patients and controls, revealing changes in islet structure, cell composition, and immune cell infiltration.

Single cell resolution regulatory landscape of the mouse kidney highlights cellular differentiation programs and renal disease targets

The paper maps the regulatory landscape of the mouse kidney at single cell resolution, identifying key transcription factors and regulatory circuits, and linking variants to kidney disease.

Multiomics single-cell analysis of human pancreatic islets reveals novel cellular states in health and type 1 diabetes

Exome-by-phenome-wide rare variant gene burden association with electronic health record phenotypes

This study identifies robust gene-phenotype associations by analyzing rare loss-of-function variants in exome-wide data linked to electronic health records.

Collapse of the hepatic gene regulatory network in the absence of FoxA factors

This study shows that FoxA factors are essential for maintaining the hepatic gene regulatory network in adult mice, as their loss leads to rapid hepatocyte dedifferentiation and lethality.

Discovery of 318 novel loci for type-2 diabetes and related micro- and macrovascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis.

Multi-ethnic type 2 diabetes (T2D) meta-analysis of 228,499 cases and 1,178,783 controls finds 318 previously unreported loci, 804 expression-colocalized genes, and 13 SNP-by-T2D vascular-outcome interactions.

A network of microRNAs acts to promote cell cycle exit and differentiation of human pancreatic endocrine cells

The paper identifies miRNAs that promote cell cycle exit and differentiation of human pancreatic endocrine cells through regulatory networks.