title: Viral Mimicry may Help Explain Immunogenic Cell Death

city: Austin

first: Jonathan

last: Sessler

state: Texas

address: 100 E 24th St, Austin, TX

institute: University of Texas Austin

summary: Viral mimicry may be an underappreciated contributor to chemotherapeutic potency in animal models and patients. This hypothesis is based on studies of a bis-Au(I)-NHC complex that was found to generate a strong anti-tumor immune response in vivo in two different challenge studies using an iKAP colorectal cancer mouse model. RNA profiling of treated cells revealed the stimulation of genes that overlap with those upregulated during a viral infection. The bis-Au(I)-NHC complex generates reactive oxygen species (ROS) through the simultaneous redox cycling of the naphthoquinone moiety and inhibition of thioredoxin reductase (TrxR2) with Au(I). This ROS increase causes endoplasmic reticulum stress, activation of the unfolded protein response pathway and upregulation of Ifih1, a gene that encodes for the viral dsRNA sensor MDA5. Activation of MDA5 triggers a strong type I interferon response and expression of chemokine ligand 10 (CXCL10) that can recruit immune cells to the treated tumor in a manner analogous to immune responses during viral infection. This proposed mechanism bridges the gap between cytotoxicity and the innate and adaptive immune responses. We suggest viral mimicry may be a key driver of chemotherapy potency in animals and an important determinant of positive outcomes in cancer patients.

overall_design: RNA seq profiling of iKAP cells treated with either compound 1, oxaliplatin or auranofin vs  untreated.

last: Levine

first: Jiexi

last: Li

first: Lauren I

last: Ehrlich

middle: A

last: DePinho

first: Brent

last: Iverson

middle: L


title: Immunosuppressive myeloid signaling and distinct malignant cell states in pancreatic neuroendocrine tumors revealed by single-nucleus RNA-seq

status: Public on Feb 18 2026

city: Boston

first: William

last: Hwang

state: Massachusetts

address: 185 Cambridge St

department: Center for Systems Biology

country: USA

institute: Massachusetts General Hospital

type: Expression profiling by high throughput sequencing

summary: Pancreatic neuroendocrine tumors (PNET) are rare and heterogeneous neoplasms with increasing incidence worldwide. Currently, there is no clinically-relevant molecular framework for risk-stratifying patients with PNET. In this study, we used single-nucleus RNA-sequencing to uncover the spectrum of malignant cell states and interactions within the tumor microenvironment.  We uncovered a gene expression program enriched in neural/synaptic signaling genes associated with aggressive clinical behavior, altered telomeres, and broad chromosomal loss of heterozygosity. Moreover, it is associated with worse overall survival in independent cohorts. Another novel malignant cell state was enriched for VEGF-signaling and found to interact with macrophages via glutamate, promoting an immunosuppressive phenotype in macrophages and a more invasive phenotype in malignant cells. This study provides insight into the heterogeneity of malignant cells in PNET, and these diverse cell states and intercellular interactions that may be further explored for prognostication and therapeutic targeting.

overall_design:
We performed single-nucleus RNA sequencing on resected primary and metastatic PNETs (n = 20).

***************************************************************
Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access.
***************************************************************

first: Jeanna

middle: M

last: Arbesfeld-Qiu

first: Jae-Won

last: Cho

first: Jennifer

last: Su

first: Jimmy

last: Guo

first: Hannah

last: Hoffman

first: Carina

last: Shiau

first: Steven

last: Wang

first: Martin

last: Hemberg


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [ChIP-seq mouse, CTCF, SMC1, MED1]

status: Public on Feb 17 2026

first: Kaifu

last: Chen

state: MA

address: 300 Longwood Ave

department: Cardiology

institute: Boston Children's Hospital

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Recent molecular advancements have revolutionized our understanding of the role of three-dimensional (3D) genome organization in gene regulation. Yet, the impact of acute hormonal signaling on reshaping genome structure and its consequences for metabolic processes remain largely unexplored. β3-adrenergic receptor (β3-AR) hormonal signaling is imperative for brown adipose tissue (BAT) thermogenesis. Here, we demonstrate that β3-AR signaling induces rapid reorganization of fine-scale genome architecture in murine and human brown adipocytes within four hours. High-resolution Micro-C profiling reveals dynamic chromatin loop formation associated with activation of thermogenic genes. Mechanistically, β3-AR signaling promotes p18Hamlet/SRCAP complex assembly, catalyzing incorporation of the histone variant H2A.Z into nucleosomes. ATAC-sequencing reveals that H2A.Z enhances chromatin accessibility at loop anchors, supporting loop formation by facilitating the recruitment of looping factors such as the Mediator complex. Disruption of H2A.Z compromises dynamic chromatin looping and transcriptional activation of thermogenic genes in both species. Mice with BAT-specific H2A.Z deficiency exhibit reduced thermogenic activity and impaired glucose tolerance. Revisiting genome-wide association study analysis reveals that H2A.Z-occupied loops are linked to genetic variants associated with obesity and its related metabolic disorders. Together, these findings highlight the rapid adaptability of 3D genome organization to acute β3-AR signaling and its critical role in brown adipocyte thermoregulation.

overall_design: Chromatin immunoprecipitation-sequencing  (ChIP-seq) for CTCF and SMC1 in vehicle-treated control and β3-AR-stimulated control brown adipocytes. ChIP-seq for MED1  in vehicle-treated control, β3-AR-stimulated control, and β3-AR-stimulated H2A.Z knockdowon (KD) brown adipocyte.

first: Yang

last: Zhang

first: Rongbin

last: Zheng

first: Tadataka

last: Tsuji

first: Chih-Hao

first: Xiangyu

last: Liu

first: Yu-Hang

last: Xing

first: Justin

last: Darcy

first: Matthew

middle: D

last: Lynes

first: Morten

last: Lundh

first: Rini

last: Arianti

first: Rui

last: Dong

first: Brice

last: Emanuelli

first: Miguel

middle: N

last: Rivera

first: Endre

last: Kristóf

first: Ronald

last: Kahn

first: Ferenc

last: Győry

first: Yu-Hua

last: Tseng


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [ChIP-seq human]

first: Kaifu

last: Chen

overall_design: Chromatin immunoprecipitation-sequencing  (ChIP-seq) for H3K27ac in vehicle-treated control, FSK-treateed-control primary human brown adipocytes. ChIP-seq for H2A.Z in FSK-treateed-control primary human brown adipocytes.

first: Yang

last: Wang


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [PRO-seq mouse]

overall_design: We performed PRO-seq in mouse.

last: Zhang

first: Rongbin

last: Zheng

first: Tadataka


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [CUT&Run mouse]

overall_design: Cleavage Under Targets & Release Using Nuclease (CUT&RUN) for H2A.Z in unstimulated and β3-AR-stimulated primary murine brown adipocytes to profile H2A.Z genome-wide incorporation.

last: Tsuji

first: Chih-Hao

first: Xiangyu

last: Liu


title: Transcriptomic Profiling of Ferroptosis in Enteric Neurons: Bulk RNA-Seq of IM-FEN Cells Treated with Palmitate

city: Decatur

first: Shanthi

last: Srinivasan

state: Georgia

address: 5A137-1670 Clairmont Rd,

department: Division of Digestive Diseases

institute: Emory University

summary: Palmitic acid (PA), a major component of Western dietary fats, is known to induce ferroptotic cell death in enteric neurons. In this study, we performed bulk RNA-seq on Immortalized Mouse-Fetal Enteric Neurons (IM-FEN) treated with PA (0.5 mM, 24 h) or vehicle control to characterize transcriptional changes associated with ferroptosis. Sequencing was performed using the Illumina NovaSeq 6000 platform. The dataset provides insight into lipid-induced neuronal stress and ferroptosis-relevant signaling networks.

overall_design: IM-FEN cells were treated with palmitic acid (0.5 mM) or vehicle control (10% BSA) for 24 hours. Each condition included six biological replicates (n = 6). Total RNA was extracted and subjected to paired-end sequencing on the Illumina NovaSeq 6000 platform. The study includes 12 raw FASTQ files (paired-end; R1 and R2) and a normalized gene expression matrix. This dataset enables transcriptomic comparison of ferroptosis-associated gene programs induced by lipid overload in enteric neurons.

first: Arun

last: Balasubramaniam

first: Yunshan

first: Francesca

last: Cingolani

first: Simon

last: Mwangi


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [RNA-seq human]

overall_design: We performed RNA-seq in vehicle-treated control, forskolin (FSK)-treated control, and FSK-treated H2A.Z knockdowon primary human brown adipocytes to determine the transcriptional dynamics during thermogenesis and the impact of H2A.Z knockdown on gene activation.

first: Yu-Hang

last: Xing

first: Justin

last: Darcy

first: Matthew

last: Lynes

first: Morten

last: Lundh

first: Rini

last: Arianti

first: Rui

last: Dong

first: Brice

first: C. Ronald


title: The Conserved Non-Coding Sequence CNS11 Is A Master Control Region for Rorc Transcription in Type 17 Immune Cells [4C-Seq]

city: Beijing

first: Hao

address: Haidian  District

country: China

institute: Tsinghua University

summary: As the master transcription factor, RORγt controls the development and function of all type 17 immune cells. Although the trans-regulatory mechanisms governing Rorc expression have been extensively studied, the cis-regulatory mechanisms that differentially regulate Rorc transcription across distinct lymphocytes, particularly in innate lymphocytes, remain largely unknown. Here, we identified CNS11 at the Rorc gene as essential for the development of all type 17 immune cells. Deletion of CNS11 impaired the maintenance but not induction of Th17 cells, abolished the development of RORγt+ Treg cells, RORγt+ γδT cells and RORγt+ antigen-presenting cells, and blocked ILC3 induction from early progenitors, leading to a complete absence of secondary lymphoid organs. Mechanistically, CNS11 mediates the Rorc transcription through a RORγt-dependent feedforward regulatory loop in a cell-type-specific manner. Specifically, the interaction of CNS11 with RORγt and RUNX3 dictated the development of ILC3s, while its interaction with RORγt and/or c-MAF was crucial for RORγt expression in Th17 cells, RORγt+ Treg cells and RORγt+ γδT cells. Our study reveals CNS11 as a key transcription factor binding hub and master control region for Rorc transcription in distinct lymphocytes.

overall_design: 4C experiment of CNS11 in ILC3s isolated from the small intestine lamina propria of Rag1-deficient mice.

first: Ruifeng

last: Li

first: Chen


title: The Conserved Non-Coding Sequence CNS11 Is A Master Control Region for Rorc Transcription in Type 17 Immune Cells [CUT&Tag]

overall_design: CUT&Tag for RUNX3, RORγt and IgG control (rabbit+rat) in ILC3s isolated from the small intestine lamina propria of Rag1-deficient mice.


title: DNA methylation profiling in Huntington’s disease reveals disease associated changes in the striatum

city: Exeter

first: Gregory

last: Wheildon

address: Stocker Road

department: CBS

country: United Kingdom

institute: University of Exeter

type: Methylation profiling by genome tiling array

summary: Huntington’s disease is caused by a trinucleotide CAG repeat expansion in the HTT gene. Despite displaying autosomal dominance, phenotypic variation exists amongst mutation carriers, in particular relating to the age that symptoms first occur. This variation is predominantly driven by an inverse relationship between CAG expansion size and age of symptom onset. However, the majority of variation in age of onset is thought to be driven by environmental influences, independently of CAG repeat length. Since DNA methylation can be altered by environmental factors, and as methylomic variation is reported in other neurodegenerative diseases, it may offer a potential mechanism underlying disease manifestation. Here, we present the first epigenome-wide association study of Huntington’s disease conducted in the striatum, the primary region of neuropathology, along with the entorhinal cortex and cerebellum in 42 individuals (22 control; 20 Huntington’s disease) on the Illumina EPIC v1 array. We identified seven Bonferroni-significant differentially methylated CpGs within the striatum along with 27 differentially methylated regions. Weighted gene correlation network analysis identified six modules of co-methylated CpGs that were associated with Huntington’s disease, with ontological analyses showing enrichment in disease relevant processes. Furthermore, integration of single-nuclei RNA sequencing data highlighted that genes annotated to these modules are enriched in striatal spiny projection neurons, the primary cell types affected in the disease. These results suggest that DNA methylation is altered at loci associated with Huntington’s disease in disease relevant regions and cell types.

overall_design: We aimed to profile DNA methylation in Huntington's disease (HD) brain tissue in order to identify potential contributors to non-gentic driven phenoypic variation in the disease. DNA methylation was quantifed in DNA samples extracted from post-mortem brain tissue, taken from Huntington's disease patients and compared to samples taken from healthy control individuals, using the Infinium Methylation EPIC array version 1. Following quality control measures, 113 samples (striatum = 37; entorhinal cortex = 38; cerebellum 38) from 42 individuals were used to identify differentially methylated postions associated with HD status.

first: G

first: A R

last: Smith

first: L

last: Weymouth

first: J

last: Harvey

first: M

last: Kouhsar

last: Macbean

first: C

last: Troakes

first: E

last: Pishva

first: R G

first: K

last: Lunnon


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [RNA-Seq mouse]

first: Kaifu

last: Chen

summary: β3-adrenergic receptor (β3-AR) hormonal signaling is imperative for adaptative thermogenesis, facilitating heat generation during cold exposure. This study explores how β3-AR signaling regulates thermogenic gene activation by altering the three-dimensional (3D) genome organization. Our findings reveal a rapid 3D genome reorganization in brown adipocytes following 4 hours of β3-AR stimulation, highlighted by high-resolution Micro-C analysis. This reorganization involves substantial dynamic changes in chromatin loops, coupled with activation of genes involved in thermogenesis. Mechanistically, β3-AR signaling promotes the p18Hamlet/SRCAP complex assembly, catalyzing the chromatin incorporation of the histone variant H2A.Z. H2A.Z incorporation enhances chromatin accessibility at loop anchors, facilitating loop formation. Disruption of H2A.Z impairs loop dynamics and thermogenic function of brown adipocytes, with implications for both mice and humans. Notably, human homologous loop anchors are associated with obesity-related genetic variants. This study underscores the critical role of 3D genome architecture in thermogenic regulation, offering new dimensions into obesity’s molecular underpinnings.

overall_design: We performed RNA-seq in vehicle-treated control, β3-AR-stimulated control, and  β3-AR-stimulated H2A.Z knockdowon brown adipocyte to determine the transcriptional dynamics during thermogenesis and the impact of H2A.Z knockdown on gene activation.

first: Yang

last: Zhang

first: Rongbin

last: Zheng

first: Tadataka

last: Tsuji

first: Yu-Hang

first: Chih-Hao

last: Wang

first: Justin

first: Matthew

first: Miguel

last: Rivera

last: Kahn

first: Ferenc

last: Győry

first: Xiangyu

last: Liu

first: Morten

first: Rini

last: Emanuelli

first: Endre

last: Kristóf

first: Yu-Hua

last: Tseng


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [ChIP-Seq mouse, H3K27ac, H3K4me3, H2AZ]

overall_design: Chromatin immunoprecipitation-sequencing  (ChIP-seq) for H3K4me3, H3K27ac, and H2A.Z  in vehicle-treated control, β3-AR-stimulated control, and β3-AR-stimulated H2A.Z knockdowon (KD) brown adipocyte.

last: Xing

last: Darcy

last: Lynes

first: Rui

last: Dong

first: C. Ronald

last: Lundh

last: Arianti

first: Brice


title: Depolymerizing F-actin accelerates the exit from pluripotency to enhance stem cell-derived islet differentiation [scRNA-Seq]

status: Public on Mar 13 2026

city: St. Louis

first: Jeffrey

middle: Robert

last: Millman

state: MO

address: 660 South Euclid

institute: Washington University in St. Louis

summary: In this study, we performed single-cell RNA sequencing and single-nuclei multiomic sequencing (RNA+ATAC) at various stages during the differentiation of human pluripotent stem cells to stem cell-derived islets after treatment with the actin depolymerizing compound latrunculin A (latA) during the first 24 hours of differentiation. We show that depolymerizing F-actin with latA during the first 24 hours of definitive endoderm formation (stage 1) facilitates rapid exit from pluripotency and alters Activin/Nodal, BMP, JNK-JUN, and WNT pathway signaling dynamics. These signaling changes influence downstream patterning of the gut tube, leading to improved pancreatic progenitor identity and decreased expression of markers associated with other endodermal lineages. Continued differentiation generates islets containing a higher percentage of β cells that exhibit improved maturation, insulin secretion, and ability to reverse hyperglycemia. Furthermore, this latA treatment reduces enterochromaffin cells in the final cell population and corrects differentiations from hPSC lines that otherwise fail to consistently produce pancreatic islets, highlighting the importance of cytoskeletal signaling at the onset of directed differentiation.

overall_design: Human pluripotent stem cells were differentiated to stem cell-derived islets (SC-islets). During the first 24 hours of differentiation in stage 1, latA was added to the indicated samples, and these were compared to untreated samples (control). When looking at the effects of latA treatment during stage 1, a range of concentrations were tested (either 0.1uM, 0.175uM, or 1.5uM). For later experiments (stages 3-6), only 0.175uM latA was used. Single-cell RNA sequencing was performed everyday of stage 1, at the start of stages 3, 4, and 5, as well as one week into stage 6.

first: Nathaniel

last: Hogrebe

first: Mason

last: Schmidt

first: Punn

last: Augsornworawat


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [ATAC-Seq mouse]

first: Kaifu

last: Chen

overall_design: We performed ATAC-seq in vehicle-treated control, β3-AR-stimulated control, and  β3-AR-stimulated H2A.Z knockdowon (KD) brown adipocyte to assess chromatin accessibility changes during thermogenesis and the impact of H2A.Z KD on chromatin accessibility.

first: Yang

last: Zhang

first: Rongbin

last: Zheng

first: Tadataka

last: Tsuji

first: Yu-Hang

first: Chih-Hao

last: Wang

last: Rivera

first: C Ronald


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [Micro-C mouse]

overall_design: We performed high-resolution Micro-C in vehicle-treated control, β3-AR-stimulated control, and  β3-AR-stimulated H2A.Z knockdowon (KD) brown adipocyte to assess 3D genome reorganization during thermogenesis and the impact of H2A.Z KD on chromatin loop rewiring.

first: Justin

first: Matthew

first: Miguel

last: Kahn

first: Ferenc

last: Győry

first: Xiangyu

last: Liu

first: Morten

first: Rini

last: Emanuelli

last: Kristóf


title: A molecular map of the human spinal dorsal and ventral horn defines arrangement of neuronal types and glial sex differences

status: Public on Feb 16 2026

city: Dallas

first: Allan-Hermann

last: Pool

state: TX

address: 6000 Harry Hines Blvd

department: Department of Neuroscience, Peter O'Donnell Brain Institute, Department of Anesthesia and Pain Management

institute: University of Texas Southwestern Medical Center

summary: The submitted dataset contains multiomic (single-nucleus RNA-seq and scATAC-seq) data from adult (p56) mouse male and female lumbar spinal cords for cross-species analysis.

overall_design: Lumbar spinal cords were harvested from adult (p56) C57Bl6J male and female mice. Nuclei were extracted and NeuN+ neuronal nuclei were isolated with FACS sorting. Resulting neuronal suspensions were profiled with Chromium Next GEM Single Cell Multiome ATAC + Gene Expression kits from 10x Genomics.

first: Satoshi

last: Ishishita


title: Schizophrenia-linked gene expression changes across cortical layers and cellular microenvironments in human prefrontal cortex [Visium]

city: Baltimore

first: Keri

last: Martinowich

state: Maryland

address: 855 N Wolfe St Suite 300

institute: Lieber Institute for Brain Development

summary: Molecular mechanisms underlying dorsolateral prefrontal cortex (dlPFC) dysfunction in schizophrenia (SCZ) are poorly understood. dlPFC cell types are spatially organized across the six layers into functional microcircuits, which regulate cognitive and emotional processes that are implicated in SCZ. While regional specificity across cortical layers and cell types has been demonstrated for some SCZ-linked genes, spatially-resolved transcriptomics (SRT) can more definitively map molecular associations of disease. We investigated spatial gene expression changes in the human dlPFC from neurotypical control (n=31) and SCZ (n=32) brain donors using the Visium platform with incorporation of immunostaining to label perineuronal nets, neurons and vasculature. SCZ-associated DEGs were then mapped across these labeled cellular microenvironments and cortical layers. Major transcriptional alterations were identified in synaptic and neuroimmune pathways, which we localized to neuropil and glia-enriched domains. Integrative analysis with bulk and single-cell RNA studies highlighted distinct roles for spatially-localized glial cell populations, and identified enrichment of novel DEGs in endothelial cells and microglia. These findings were supported by enrichment of SCZ genetic risk across similar domains, and association of laminae-specific transcription factors to SCZ risk variants. Cellular resolution SRT using Xenium extended laminar disease associations to spatially-organized cell types. The findings highlight unique advantages of SRT to identify novel SCZ-related biology, particularly for cellular populations and compartments that may be missed with alternative technologies. We provide data resources to enable sample-level visualization of the spatial transcriptomics data (Samui) and to explore SCZ-associated DEGs across spatial domains (iSEE-layer adjusted) and cellular microenvironments (iSEE-Neuropil, iSEE-Neuron, iSEE-vasculature, iSEE-PNNs).

overall_design:
The study includes fresh-frozen postmortem human brain tissue sections obtained from the dorsolateral prefrontal cortex (DLPFC) of 32 donors with schizophrenia (SCZ)  and 31 neurotypical controls (NTC). A single 10-µm-thick cryosection per donor was analyzed using the 10x Genomics Visium spatial transcriptomics platform (v1, 3' Gene Expression), yielding a total of 63 samples. The primary comparison was made between diagnostic groups: 32 SCZ samples and 31 NTC samples.

***************************************************************
Raw files for human/patient samples are being made available in dbGaP (https://www.ncbi.nlm.nih.gov/gap/) for controlled access to the personally identifiable sequence data.
***************************************************************

first: Sang-Ho

last: Kwon

first: Boyi

last: Guo

first: Cindy

last: Fang

first: Madhavi

last: Tippani

first: Svitlana

middle: V

last: Bach

first: Ryan

last: Miller

first: Sarah

middle: E

last: Maguire

first: Madeline

middle: R

last: Valentine

first: Seyun

last: Oh

first: Aarti

last: Jajoo

first: Artemis

last: Iatrou

first: Vijetha

last: Balakundi

first: Yufeng

last: Du

first: Annie

middle: B

last: Nguyen

first: Ruth

first: Uma

last: Kaipa

first: Heena

last: Divecha

first: Jashandeep

middle: S

last: Lobana

first: Joel

last: E. Kleinman

first: Nikolaos

middle: P

last: Daskalakis

first: Thomas

last: Hyde

first: Stephanie

middle: C

last: Page

first: Kristen

last: Maynard

last: Hicks


title: Phase separation of heterochromatin protein 1 regulates virulence gene expression in Plasmodium falciparum

city: Pune

first: Krishanpal

last: Karmodiya

state: Maharashtra

address: IISER PUNE, Dr. Homi Bhabha Road, Pashan

country: India

institute: IISER Pune

summary: Malaria caused by Plasmodium falciparum involves antigenic variation on the infected red blood cells through mutually exclusive expression of var genes. The repressed var genes have a distinct genome organization where they localize as a cluster near the nuclear periphery and are bound by PfHP1 (P. falciparum Heterochromatin Protein 1). However, the mode of regulation of var genes by PfHP1 remains unclear. In this study, we show that PfHP1 undergoes liquid-liquid phase separation (LLPS) in vitro in an RNA and DNA-dependent manner. Single-molecule DNA tethering experiments further revealed that AT-rich DNA sequences act as nucleation sites for the assembly and compaction of PfHP1-mediated heterochromatinization. We have also identified point mutations in the IDRs (intrinsically disordered regions) of PfHP1 that disrupt its phase separation as well as DNA compaction in vitro. An ectopic expression of PfHP1 phase separation and DNA compaction mutants led to dispersed nuclear localization, in contrast to the punctate appearance of the wild-type protein and altered chromatin binding at var genes. These results were corroborated with DiCre/loxP based conditional expression of the same PfHP1 mutants, which also led to the de-repression of multiple var genes (as many as 54 out of 60 var genes), mimicking the phenotype of PfHP1 depletion mutants. To assess the dynamic properties of PfHP1 condensates in vivo, we performed fluorescence recovery after photobleaching (FRAP) in live parasites, which revealed rapid fluorescence recovery, supporting their liquid-like behaviour. In conclusion, our study demonstrates the role of PfHP1 mediated LLPS in formation of heterochromatin and var gene silencing; unveiling a fundamental mechanism that drives antigenic variation in P. Falciparum.

overall_design: We performed HiC-seq on PfHP1 mutants to study the effect of its phase separation on genome organization and var gene clustering.

first: Karmodiya

last: Krishanpal

first: D. V.

last: Mamatharani


overall_design: Studying the effect of PfHP1 mutation on virulence genes by RNA sequencing.

first: Mamatharani

last: D. V.


title: Cross-Species Transcriptomic Integration Reveals a Conserved, MIRO1-Mediated Macrophage-to-T Cell Signaling Axis Driving Immunosuppression in Glioma

status: Public on Mar 12 2026

city: Palo Alto

first: Xinnan

last: Wang

state: CA

address: 1201 Welch Road, MSLS Building, Rm P151

department: Neurosurgery

institute: Stanford University

summary: This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Translation in Proximity to Forming Autophagosomes During Sustained Autophagy

status: Public on Feb 12 2026

city: Ottawa

first: Theodore

last: Perkins

state: ON

address: 501 Smyth Rd.

department: Cellular and Molecular Medicine

country: Canada

institute: Ottawa Hospital Research Institute

summary: Autophagy is an evolutionarily conserved catabolic process. In a process requiring a cascade of over 35 autophagy-related genes (Atg), a cupped phagophore membrane expands to surround cytoplasmic material, and seals itself to form an autophagosome, which finally fuses with lysosomes. Large numbers of autophagosomes form during stress responses, while simultaneously cells drastically reduce translation to conserve energy. Here, using proximity-labeling and Fluorescence in situ Hybridization we demonstrate that multiple mRNAs encoding proteins required for autophagy preferentially localize in proximity to forming autophagosomes. Polysome fractionation and proteomics of nascent proteins in proximity to forming autophagosomes provides evidence for the local translation of these mRNAs. Translation and the ribosome-binding protein RACK1 were required for the localization of these mRNAs to forming autophagosomes. Inhibition of translation or knockdown of RACK1 caused depletion of several proteins required for autophagy and a reduction in the number of autophagosomes. Local translation may enable a rapid, energy-efficient supply of proteins for autophagy to enable cells to massively induce autophagy while conserving energy during cell stress.

overall_design: Human cells expressing APEX2 fused to defined subcellular markers were used to identify RNAs proximal to forming autophagosomes. Samples include APEX2-DFCP1 (phagophore), APEX2-LC3B (autophagosome), and control APEX2 constructs (diffuse cytosolic V5 tag or Perilipin). Autophagy was induced by mTOR inhibition (Torin1). Untreated cells serve as non-autophagy controls. Proximity labeling was activated with biotin-phenol and H₂O₂, with -H₂O₂ samples as labeling controls. Biotinylated RNAs were affinity-purified and sequenced. Primary comparisons are DFCP1-APEX2 or LC3B-APEX2 (+H₂O₂) versus matched  -H₂O₂ controls to define proximal RNAs, and DFCP1-APEX2 versus cytosolic or Perilipin APEX2 to identify phagophore-specific enrichment.

first: Yunping

last: Xue

first: Kaela

last: O'Connor

first: Karsten

last: Nalback

first: Alexandre

last: Savard

first: Karen E.

last: King

first: Ryan C.

last: Russel

first: Christain

last: Bahrends

first: Derrick

last: Gibbings


title: Effect of HNF1A-MODY on stem cell islets [II]

status: Public on Feb 11 2026

city: Bergen

first: Lucas

last: Unger

address: Haukelansbakken 15

country: Norway

institute: University of bergen

summary: This project investigates the impact of the hotspot mutation P291fsinsC in HNF1A-MODY (Maturity-Onset Diabetes of the Young) on stem cell-derived islets. RNA sequencing (RNA-seq) was performed on islets differentiated from mutant and control HNF1A-MODY stem cells to study the mutation's effect on gene expression. By comparing the transcriptomic profiles of these islets, the study aims to uncover molecular mechanisms underlying the dysfunction caused by the P291fsinsC mutation during islet development and maturation.

overall_design: HNF1A-MODY stem cells with the P291fsinsC hotspot mutation and wild-type controls were differentiated into the posterior foregut. The Sonic Hedgehog (SHH) pathway was manipulated by removing SANT1 of the differenciation protocol at the start of the stage to assess its effect on the differentiation process and evaluate the impact of the mutation on this developmental stage. Samples where taken at different timpoint along the differentation.

first: Simona

last: Chera


title: Effect of HNF1A-MODY on stem cell islets [S4 bulk rna seq]

overall_design: HNF1A-MODY stem cells with the P291fsinsC hotspot mutation and wild-type controls were differentiated into the endocrine progentor stage.


summary: Malaria caused by Plasmodium falciparum involves antigenic variation on the infected red blood cells through mutually exclusive expression of var genes. The repressed var genes have a distinct genome organization where they localize as a cluster near the nuclear periphery and are bound by PfHP1 (P. falciparum Heterochromatin Protein 1). However, the mode of regulation of var genes by PfHP1 remains unclear. In this study, we show that PfHP1 undergoes liquid-liquid phase separation (LLPS) in vitro in an RNA and DNA-dependent manner. Single-molecule DNA tethering experiments further revealed that AT-rich DNA sequences act as nucleation sites for the assembly and compaction of PfHP1-mediated heterochromatinization. We have also identified point mutations in the IDRs (intrinsically disordered regions) of PfHP1 that disrupt its phase separation as well as DNA compaction in vitro. An ectopic expression of PfHP1 phase separation and DNA compaction mutants led to dispersed nuclear localization, in contrast to the punctate appearance of the wild-type protein and altered chromatin binding at var genes. These results were corroborated with DiCre/loxP based conditional expression of the same PfHP1 mutants, which also led to the de-repression of multiple var genes (as many as 54 out of 60 var genes), mimicking the phenotype of PfHP1 depletion mutants. To assess the dynamic properties of PfHP1 condensates in vivo, we performed fluorescence recovery after photobleaching (FRAP) in live parasites, which revealed rapid fluorescence recovery, supporting their liquid-like behaviour. In conclusion, our study demonstrates the role of PfHP1 mediated LLPS in formation of heterochromatin and var gene silencing; unveiling a fundamental mechanism that drives antigenic variation in P. falciparum.

overall_design: ChIP-seq of PfHP1 and histone modifications in Plasmodium falciparum lines in ring stage. The mutant lines of PfHP1 are also subjected ChIP-seq.

first: D


title: Metabolic Rewiring by Acetate Promotes Efficient Xylose Utilization in Rhodotorula toruloides

status: Public on Feb 07 2026

city: Urbana

first: Christopher

middle: V.

last: Rao

state: IL

address: 600 S Mathews Ave

department: Chemical and Biomolecular Engineering

institute: University of Illinois

summary: To confirm the transcriptional mechanism of xylose gene activation in Rhodotorula toruloides is principally determined by acetate and not other factors, like nitrogen content. RNA-Seq was conducted to understand xylose pathway metabolism. Ultimately, we used new-found understanding in RNA-Seq to engineer R. toruloides better.

overall_design: Nitrogen = {0.1 ammonium sulfate and 0.75 g/L yeast extract, 10 g/L ammonium sulfate}, acetate = {0 g/L, 2 g/L}, time = {48 hr, 64 hr, 88 hr}

first: Joshua

last: Ye

first: Sujit

last: Jagtap

first: Hyun

middle: G

last: Koh

first: Thanh

middle: Q

last: Pham

first: Yong

last: Jin

first: Chris

first: Diya

last: Kamath


title: Analysis of peripheral blood transcript and protein expression across adult systemic lupus erythematosus (SLE) and adult dermatomyositis (DM) patients, each compared to respective healthy matched control subjects.

status: Public on Feb 06 2026

city: Durham

first: James

last: Ward

state: NC

address: 111 TW Alexander Dr

department: Integrative Bioinformatics

institute: NIEHS

summary:
The study interrogates SLE and DM gene expression measurements across three platforms: Affymetrix transcriptomics, SomaLogic proteomics, and Rules Based Medicine (RBM) proteomics. Patients are matched 1:1 with healthy donor subjects by age, ethnicity, and sex. DM patients are matched 1:3 with SLE patients by the same criteria. All patients have been treated for at least one year, and represent patients receiving standard treatment care for the respective diseases. The data posted contain SLE patients in support of the paper Distinct Interferon and Intracellular Signaling Signatures in Systemic Lupus Erythematosus and Dermatomyositis by Integrative Transcriptomic and Proteomic Analysis.
Dermatomyositis (DM) patient consent requires controlled access, as a result the equivalent DM data are deposited in dbGaP Study Accession phs003270.v1.p1.

overall_design: Affymetrix transcriptomics data are provided for 41 SLE patients and 41 SLE_Control matched healthy controls. SomaLogic SOMAscan proteomics array data are provided for 34 SLE patients, 34 matched healthy controls. Rules Based Medicine (RBM) proteomics array data are provided for 34 SLE patients, and 34 matched healthy controls, using the same 34 samples as with SomaLogic proteomics data.

first: Mythri

last: Ambatipudi

first: Zerai

last: Manna

first: Adam

last: Schiffenbauer

first: Michael

last: Smith

first: Saifur

last: Rahman

first: Frederick

middle: W

last: Miller

first: Mariana

middle: J

last: Kaplan

first: Jian-Liang

last: Li

first: Kerry

last: Casey

first: Sarfaraz

last: Hasni

first: Lisa

last: Rider


title: Aryl hydrocarbon receptor restricts axon regeneration of DRG neurons in response to injury [DRG_AN00024583]

status: Public on Feb 05 2026

city: New York

first: Molly

last: Estill

state: NY

address: 1 Gustave L. Levy Place

department: Neuroscience

institute: Mount Sinai School of Medicine

summary: Injured neurons sense environmental cues to balance neural protection and axon regeneration, but the mechanisms are unclear. Here, we unveil aryl hydrocarbon receptor (AhR), a ligand-activated bHLH-PAS transcription factor, as a molecular sensor and key regulator of acute stress response at the expense of axon regeneration. We demonstrated responsiveness of DRG sensory neurons to AhR signaling, which functions to inhibit axon regeneration. Conditional neuronal Ahr deletion accelerated axon regeneration after sciatic nerve injury. Ahr deletion partially mimics the conditioning lesion in priming DRG to initiate axonogenesis gene programs; upon peripheral axotomy, Ahr ablation suppressed inflammation and stress signaling while augmenting pro-growth pathways. Moreover, comparative transcriptomics revealed signaling interactions between AhR and HIF-1α, two structurally related bHLH-PAS α units that share the dimerization partner Arnt/HIF-1β. Functional assays showed that the growth advantage of AhR-deficient DRG neurons requires HIF-1α; but in the absence of Arnt, DRG neurons can still mount a regenerative response. We further unveiled a link between bHLH-PAS transcription factors and DNA hydroxymethylation in response to peripheral axotomy, while RNA-seq of DRG neurons and neuronal single cell RNA-seq analysis revealed a link of AhR regulon to RNA regulation and integrated stress response (ISR), impacting global translation. Altogether, AhR activation favors stress coping and inflammation at the expense of axon regeneration; targeting AhR has the potential to enhance nerve repair.

overall_design: Ahr cKO (Ahr fl/fl Thy1CRE-ERT2/EYFP) or control (Ahr f/f or  f/+) male mice were injected with tamoxifen (once daily, 100 mg/kg i.p. for 5 consecutive days) at 17 weeks of age.  L4-L6 DRGs, both contralateral and ipsilateral were isolated from n=5 mice per group (DRGs from each mouse represents 1 sample) at 4 weeks post-tamoxifen treament. For the injury group, sciatic nerve transection lesion was performed on n=5 mice per group at 4 weeks post-tamoxifen treament and L4-L6 DRGs were isolated 1 day later.  DRGs were dissociated between ZT2 to 4 (ZT=0 when the light turns on in the mouse room).

first: Yiqun

last: Wang

first: Dalia

last: Halawani

first: Arthur

last: Sefiani

first: Aarthi

last: Ramakrishnan

first: Jiaxi

first: Haofei

last: Ni

first: Daniel

last: Halperin

first: Li

last: Shen

first: Cedric

last: Geoffroy

first: Roland

middle: H

last: Friedel

first: Hongyan

last: Zou


title: Engineered Living Systems with Self-Organizing Neural Networks: From Anatomy to Behavior and Gene Expression

first: Haleh

last: Fotowat

address: 201 Brookline Ave

institute: Wyss Institute

summary: A great deal is known about the formation and architecture of biological neural networks in animal models, which have arrived at their current structure-function relationship through evolution by natural selection. Little is known about the development of such structure-function relationships in a scenario where neurons are allowed to grow within evolutionarily-novel, motile bodies. Previous work showed that ectodermal tissue excised from Xenopus embryos, develops into a three-dimensional (3D) mucociliary epidermal organoid ex vivo and exhibits movements distinct from age-matched tadpoles. These ‘biobots’ are autonomous, self-powered, and able to move through aqueous environments. Here we report a new type of biobot, the neurobot, composed of mucociliary epidermis and neural tissue. We show that neural precursor cells implanted in explanted Xenopus ectodermal tissue develop into mature neurons, extending processes both towards the surface and among each other. These self-organized neurobots exhibit unique morphology, more complex movements, and different responses to neuroactive drugs compared to non-neuronal counterparts. Calcium imaging confirms neuronal activity in neurobots. Transcriptomics reveals increased transcript variability, expression of genes related to nervous system development, a shift toward ancient genes, and up-regulation of neuronal genes linked to visual perception.

overall_design: These experiments were aimed to compare gene expression between various types of biological robots constructed out of ectodermal cells of Xenopus laevis. Biobots (XB1-4), are composed of xenopus epidermal cells, where as neurobots (NB1-4) are composed of epidermis as well as neurons derived from ectodermal cells, and sham neurobots (NN1-4) are built similar to neurobots, without the steps for neural differentiation (n=4).

first: Laurie

last: O'Neill

first: Leo

last: Pio-Lopez

first: Megan

middle: M

last: Sperry

first: Patrick

last: Erickson

first: Tiffany

last: Lin

first: Michael

last: Levin


title: Characterization of esophageal squamous cell carcinoma cell lines sensitivity to Palbociclib

status: Public on Feb 02 2026

city: Brussels

first: Xavier

last: Bisteau

address: Route de Lennik 808

country: Belgium

institute: Université Libre de Bruxelles

summary:
Background: Esophageal squamous cell carcinoma (eSCC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. Although immune checkpoint inhibitors such as nivolumab, have shown clinical benefit, particularly in patients with high PD-L1 expression, this subgroup represents only a small fraction of eSCC cases. CDK4/6 inhibitors such as palbociclib have only been tested as second-line agents in eSCC, often in combination with EGFR inhibitors, with minimal benefit.
Methods: Our study evaluates palbociclib as a first-line therapy in treatment-naive eSCC models. Using a panel of 22 eSCC cell lines with integrated multi-omics and phenotypic assays.
Results: We identified three response subtypes, resistant, delayed and arrested, correlated to Rb-pathway status. Interestingly, in delayed responders, palbociclib induced replication stress, DNA damage, and unprotected micronuclei enriched for cGAS, triggering activation of interferon-stimulated genes. Consistent with this, palbociclib enhanced immune cell infiltration in delayed eSCC spheroids within a preclinical vascularized 3D microfluidic system.
Conclusions: Our study demonstrates that first-line palbociclib treatment unmasks intrinsic vulnerabilities in the CDK4/6-Rb axis and triggers innate immune activation in molecularly defined eSCC. Using a translationally relevant 3D vascularized microfluidic system, we provide evidence that early CDK4/6 inhibition not only stall cancer cell growth but also promotes immune cells recruitment. In conclusion, our study identifies palbociclib as a viable first-line therapeutic candidate in selected eSCC patients and uncover its immunomodulatory potential. These findings support further research into CDK4/6 inhibition as first-line treatment for eSCC and highlight its potential to influence the tumor immune microenvironment in ways that could improve responses to combination therapies.

overall_design:
We analyzed 22 human esophageal squamous cell carcinoma cell lines to investigate transcriptional responses to CDK4/6 inhibition. The cell lines used in this study were: TE-1, TE-4, TE-5, TE-6, TE-8, TE-9, TE-10, TE-11, TE-14, TE-15, KYSE-30, KYSE-70, KYSE-140, KYSE-150, KYSE-180, KYSE-270, KYSE-410, KYSE-450, KYSE-510, KYSE-520, COLO-680N, ECGI10
Each cell line was cultured under standard conditions and treated with either DMSO (vehicle control) or 1 μM palbociclib for 6 days. Total RNA was extracted at the end of treatment, and bulk RNA-seq was performed. For each condition, experiments were conducted in biological duplicate.

first: Fabiana

last: Moresi


title: Sex differences in Yap1 oncogene function in immune evasion

city: Houston

first: Nourhan

last: Abdelfattah

address: 6670 Bertner Avenue, HMRI R11-330.17

institute: Houston Methodist Research Institute


title: TFIIB

status: Public on Feb 04 2026

city: Berkeley

first: Britt

last: Glaunsinger

state: California

address: RM 565, 1951 Oxford St

department: PMB

institute: University of California, Berkeley


title: Optimized Protocol for Culturing Porcine Retinal Explants and RNA Isolation

city: Biberach

first: Siavash

last: Khosravi

address: Birkendorfer Strasse 65

country: Germany

institute: Boehringer Ingelheim

summary: The culture of porcine retinal explants serves as a valuable cellular model for studying retinal pathologies and their underlying molecular mechanisms. This protocol provides a detailed, step-by-step guide for dissecting the eye, isolating retina, and culturing primary porcine retinal explants for extended periods. Additionally, we outline procedures for RNA isolation and sequencing from cultured retinal explants, enabling molecular analysis of retinal biology.

overall_design: RNA-seq proifle of organotypic culture of retina from sus scrofa for a dutation of 10 days

first: siavash

last: khosravi

first: Nina

last: Zipple


title: Sex differences in Yap1 oncogene function in immune evasion [P8_Bulk RNA-seq]

summary: The incidence of many human cancers differs according to sex, but little is known about the interplay between oncogenic events and sex as a variable in tumorigenesis. Here we report that the oncogene Yap1 is sexually dimorphic in medulloblastoma progression and immune suppression. We show that Yap1 promotes stemness and blocks differentiation in sonic hedgehog (SHH)-subtype medulloblastoma by at least two distinct but complementary molecular mechanisms to regulate the RNA expression and protein functions of Sox2, Atoh1, NeuroD1, and Zic1/2. Yap1 also promotes an immune suppressive tumor microenvironment by directly regulating Csf1, Igf1, and Igfbp3 transcription and modulating IL6-JAK-STAT3, TNFR1, TGF-β, and CCL5 immune pathways. Notably, Yap1 function is more critical in males and this is evolutionarily conserved: genes downstream of YAP1 identified in mouse models stratify male but not female medulloblastoma patient survival. In summary, we demonstrate a sex-based function for an oncogene, underscoring the critical need to incorporate sex as a variable in cancer mechanism and clinical response studies, particularly those involving YAP1

overall_design: Comparative gene expression profiling analysis of RNA-seq data for fSMO-M2;hGFAPcre (SG), non rescured   fYap1;fSMO-M2;hGFAPcre (YSGnr)  and rescued  fYap1;fSMO-M2;hGFAPcre (YSGr) at P8/P9 after birth

first: Kyuson

last: Yun


title: Genome-scale perturb-seq in primary human CD4+ T cells reveals genes regulating T cell programs and human immune traits.

first: Lattice

last: Data Coordination

address: 3165 Porter Drive

department: Genetics

summary: CD4+ T cells orchestrate immune responses against infection and cancer, yet a comprehensive map of their gene regulatory networks has been lacking. Perturb-seq enables systematic mapping of such networks, but large-scale application in primary human T cells has been challenging. Here, we developed a scalable, probe-based Perturb-seq platform and performed genome-scale perturbations of all expressed genes across 22 million primary CD4+ T cells from four donors under three stimulation conditions. We demonstrate the utility of this dataset in three ways. First, we identify previously unrecognized regulators of the two important immune cytokines, IL-10 and IL-21. Second, we show that ex vivo perturbation signatures can model T cell states observed in population-scale atlases, revealing regulators of helper T cell polarization and T cell aging. Third, we leverage regulatory relationships to mechanistically explain gene–trait associations in immune-related diseases, nominating genes for uncharacterized immune functions. Thus genome-scale perturb-seq in primary human T cells provides a foundational resource for decoding immune variation in humans and reprogramming T cell states for next-generation precision therapies.

overall_design:
scRNA-seq of human CD4-positive, alpha-beta T cells with genome-wide CRISPR interference screen, resting and stimulated conditions from 4 donors.scRNA-seq of human CD4-positive, alpha-beta T cells with genome-wide CRISPR interference screen, resting and stimulated conditions from 4 donors.
bulk RNA-seq of human CD4-positive, alpha-beta T cells with CRISPR interference and T cell stimulation, 5 donors, 9 CRISPRi targets.

UPDATE: [May-27-2026] The following files were updated:
GSE314342_Donor5_bulkRNAseq.csv.gz
GSE314342_Donor6_bulkRNAseq.csv.gz
GSE314342_Donor7_bulkRNAseq.csv.gz
GSE314342_Donor8_bulkRNAseq.csv.gz

bulk RNA-seq of human CD4-positive, alpha-beta T cells with CRISPR interference and T cell stimulation, 7 donors, 9 CRISPRi targets, batches Diff087 and Diff092

bulk RNA-seq of human CD4-positive, alpha-beta T cells with CRISPR interference and T cell stimulation, 3 donors, 9 CRISPRi targets and non-targeting control, 2 stimulation conditions (8 hr and 48 hr restimulation), 2 replicates, batch Diff092

bulk RNA-seq of human CD4-positive, alpha-beta T cells with CRISPR interference and T cell stimulation under Th1, Th2, and nonpolarized culture conditions, 9 donors, 21 CRISPRi gRNAs (18 target genes + 3 non-targeting controls), 3 batches (Diff081, Diff084, Diff089)

first: Ronghui

last: Zhu

first: Emma

last: Dann

first: Jun

last: Yan

first: Justine

last: Reyes Retana

first: Ryunosuke

last: Goto

first: Reese

last: Guitche

first: Lillian

middle: K

last: Petersen

first: Mineto

last: Ota

first: Brian

last: Shy

first: Jonathan

last: Pritchard

first: Alexander

last: Marson


title: Sex differences in Yap1 oncogene function in immune evasion [EndPoint_Bulk RNA-seq]

first: Nourhan

last: Abdelfattah

overall_design: Comparative gene expression profiling analysis of RNA-seq data for fSMO-M2;hGFAPcre (SG)  and rescued  fYap1;fSMO-M2;hGFAPcre (YSGr) at end point


title: Sex differences in Yap1 oncogene function in immune evasion [ChIP-seq]

overall_design: YAP1 ChIPseq data from male and female  fSMO-M2;hGFAPcre (SG) tumors


title: Sex differences in Yap1 oncogene function in immune evasion [scRNA-seq]

overall_design: Comparative scRNA-seq data for fSMO-M2;hGFAPcre (SG)  and rescued  fYap1;fSMO-M2;hGFAPcre (YSGr) males and females at end point


title: Innate tissue immunosurveillance by γδ T cells has real-time dependence on the T cell receptor [RNA-seq]

status: Public on Jan 21 2026

city: London

first: Probir

last: Chakravarty

address: 1Midland Road

institute: Francis Crick

summary: With clonotypic potential to engage different ligands, T cell receptor (TCR) γδ fulfils a key tenet of adaptive immunity. Nonetheless, many γδ repertoires are non-circulating, display limited diversity, and are commonly classified as innate-like, questioning any requirement for the TCR beyond the cells’ development. Addressing this long-standing issue, we now show that the steady-state phenotypes of different tissue-intrinsic γδ T cell compartments share a dependence on constitutive TCR expression.  Deprived of this, cells rapidly become dysregulated, losing their capacity to respond to wide-ranging tissue insults, including imiquimod, an innate inducer of psoriasis-like pathology, u.v. irradiation, and melanoma. Thus, beyond any developmental requirements, the TCR is required in real time to regulate the cells’ innate-like tissue immunosurveillance. Biologically, this clearly distinguishes intrinsic γδ T cells from NK and other innate lymphoid cells, while clinically it stresses the importance of the TCR in delivering gd T cell-based immunotherapies.

overall_design:
Genetic deletion of TCRγδ specifically in tissue-resident γδ T cells was achieved in Cγ1fl/fl mice in vivo by tamoxifen-inducible TCRδ-CreERT2 for skin or Rosa26-CreERT2 for gut.
TCRγδ-deficient (KO) tissue-resident γδ T cells were purified from mouse epidermis, dermis and small intestine. TCR competent (WT) tissue-resident γδ T cells were identically purified as controls. Between 3 to 5 mice per genotype were analyzed per tissue. Each sample came from a individual mouse and corresponds to a biological replicate.
Transcriptomic analysis of TCRγδ KO cells was performed with RNA-seq data to determine gene expression signatures for each set of tissue-specific cells.

first: Miguel

last: Munoz-Ruiz

first: Nicolas

last: Veland

first: Adrian

last: Hayday


title: Mouse Offspring Conceived by In Vitro Fertilization Exhibit Accelerated Reproductive Aging Through Early Ovarian Failure

status: Public on Jan 29 2026

city: Philadelphia

first: Eric

middle: Alejandro

last: Rhon Calderon

state: Pennsylvania

address: 3400 Civic Center Blvd, Bldg 421, Floor 9-175

department: Cell and Developmental Biology

institute: University of Pennsylvania

summary: In vitro fertilization (IVF) is an assisted reproductive technology that has enabled millions of births. Although considered safe, emerging evidence suggests that IVF may have long-term health adverse outcomes in offspring, though its impact on female reproduction, especially on reproductive aging is largely unknown. Here, we use a mouse model to investigate how IVF influences female reproductive and transgenerational health outcomes. We assessed IVF-conceived fetal (E18.5) and adult (12-week and 39-week) female offspring, identifying alterations in ovarian-to-body weight ratios, ovarian morphology, serum sex hormone levels, and transcriptomic and DNA methylation profiles in ovaries, oocytes, and cumulus cells, consistent with biomarkers of accelerated reproductive aging. The offspring of IVF females and wild-type males exhibited altered fetal-to-placental weight ratios, placental morphology, and dysregulated placental gene expression. At 12-weeks-of-age, offspring showed increased body weight, disrupted lipid and glucose metabolism, and transcriptomic and epigenetic changes in liver and reproductive organs. Our results highlight the need for deeper mechanistic understanding of assisted reproduction’s long-term and multigenerational impacts on female reproductive health.

overall_design:
Gene expression analysis using Total RNA extracted from F1: E18.5 ovaries (n=10, Natural=4 and IVF=6), 12 weeks ovaries (n=10, Natural=5 and IVF=5), 39 weeks ovaries (n=10, Natural=4 and IVF=6), 12 weeks single oocytes (n=75, Natural=30 and IVF=45), 39 weeks single oocytes (n=20, Natural=10 and IVF=10), 12 weeks cumulus cells (n=10, Natural=5 and IVF=5), 39 weeks cumulus cells (n=4, Natural=2 and IVF=2) and embryonic day 13.5 female gonads (n=9, Natural=4 and IVF=5).

Please note that the records have been updated on May 28, 2026.

middle: A

last: Rhon-Calderon

first: Cassidy

middle: N

last: Hemphill

first: Alexandra

last: Savage

first: Christopher

last: Krapp

first: Zhengfeng

last: Liu

first: Laren

last: Riesche

first: Richard

last: Schultz

first: Marisa

last: Bartolomei


title: Lung gene expression in WT and estrogen receptor alpha and beta knockout mice exposed to house dust mites

status: Public on Feb 01 2026

city: Bloomington

first: Patricia

last: Silveyra

email: psilveyr@iu.edu, ptrcslvr@gmail.com

state: Indiana

department: Environmental and Occupational Health

institute: Indiana University Bloomington

summary: Sex differences in asthma severity suggest that estrogen signaling plays a key regulatory role in airway inflammation and remodeling, yet the specific contribution of estrogen receptors (ERα and ERβ) remains poorly defined. Here, we investigated how ERα and ERβ shapes physiological, structural, and immunological responses to chronic allergen exposure by examining wild-type (WT), ERα knockout (Esr1⁻/⁻) and ERβ knockout (Esr2⁻/⁻) male and female mice subjected to 5-weeks of house dust mite (HDM) challenge.

overall_design: RNAseq profiling of whole lung tissue from WT, Esr1 knockout and Esr2 knockout mice exposed to house dust mites or PBS for 5 weeks

first: Carolyn

middle: D

last: Ekpruke


title: Mutated fibroblast growth factor receptor 1 is an oncogenic driver and therapeutic target in high-risk neuroblastoma

status: Public on Jan 28 2026

city: Cologne

first: Matthias

last: Fischer

address: Kerpener Str. 62

department: Department of Experimental Pediatric Oncology

institute: University Children’s Hospital of Cologne

summary: Fibroblast growth factor receptor 1 (FGFR1) is recurrently mutated at p.N546 in neuroblastoma. We here sought to examine whether mutant FGFR1 is an oncogenic driver, a predictive biomarker, and an actionable vulnerability in this malignancy. FGFR1 mutations at p.N546 were associated with high-risk disease and rapid tumor progression, resulting in dismal outcome of neuroblastoma patients bearing this alteration. Ectopic expression of FGFR1N546K induced constitutive down-stream signaling and interleukin-3-independent growth in Ba/F3 cells, indicating oncogene addicted proliferation. In FGFR1N546K;MYCN transgenic mice, neuroblastoma developed within the first days of life with fatal outcome within 3 weeks, reflecting the devastating clinical phenotypes of FGFR1 mutant high-risk neuroblastoma patients. Treatment with FGFR inhibitors impaired proliferation and pathway activation in FGFR1N546K-expressing Ba/F3 and patient-derived FGFR1N546K mutant neuroblastoma cells, and inhibited tumor growth in FGFR1N546K;MYCN transgenic mice and in a chemotherapy-resistant patient-derived xenograft mouse model. In addition, partial regression of FGFR1N546K mutant tumor lesions occurred upon treatment with the FGFR inhibitor futibatinib and low-intensity chemotherapy in a patient with refractory neuroblastoma. Together, our data demonstrate that FGFR1N546K is a strong oncogenic driver in neuroblastoma that is associated with failure of current standard chemotherapy, and suggest potential clinical benefit of FGFR-directed therapies in FGFR1 mutant high-risk patients.

overall_design: RNA-seq and gene expression analysis of 8 FGFR1N546K and 11 FGFR1N546K;MYCN transgenic mice. RNA-seq data of the mice transgenic for ALKF1174L;MYCN are available under GSE254751.

first: Lisa

last: Werr


title: Innate tissue immunosurveillance by γδ T cells has real-time dependence on the T cell receptor [ATAC-seq]

last: Chakravarty

overall_design:
Genetic deletion of TCRγδ specifically in tissue-resident γδ T cells was achieved in Cγ1fl/fl mice in vivo by tamoxifen-inducible TCRδ-CreERT2 for skin or Rosa26-CreERT2 for gut.
TCRγδ-deficient (KO) tissue-resident γδ T cells were purified from mouse epidermis, dermis and small intestine. TCR competent (WT) tissue-resident γδ T cells were identically purified as controls. Between 3 to 5 mice per genotype were analyzed per tissue. Each sample came from a individual mouse and corresponds to a biological replicate.
Chromatin accesibility analysis of TCRγδ KO cells was performed with ATAC-seq data to determine differences in chromatin landscape for each set of tissue-specific cells.


title: Hypothyroidism Reduces Myogenic Diversity and Impairs Skeletal Muscle Regeneration After Injury by Altering Myogenic and Non-Myogenic Pathways

status: Public on Jan 20 2026

city: Los Angeles

first: Paola

last: Aguiari

address: 4650 W Sunset Blvd

institute: Children's Hospital, Los Angeles

summary: Thyroid hormone signaling is an essential regulator of skeletal muscle development, function, and metabolism, yet the specific signaling pathways required for muscle regeneration are not yet defined. We utilized scRNA-seq and a cell cycle reporter mouse model (FUCCI, Fluorescent Ubiquitination-based Cell Cycle Indicator) to examine how hypothyroidism impacts repair processes after cardiotoxin-induced injury in mice. During regeneration, and up to 2 months after injury, hypothyroid muscles displayed smaller myofibers and a shift to slower oxidative fiber types.scRNA-seq of tibialis anterior muscle during regeneration revealed that hypothyroidism reduces myogenic lineage diversity. Cell cycle analysis confirmed delayed cell cycle progression at 5 and14 days after injury, with skeletal muscle stem cells stalled at the G1/S transition, hindering differentiation. Transcriptomic data revealed altered non-myogenic dynamics, including elevatedactivated fibro-adipogenic progenitors (FAPs) early in repair and persistent pro-inflammatory macrophages. Integrative regulon and ligand-receptor analysis further demonstrated that T3 acts through dual modes: a direct transcriptional control of myogenic cell cycle and oxidative programs and an indirect paracrine remodeling mediated by FAP and immune signaling networks. This study identifies novel effects of hypothyroidism on myogenic heterogeneity and reduced tissue repair, offering insights into muscle-wasting mechanisms relevant to hypothyroidism-associated myopathy and sarcopenia.

overall_design: scRNA profiling of Tibialis Anterior (TA) muscle cells from euthyroid (Control) and hypothyroid mice, at day 0 (NI, non-injured), day 5, and day 14 after cardiotoxin-induced injury.

first: Laura

last: Perin

first: Anna

last: Milanesi


title: MRTFA-SRF driven gene expression promotes cellular stiffness by controlling cytoplasmic Ca2+ and K+ levels in cancer cells II

city: CHICAGO

first: Ekrem Emrah

last: Er

address: 909 S  WOLCOTT AVE

department: Physiology and Biophysics

institute: The University of Illinois at Chicago

summary: Cellular stiffness, the inverse of compliance, is a biophysical property of cells that fundamentally impacts homeostatic functions and pathological states and understanding how these properties are controlled can provide novel insights into tissue homeostasis and disease mechanisms. A prominent regulator of cellular stiffness is the filamentous actin (F-actin) cytoskeleton that forms aligned stress fibers during cellular contraction. It has been recently shown that F-actin polymerization and the subsequent cortical stiffening of cancer cells is regulated by the myocardin-related transcription factor A (MRTFA) and this results in dramatic changes in the ability of cancer cells to evade anti-tumor immune surveillance. However, the precise mechanism by which MRTFA regulated cortical stiffness remained unknown. Here, we demonstrate that cancer cell stiffening occurs as a consequence of MRTFA binding to its cofactor serum response factor (SRF). Specifically, MRTFA-SRF promotes the expression of Ca2+ and K+ handling genes and the flux of these ions are critically needed for cortical stiffening. Finally, we show the results of a series of rigorous gain-of-function and loss-of-function studies that reveal the large conductance K+ channel auxiliary subunit, KCNMB1, as an MRTFA-SRF target that regulates cell stiffness and F-actin organization. Collectively, these findings point to previously unrecognized MRTFA-SRF targets in cellular stiffness, including a novel druggable ion channel. Here, we test the efficacy of 2 BK channel activators (NS,BMS) under high K+ conditions and how they may affect cancer cell transcriptional changes.

overall_design: 150k AT-3 or E0771 cells were seeded for 24hr in a 6well dish, then treated with the listed treatments for 24hr. RNA was then extracted and submitted for sequencing.

first: Alexa

last: Gajda

first: Mark

last: Sanborn

first: Ekrem

middle: E


title: MRTFA-SRF driven gene expression promotes cellular stiffness by controlling cytoplasmic Ca2+ and K+ levels in cancer cells

status: Public on Jan 19 2026

summary: Cellular stiffness, the inverse of compliance, is a biophysical property of cells that fundamentally impacts homeostatic functions and pathological states and understanding how these properties are controlled can provide novel insights into tissue homeostasis and disease mechanisms. A prominent regulator of cellular stiffness is the filamentous actin (F-actin) cytoskeleton that forms aligned stress fibers during cellular contraction. It has been recently shown that F-actin polymerization and the subsequent cortical stiffening of cancer cells is regulated by the myocardin-related transcription factor A (MRTFA) and this results in dramatic changes in the ability of cancer cells to evade anti-tumor immune surveillance. However, the precise mechanism by which MRTFA regulated cortical stiffness remained unknown. Here, we demonstrate that cancer cell stiffening occurs as a consequence of MRTFA binding to its cofactor serum response factor (SRF). Specifically, MRTFA-SRF promotes the expression of Ca2+ and K+ handling genes and the flux of these ions are critically needed for cortical stiffening. Finally, we show the results of a series of rigorous gain-of-function and loss-of-function studies that reveal the large conductance K+ channel auxiliary subunit, KCNMB1, as an MRTFA-SRF target that regulates cell stiffness and F-actin organization. Collectively, these findings point to previously unrecognized MRTFA-SRF targets in cellular stiffness, including a novel druggable ion channel.

overall_design: To investigate the role of MRTFA-SRF binding on cancer cell stiffness phenotypes, using 2 cell lines with doxycycline-inducible overexpression of wildtype MRTFA or SRF-binding deficient MRTFA (Y238A), data is from 3 separate replicate sets.


title: Epigenetic Silencing of LTR12C family in OCI-AML3

status: Public on Jan 16 2026

first: Ozgen

last: Deniz

state: Greater London

address: Charterhouse square

institute: Barts Cancer Institute

summary: Chromatin accessibility at LTR12C family  has been shown to b required  to maintain stemness properties in leukemic stem cells. Here using CRISPRi epigenetic silencing strategy, we targetted LTR12C family in OCI-AML3 cell line. Our ATAC-seq and CUT&RUN data demonstrate efficient targeting and silencing of entire family using only 4 sgRNAs. Epigenetic silencing of this family leads to slower growth in targeted OCI-AML3 cells compared to control cells.

overall_design: ATAC-seq and cut&run (H3K27ac and H3K9me3) in OCI-AML3 cells transduced with dCas9-KRAB and empty sgRNA vector or LTR12C sgRNA vector.

first: Bryce

last: Drylie

first: Özgen


title: Cohesin cofactor dosage sets the rate of loop extrusion, rendering genome folding tunable yet vulnerable to genetic disruption

status: Public on Jan 08 2026

city: San Francisco

first: Elphege

last: Nora

address: 555 Mission Bay Boulevard South

department: Cardiovascular Research Institute

institute: University of California San Francisco

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series

first: Rini

last: Shah

first: Elphège


title: Protocol for massively parallel RNA assay coupled with immunoprecipitation (MPRNA-IP)

status: Public on Jan 12 2026

city: Baltimore

first: Taeyoung

last: Hwang

state: MD

address: 855 N. Wolfe St, 3rd floor, Suite 300

institute: Lieber Institute for Brain Development

summary: RNA mediates many cellular functions through interactions with RNA-binding proteins (RBPs), and defining the molecular principles underlying these interactions is essential for understanding RNA biology. Here, we describe a detailed protocol for MPRNA-IP, a Massively Parallel RNA assay coupled with ImmunoPrecipitation that enables high-throughput dissection of RNA–protein interactions in cells. This protocol provides a complete experimental and computational workflow, including the design of RNA tiles, large-scale oligonucleotide cloning, mammalian cell transfection, immunoprecipitation of RNA–protein complexes, sequencing library preparation, and downstream data analysis. As an example application, we synthesized a pool of oligonucleotides tiling six lncRNAs and studied PUM2-binding motifs. Together, these procedures allow high-throughput interrogation of RNA sequences to detect sequence and structural elements that contribute to protein binding. For further information on the development and applications of MPRNA-IP, see Lee et al., Nucleic Acids Research, 2024 (https://doi.org/10.1093/nar/gkae334).

overall_design:
Overexpress a pool of oligonucleotides and perform immunoprecipitation in three biological replicates

UPDATE: [Apr-20-2026] GSE315146_GEO_count.csv was replaced with GSE315146_TestPool_count_updated.csv.

first: Yu Hsuan

last: Lee


title: Transposable Elements Shape Stemness in Normal and Leukemic Hematopoiesis

status: Public on Jan 15 2026

city: Toronto

first: Mathieu

last: Lupien

state: Ontario

address: 101 College Street

institute: University Health Network

summary: Despite most acute myeloid leukemia (AML) patients achieving complete remission after induction chemotherapy, two thirds of patients will relapse with fatal disease within 5 years. AML is organized as a cellular hierarchy sustained by leukemia stem cells (LSC) at the apex, with LSC properties directly linked to tumor progression, therapy failure and disease relapse. Despite the central role of LSC in poor patient outcomes, little is known of the genetic determinants of their stemness properties. Although much AML research focuses on mutational processes and their impact on gene expression programs, the genetic determinants of cell state properties including stemness expand beyond mutations, relying on the genetic architecture captured in the chromatin of each cell. As LSCs share many functional and molecular properties with normal hematopoietic stem cells (HSC), we identified genetic determinants of primitive populations enriched for LSCs and HSCs in comparison with their downstream mature progeny by investigating their chromatin accessibility. Our work reveals how distinct transposable element families are used in primitive versus mature populations, functioning as docking sites for stem cell-associated regulators of genome topology or lineage-specific transcription factors in primitive and mature populations, respectively. We further show how transposable element families accessible in LSCs define docking sites for several oncogenic drivers in AML, including LYL1. Using chromatin accessibility profiles from a cohort of AML patients, we further show the clinical utility of our transposable element accessibility-based LSCTE121 scoring scheme to identify patients with high rates of relapse. Collectively, our work reveals how different accessible transposable element families serve as genetic determinants of stemness properties in normal and leukemic hematopoietic stem cells.

overall_design:
Assay for Transposase-Accessible Chromatin Sequencing (ATAC-Seq) performed on engrafting (LSC+) and non-egrafting (LSC-) leukemic cells and on bulk AML patients' peripheral blood samples
*** Raw data for these needs controlled access hence are already submitted to EGA (EGAS00001004893, EGAS00001004896 and EGAS00001007191). ***

Assay for Transposase-Accessible Chromatin Sequencing (ATAC-Seq) performed on OCI-AML22 CD34+/CD38- cells expressing CRISPR/dCas9 and scramble or LTR12C gRNA combos

first: Giacomo

last: Grillo

first: Héléna

last: Boutzen

first: Bettina

last: Nadorp

first: Ankita

last: Nand

first: John

last: Dick


title: Histone Lysine Methylation Dynamics Control EGFR DNA Copy-Number Amplification

status: Public on Jan 07 2026

city: Boston

first: Kashish

last: Chetal

state: MA

address: 55 Fruit St

department: Molecular biology

institute: MGH

summary: Acquired chromosomal DNA copy gains are a feature of many tumors; however, the mechanisms that underpin oncogene amplifi cation are poorly understood. Recent studies have begun to uncover the importance of epigenetic states and histone lysine methyltrans_x0002_ferases (KMT) and demethylases (KDM) in regulating transient site-specifi c DNA copy-number gains (TSSG). In this study, we reveal a critical interplay between a myriad of lysine methyltransferases and demethylases in modulating H3K4/9/27 methylation balance to control extrachromosomal amplifi ca_x0002_tion of the EGFR oncogene. This study further establishes that cellular signals (hypoxia and EGF) are able to directly promote EGFR amplifi cation through modulation of the enzymes controlling EGFR copy gains. Moreover, we demonstrate that chemical inhibitors targeting specifi c KMTs and KDMs are able to promote or block extrachromosomal EGFR amplifi cation, which identifi es potential therapeu

overall_design: Chromatin Immunoprecipitation DNA-Sequencing (ChIP-seq) for histone modifications H3K4me3 sites in RPE cells upon KDM5A siRNA depletion

first: Johnathan

last: Whetstine

first: Ruslan

last: Sadreyev


summary: Genome folding is not static, but emerges from dynamic processes that control transcription, replication, recombination, and repair. DNA loop extrusion by cohesin is central to genome organization, yet it remains unclear how cells can tune extrusion kinetics to achieve precise and functional chromosome folding patterns. Here we show that extrusion rate acts as a tunable biophysical parameter in cells, quantitatively dialed by the respective dosage of the cohesin cofactors NIPBL and PDS5. Modulation of extrusion rate can offset changes in cohesin lifetime to buffer steady-state chromosome structure and transcriptional states, even in the face of abnormal extrusion dynamics. These findings provide a long-sought mechanistic basis for the genetic interactions between cohesin cofactors and for the molecular origin of haploinsufficiency in cohesinopathies, such as Cornelia de Lange syndrome.

overall_design: Hi-C using in various mouse embryonic stem cell lines with auxin- or dTAG-inducible degrons inserted on endogenous NIPBL, RAD21, WAPL, PDS5A and PDS5B.


title: High-glucose environment impairs keratinocyte migration and proliferation through the ROS/Akt/ETV4 signaling pathway

status: Public on Jan 06 2026

city: Hefei

first: Hongfeng

last: Chang

state: Anhui

address: jixi road number 218

institute: The First Affiliated Hospital of Anhui Medical University

summary: The RNA-sequencing dataset comprises eight human immortalized keratinocyte samples cultured under high-glucose conditions. Cells were exposed to 35 mM glucose for 96 h and transfected with either ETV4-targeting small interfering RNA (siETV4) or negative-control small interfering RNA (siNC) for 48 h. Four independent biological replicates were included in each group. Normal-glucose and mannitol osmotic-control samples were used in separate cellular validation experiments but were not included in the RNA-sequencing dataset. Human immortalized keratinocytes within passages P21?P33 were maintained in customized RPMI-1640 medium containing 5.5 mM glucose (L210KJ, Yuanpei Biology, Shanghai, China), supplemented with 10% fetal bovine serum and 1% penicillin?streptomycin. For RNA sequencing, the glucose concentration was adjusted to 35 mM. Cells were exposed to high-glucose conditions for 96 h and transfected with siETV4 or siNC for 48 h.

first: Bing

last: Shen

first: Qiu

last: Zhang


title: Integrated stress response couples mitochondrial fitness with lineage reprogramming to drive cancer evolution.

status: Public on Jan 01 2026

city: Montréal

first: Antonis

last: Koromilas

state: QC

address: 3755 Chem. de la Côte-Sainte-Catherine

institute: Lady Davis Institute - McGill University

summary: Tumour progression towards dedifferentiated cell clusters plays a critical role in intratumour heterogeneity and therapy resistance. While tumour microenvironmental stress has been implicated, the underlying mechanisms remain poorly defined. Using mouse models of lung adenocarcinoma, we demonstrate that activation of the integrated stress response (ISR)—marked by phosphorylation of eIF2 (p-eIF2) and ATF4 induction—drives tumour heterogeneity. ISR activation facilitates the emergence of high-plasticity, undifferentiated and pre-epithelial-to-mesenchymal transition clusters characterized by elevated ATF4 and MYC activity. This process is MYC dependent and involves ISR-mediated repression of NKX2-1, a key determinant of alveolar identity, and induction of CHCHD10, a regulator of mitochondrial integrity and metabolic fitness. Disruption of the p-eIF2–ATF4 axis induces mitochondrial dysfunction, limits dedifferentiation and suppresses tumour growth. In human lung adenocarcinoma, ISR-driven dedifferentiation correlates with advanced disease and poor prognosis, identifying the ISR as a central driver of lineage reprogramming and metabolic fitness in tumour progression.

overall_design: To investigate the role of integrated stress response, specifically p-eIF2, in LUAD evolution, we conducted scRNA-seq on GFP+/CD45- lung tumor cells isolated by Fluorescence-Activated Cell Sorting (FACS).

first: Shiqi

last: Diao

first: Jia Yi

last: Zou


title: Spatial and single-nucleus transcriptomic profiling of CHB liver biopsies

status: Public on Dec 31 2025

city: Foster City

first: Ricardo

last: Ramirez

address: 333 Lakeside Drive

institute: Gilead Sciences

summary: A modified spatial transcrptomics workflow was used to profile liver tissues to compare viral and host-transcript profiles

overall_design:
The assay was tested on H&E stained FFPE samples from: 1) HBV infected uPA/SCID humanized mouse livers (one vehicle treated and one Tenofovir alafenamide treated), 2) cell pellets from PLC/PRF/5 cell line and primary human hepatocytes which where unifected or infected with genotypes C and B versions of HBV, and 4) commercially procured liver biopsy samples (2 healthy donors, 4 chronic HBV patients)

[UPDATE] The processed data files have been replaced and new samples have been added on June 9, 2026.

first: Sangeetha

last: Mahadevan

first: Hatef

last: Mehrabian

first: Subhra

last: Chaudhuri

first: Hsiu-Chun

last: Chuang

first: Kai-Hui

last: Sun

first: Anjali

last: Rao


title: Ex Vivo Hypothermic Perfusion Enables 48‐Hour Heart Preservation and Bench‐Top Functional Recovery via Normothermic Reperfusion in a Porcine Model

status: Public on Dec 24 2025

first: Ting

last: Peng

state: PA

address: CTRB 6200

department: Pathology and Laboratory Medicine

institute: Children's hospital of Philadelphia

summary: Background: Ex vivo oxygenated perfusion systems is a promising approach to extend cardiac allograft preservation beyond the typical 4–6h limit allowed by static-cold-storage (SCS).  Hypothermic oxygenated perfusion (HOPE) has been proven to safely preserve donor hearts, yet its underlying molecular mechanisms have not been extensively evaluated.   Objectives: The aim of the study is to characterize cardiomyocyte viability, transcriptomic and metabolomic responses, and functional recovery of porcine hearts preserved with HOPE for up to 48h, including evaluating their ability to regain sinus rhythm following bench-top normothermic reperfusion (NMP).  Methods: Seventeen Yorkshire pigs underwent donor cardiectomy. In the first arm, ten hearts were preserved for up to 48h using either SCS (n=5) or HOPE (n=5). Endomyocardial biopsies were collected at 0, 12, 24, and 48h for histology, RNA sequencing, flow cytometry, and metabolomics. In the second arm, six HOPE-preserved hearts (3h, 24h, 48h) and two SCS-preserved heart (3h and 24h) underwent 2h NMP to simulate transplantation and assess reanimation.  Results: HOPE preserved cardiomyocyte viability and structural integrity for 48h, in contrast to SCS in both arms of the study. RNA sequencing and untargeted metabolomics revealed conserved energy-substrate profiles in HOPE and progressive ischemic metabolite accumulation in SCS. All HOPE hearts regained stable sinus rhythm.  Conclusions: HOPE enables 48h ex vivo heart preservation while maintaining cardiomyocyte integrity, normal gross and microscopic architecture, and rapid functional recovery on bench-top reperfusion in a preclinical model. These findings establish a foundation for redefining clinical preservation times and widening geographic donor access.

overall_design: RNA-seq profiling of swine myocardial tissue biopsied (1) at T0h, T12h, T24h and T48h of either SCS or HOPE preservation, and (2) after  T3h, T24h and T48h of HOPE or T24h of SCS, followed by 2h of Normothermic Machine Perfusion.


title: Single-cell and spatial transcriptomics of A-P and D-V patterned human trunk embryoid model (hTEM)

status: Public on Dec 23 2025

city: Hong Kong

first: Tianming

last: Wu

state: Hong Kong

address: LKS Int Biomed Sci Bldg

department: School of Biomedical Sciences

institute: Chinese University of Hong Kong

summary: Human embryoid models enable mechanistic studies of development and disease. We generated trunk embryoids from human pluripotent stem cells that recapitulate posterior trunk formation at Carnegie stage (CS) 8-10, with patterned anterior-posterior (A-P) and dorsal-ventral (D-V) axes. These self-organizing structures comprise a ventral notochord, dorsal neural tube, floor plate and bilateral somites. Genetic and chemical perturbations of SHH signaling confirmed the notochord’s central role in D-V patterning. Moreover, VANGL1/2 loss-of-function mutations recapitulated mouse phenotypes, including axial truncation and somite segmentation failure. This model enables detailed study of key developmental events that underlie posterior trunk formation and provides a promising platform for human disease modeling.

overall_design: scRNA-seq of human trunk embryoid model v1 (hTEM.v1) at day 4/5/7, hTEM.v2 at day 5/7, hTEM.v3 at day 3/4/5/6/7 and day-6 hTEM.v3 derived from loss-of-function mutants including NOTO-LOF, SANT1 treatment (250 nM, days 4-6) and VANGL2-LOF. For spatial transcriptomics, Visium HD was applied onto hTEM.v2 (day7, transverse and longitudinal section) and hTEM.v3 (day 4 and day6.5, longitudinal section).

first: Hao

last: Yu

first: Brian

last: Wong

first: Ling

last: Xu

first: Joaquim

last: Vong

first: Stephen

last: Dalton


title: A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines.

status: Public on Dec 30 2025

first: Duane

middle: R.

last: Wesemann

address: 77 Avenue Louis Pasteur

department: Medicine, Division of Allergy and Clinical Immunology

institute: Brigham and Women's Hospital

summary: Inflammation initiated in response to a microbial encounter, or deliberately induced upon vaccination, is central for the activation of adaptive lymphocytes. The stimulation of pattern recognition receptors (PRRs) orchestrates the inflammatory programs that regulate adaptive immunity. Here, we took advantage of an mRNA-based vaccine generated against the ancestral spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to test whether tuning inflammation via PRR stimulation enhances the efficacy of mRNA vaccines. We combined mRNA-based vaccine with mannadjuvant, a formulation of fungal mannan and aluminum hydroxide that targets Dectin-2, a C-type lectin PRR. In mice and non-human primates, mannadjuvant increased the magnitude and durability of the response elicited by the mRNA-based vaccine, and it also led to the induction of neutralizing antibodies directed against variants of concern with a high escape capacity, overcoming antigenic imprinting. Mechanistically, we demonstrated that prolonged type I interferon production and potentiated interleukin-1 signaling are necessary and sufficient to exert the activities of mannadjuvant in mice and in human myeloid cells.  Overall, our data demonstrate that an anti-fungal PRR can be harnessed to create more potent and durable mRNA-based vaccines.

overall_design: We performed single-cell RNA sequencing (scRNA-seq) coupled with single-cell B cell receptor sequencing (scBCR-seq) in mice that received Comirnaty alone or Comirnaty formulated with mannadjuvant. As an additional group for direct comparison of B cell responses, mice were immunized with a monovalent Comirnaty vaccine developed against the spike protein of XBB.1.5 (hereafter referred to as XBB.1.5-Comirnaty). Briefly, C57BL/6 mice were immunized intramuscularly (i.m.) in the thigh muscle with Comirnaty alone or Comirnaty plus mannadjuvant. At day 56 after priming, the draining lymph nodes were collected and processed into single-cell suspensions by enzymatic digestion. A total of 1–2 × 10⁶ cells were stained with 0.5 µg of cell hashing antibodies (BioLegend Total-Seq™ C antibodies, Hashtags 1–12) following Fc receptor blocking with TruStain FcX™ PLUS (anti-mouse CD16/32; BioLegend, Cat. #156604), according to the manufacturer’s protocol. After incubation with hashing antibodies, cells were washed, stained with surface antibodies, and processed for fluorescence-activated cell sorting (FACS). Spike-positive germinal center (GC) B cells expressing B cell receptors (BCRs) specific for either WA1 or XBB.1.5 spike protein were sorted and subjected to scRNA-seq and scBCR-seq. Single-cell suspensions of FACS-sorted GC B cells from four biological samples were processed using the Chromium GEM-X Single Cell 5′ Reagent Kit v3 (Cat. #1000699, 10x Genomics) and the Single Cell 5′ Gel Bead Kit v3 (Cat. #1000700, 10x Genomics). Cells (27,000–35,000 per channel) were loaded onto a Chromium X Series instrument (10x Genomics) to generate single-cell gel beads-in-emulsion (GEMs), following the manufacturer’s instructions. The recovery rate was approximately 45–55%. Captured cells were lysed within individual GEMs, and released RNA was barcoded during reverse transcription. 5′ gene expression (GEX) libraries, single-cell V(D)J libraries (Cat. #1000255, 10x Genomics), and cell surface protein libraries were prepared according to the manufacturer’s protocols. Library quality was assessed using an Agilent 2200 TapeStation, and final libraries were quantified by qPCR using the KAPA Library Quantification Kit for Illumina platforms. Libraries were diluted to 2 nM and pooled into two separate batches. A total of 650 pM of pooled libraries was mixed with 5% PhiX control library prior to sequencing. Sequencing was performed in two independent runs on an Illumina NextSeq 2000 platform using the P4 XLEAP-SBS Reagent Kit (200 cycles), with paired-end reads configured as follows: 28 cycles for read 1, 10 cycles for the i7 index, 10 cycles for the i5 index, and 90 cycles for read 2. Sequencing achieved a median depth of approximately 32,000 reads per cell for gene expression, 55,000 reads per cell for BCR libraries, and 5,000 reads per cell for hashtag (ADT) libraries.

first: Kautilya

last: Jena

first: Pengxiang

last: Qu

first: Lauren

last: Baracco

first: Shahab

last: Saghaei

first: Keerti

last: Keerti

first: Zahra

last: Allahyari

first: Daniel

last: Boehmer

first: Moriah

last: Mitchell

first: Carly

last: Dillen

first: Hai-Yun

last: Li

first: Enqi

last: Liu

first: Valentina

last: Poli

first: Océane

last: Dufies

first: David

last: Hoytema van Konijnenburg

first: Roberto

last: Spreafico

first: Caihong

last: Bi

first: Rebecca

last: Hall

first: Michael

last: Kruppa

first: Zuchao

last: Ma

first: Amy

last: Gravitte

first: Douglas

last: Lowman

first: Harry

last: Ensley

first: Pierre

last: Marty

first: Laurent

last: Boyer

first: Rémy

last: Collomp

middle: L

last: Wiliams

first: Victor

first: Pui

last: Lee

first: Peter

last: Nigrovic

first: Jeffrey

last: Karp

last: Elledge

middle: R

first: Yi

first: Matthew

last: Frieman

first: Ivan

last: Zanoni


title: Peptidyl-tRNA hydrolase 2 is an essential negative regulator of peripartum cardiomyopathy with maternal heart failure (human and mouse RNA-seq)

status: Public on Dec 22 2025

city: Torrance

first: Michelle

last: Matter

address: 1124 West Carson Street

department: Genomics

institute: The lundquist Institute

summary: The peptidyl-tRNA hydrolase 2 (PTRH2, Bit-1; BIT1) gene plays a pro-survival role during development with loss of function gene mutations causing congenital infantile multisystem disease (IMNEPD). In wild-type female mice hearts, ptrh2 protein levels significantly increase during pregnancy and decrease postpartum, demonstrating a protective role in response to pregnancy-initiated cardiac stresses. Peripartum cardiomyopathy (PPCM) is due to dysregulated protective signaling in the pregnant heart. The genetic and molecular mechanisms underlying PPCM remain poorly defined with no specific therapies. Here, we engineered a cardiac-specific Ptrh2 knockout (Ptrh2-CKO) mouse and show these maternal mice develop left ventricular systolic dysfunction, exhibit high rates of postpartum heart failure, and model key features of human PPCM. Infusion of a caspase 3-specific inhibitor attenuated the PPCM phenotype. Collectively, our findings demonstrate Ptrh2 is a negative regulator of pregnancy-induced cardiac stresses by activating pro-survival signals and blocking apoptotic signals, suggesting Ptrh2 may be a therapeutic target for the treatment of PPCM

overall_design: RNA-seq of LV tissue from donor and PPCM patients. The hypothesis tested in the present study was that pregnancy induced stress alters gene expression that may lead to maternal heart failure. Results identify up-and down-regulated genes that are altered in PPCM/DCM (humans and mice).

first: Vanessa

last: Montoya-Uribe

first: Pooja

last: Choubey


title: Combined epigenetic therapy with FACT and BET inhibitors remodels chromatin and disrupts oncogenic transcription in Diffuse Midline Glioma [Xenium]

city: Kensington

first: Holly

last: Holliday

address: Lowy Cancer Research Centre

country: Australia

institute: Children's Cancer Institute

summary: Aberrant epigenetic regulation is a hallmark of Diffuse Midline Glioma (DMG), an incurable pediatric brain tumor. The H3K27M driver histone mutation leads to transcriptional dysregulation, indicating that targeting the epigenome and transcription may be key therapeutic strategies against this highly aggressive cancer. One such target is the Facilitates Chromatin Transcription (FACT) histone chaperone. We found FACT to be enriched at developmental gene promoters, coinciding with regions of open chromatin and binding motifs of core DMG regulatory transcription factors. Furthermore, FACT interacted and co-localized with the Bromodomain and Extra-Terminal Domain (BET) protein BRD4 at promoters and enhancers, suggesting functional cooperation between FACT and BRD4 in DMG. In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition revealed potent and synergistic cytotoxicity across a range of DMG cultures. These results were recapitulated in vivo, significantly extending survival in three independent orthotopic PDX models of DMG. Mechanistically, we show that CBL0137 treatment decreased chromatin accessibility, synergizing with BET inhibition to cause broad transcriptional collapse, silencing several key oncogenes including MYC, PDGFRA, MDM4 and SOX2, as well as causing alterations to the splicing landscape. Notably, this combination also elicited immune-related effects, including activation of the interferon response and antigen presentation mechanisms in DMG cells and induction of an activated state in macrophages and T cells, as demonstrated in an immunocompetent setting with spatial transcriptomics. Altogether, our data highlights the therapeutic promise of simultaneously targeting FACT and BET proteins in DMG, offering a dual tumor-intrinsic and immune-mediated strategy for combating this devastating pediatric brain tumor.

overall_design: 5-7 weeks old female C57BL6 mice were intracranially injected into the brainstem with IUE 24B7 cells that harbor H3.3K27M mutation generated in (doi: 10.1093/neuonc/noz197 and 10.1093/noajnl/vdac079). The timing of treatment initiation was 18 days post intracranial surgery. The drug treatments were as follows: CBL0137 - dissolved in 5% dextrose, CBL0137 was administered intravenously at a dosage of 40 mg/kg/day. The treatment was given once every four days for a total of three weeks. JQ1 - dissolved in DMSO and subsequently in a solution containing 0.9% saline with 5% PEG400 and 5% TWEEN-80, JQ1 was administered at a dosage of 50 mg/kg/day intraperitoneally. The treatment was given five days a week over three weeks. Brain samples were collected on the final day of treatment and fixed in a 10% formalin neutral buffered solution (Sigma-Aldrich). The fixed samples were then embedded in paraffin wax, and 5 µm sections were cut and mounted onto Xenium slides, with two brains per slide. Xenium Prime In Situ (10x Genomics) was performed according to the manufacturer’s instructions using the 5000 pre-designed gene panel and cell segmentation staining. Briefly, priming oligos were hybridized to the target RNA, followed by site-specific cleavage using RNase treatment to release the RNA strand from the hybridized oligo. The 5000-gene panel was then added to the sections to hybridize with the RNA, followed by ligation to generate circular DNA probes, which were subsequently amplified via rolling circle amplification. After a series of ethanol washes, the tissue was blocked and stained with the cell segmentation stain and DAPI. Slides were then loaded into the Xenium Analyzer for imaging and decoding. Spatial Transcriptomics Services for this study were provided by the Garvan Genomics Platform at the Garvan Institute of Medical Research.


title: Gemcitabine and nab-paclitaxel with or without the VDR agonist paricalcitol for metastatic pancreatic cancer: A randomized, multi-arm, phase I trial

status: Public on Dec 21 2025

first: Jonathan

middle: Andrew

last: Nowak

address: 75 Francis St.

department: Pathology

summary: Vitamin D receptor (VDR) agonists promote quiescence of cancer-associated fibroblasts and improve efficacy of chemotherapy in preclinical models of pancreatic cancer. We conducted a phase I trial (NCT03520790) with primary endpoint of safety when the VDR agonist paricalcitol is given with first-line gemcitabine and albumin-bound paclitaxel (GA) in patients with metastatic pancreatic cancer. Secondary endpoints included pharmacodynamic analyses. Thirty-six patients were randomized to GA plus placebo, GA plus intravenous paricalcitol or GA plus oral paricalcitol with pre-treatment and on-treatment tumor biopsies. Paricalcitol was safely administered with GA, although 5 (42%) patients receiving oral paricalcitol had grade 2-4 hypercalcemia and required dose reduction. Nuclear VDR protein expression was heterogeneous across patients, and VDR was expressed in tumor, immune, and stromal cells. Compared to pre-treatment specimens, on-treatment biopsies had decreased proportion of αSMA+ fibroblasts, altered fibroblast VDR activation signature, and greater density and spatial colocalization of CD8+ T cells with tumor cells in the GA plus paricalcitol arms. VDR expression was predictive of tumor response in the GA plus paricalcitol arms. Paricalcitol can be safely administered with chemotherapy to patients with metastatic pancreatic cancer, and on-treatment biopsies indicated favorable modulation of the tumor microenvironment by paricalcitol as predicted by preclinical models.

overall_design: A total of 50 tissue slides (31 pre-treatment, 19 on-treatment) were profiled using the GeoMx Digital Spatial Profiler (DSP) and multiple regions of interest (ROI) were selected within areas containing tumor after hybridization with the Human Whole Transcriptome Atlas (WTA) probe mix.  Next, the ROIs were further segmented into areas of illumination (AOIs) using a customized contouring approach, in which cytokeratin is used as a reference to define three non-overlapping areas for ultraviolet light-directed barcode collection: center (tumor epithelial region), ring 1 (stromal region within 1-25 um of the tumor epithelial region), and ring 2 (stromal region within 26-50 um of the tumor epithelial region). The barcodes were then deposited into 96-well plates, subjected to library preparation, and sequencing using S1 flow cells on an Illumina NovaSeq instrument. Samples then underwent demultiplexing. Lastly, raw read counts were analyzed to generate AOI-level expression data. The data was then quality-controlled and third-quartile normalized, resulting in a dataset including counts from 18,412 probes from 676 areas of illumination.

first: Andressa

last: Dias Costa

first: Alexander

last: Jordan

first: Brian

last: Wolpin


title: DeCAF redefines fibroblast states uncovering multidimensional tumor-stroma relationships driving clinical tumor progression and immunotherapy response

status: Public on Dec 18 2025

city: Chapel Hill

first: Jen Jen

last: Yeh

state: North Carolina

address: 450 West drive

institute: The University of North Carolina at Chapel Hill