title: Selective nucleophagy removes cytotoxic trapped PARP1

status: Public on Mar 23 2026

city: Oxford

first: Gwendoline

last: Hoslett

address: MRC Weatherall Institute of Molecular Medicine (Oxford University & John Radcliffe Hospital)

department: Oncology

summary: Poly (ADP-ribose) polymerase inhibitors (PARPi) induce cytotoxicity in homologous recombination deficient cancers by causing PARP1 to become trapped on chromatin, resulting in irreparable replication-associated DNA damage. Cancer cells commonly develop resistance to PARPi, with a recently proposed mechanism being the clearance of trapped PARP1 from chromatin, yet details surrounding this process remain unclear. PARPi treatment causes increased autophagy flux, whilst autophagy inhibition can hypersensitise cells to PARPi. With selective autophagy of nuclear substrates (nucleophagy) shown, we wanted to explore if this occurs during DNA damage repair by clearance of trapped PARP1. We used various biochemical, cell biological and live imaging-based assays, demonstrating that trapped PARP1 is processed by selective nucleophagy. We identified that nucleophagy of trapped PARP1 is orchestrated by selective autophagy receptor TEX264 and its partner protein p97/VCP. TEX264 directly interacts with trapped PARP1, then bridges PARP1 to autophagosomal resident protein LC3 for processing via autophagy. Impeding this process, either chemically or genetically, heightened PARP1 trapping, leading to replication-associated DNA damage and cell lethality, re-sensitising PARPi-resistant cells to various PARPi. In conclusion, we show that selective nucleophagy acts in a cytoprotective manner to directly target PARPi-induced trapped PARP1 for degradation.

overall_design: To investigate the role of TEX264 in PARP inhibitor response, we developed TEX264 knockout cell lines in HeLa and CAL51. We then performed gene exression profiling by RNA-seq after 24 hours of talazoparib treatment with 2 repeats for CAL51 and 3 repeas for HeLa. We performed comparative gene expression profiling to compare wild type cells with and without treament and TEX264-KO cells to wild type with treatment.


title: N6-methyladenosine modulate second cell fate decision by enhancing mRNA stability of pivotal transcription factors during primitive endoderm development [EPSC_RNA-seq]

city: Beijing

first: Li

last: Tang

state: Beijing

address: No.5 Yiheyuan Road Haidian District

country: China

institute: Peking University

type: Expression profiling by high throughput sequencing

summary: Transcription factors (TFs) have key roles in cell fate determination, and are rapidly upregulated to fulfill developmental functions. During second cell fate decisions in pre-implantation embryonic development, upregulated key TFs, including GATA6 and NANOG, drive the differentiation and functional establishment of primitive endoderm (PrE) and epiblast (EPI) cells. However, how the embryo achieves this swift TF upregulation and the precise molecular mechanisms underlying specific TF initiation remain unclear. In this study, we showed how N6-methyladenosine (m6A) affected embryo and embryoid differentiation. Using two types of extended pluripotent mouse embryonic stem cells with in vivo embryonic and extraembryonic potency-extended pluripotent stem cells (EPSCs) and totipotent blastomere-like cells (TBLCs) alongside mouse embryos, we observed that the m6A writers METTL3 and VIRMA were essential for PrE development. Mechanistically, globally increased mRNA stability occurred during embryo development - mediated by m6A modification. Specifically, m6A enhanced key regulator stability during PrE differentiation, such as Gata6, by interacting with the m6A reader IGF2BP3, thereby promoting protein production and ultimately impacting on cell fate decisions. Our results suggest that post-transcriptional mRNA regulation is a pioneering mechanism governing second cell fate decisions, and highlights the molecular mechanisms underlying mouse embryogenesis.

overall_design: This study characterized the transcriptomic states of EPSCs and investigated the RNA stability across different states.

first: Weide

last: Xiao

first: Mingli

last: Ma

first: Kuisheng

last: Liu


title: N6-methyladenosine modulate second cell fate decision by enhancing mRNA stability of pivotal transcription factors during primitive endoderm development  [TBLC_RNAseq]

overall_design: This study characterized the transcriptomic states of TBLCs and investigated the RNA stability across different states.


title: N6-methyladenosine modulate second cell fate decision by enhancing mRNA stability of pivotal transcription factors during primitive endoderm development [mESC_RNA-seq]

overall_design: This study characterized the transcriptomic states of mESCs and investigated the RNA stability across different states.


title: Transcriptional characterization of Mycobacterium tuberculosis-specific memory T cell subset response

city: Newark

first: Padmini

last: Salgame

state: NJ

address: 185 South Orange Ave

department: Medicine

country: USA

institute: Rutgers New Jersey Medical School

summary: We provide transcriptional profiles of CD4+ memory T cell subsets in response to M. tuberculosis antigen stimulation of cells obtained from donors with confirmed latent TB infection (LTBI) to interrogate the memory recall response.  We observe that different memory T cell subsets exhibit unique responses to Mtb stimulation.

overall_design: Transcriptome profiles via RNAseq of sort-purified CD4+ stem cell memory, central memory, transitional memory, and effector memory T cells [4 cell types], under conditions of co-stimulation plus Mtb antigen stimulation or co-stimulation only [2 treatment conditions], obtained from five LTBI donors [5 subjects].

first: Samantha

last: Leong


title: N6-methyladenosine modulate second cell fate decision by enhancing mRNA stability of pivotal transcription factors during primitive endoderm development  [GLORI]

overall_design:
The study was designed to investigate the impact of Virma on the m6A methylation profile in TBLC. To achieve this, we employed a gene knockdown approach using siRNA to specifically deplete Virma within TBLC . Following the knockdown, we utilized the GLORI to comprehensively assess the changes in the m6A methylation landscape.
This experiment was designed to validate the m⁶A demethylation efficiency of the dCas13b-FTO-sgRNA targeting system.


title: Retinoic acid drives cell fate specification, maturation and retinal regionality in human retinal organoids [Visium]

status: Public on Mar 22 2026

city: Sydney

first: Carissa

last: Chen

state: NSW

address: 214 Hawkesbury Rd, Westmead

country: Australia

institute: Children's Medical Research Institute

summary: Retinoic acid (RA) is a key morphogen in human retinal development, activating transcriptional programs that drive retinal progenitor differentiation and photoreceptor development, ensuring proper spatial organisation within the neural retina, essential for vision. Despite its well-established role in retinal patterning, the concentration-dependent effects of RA on human retinal cell fate specification and the regional definition of the primate macula and peripheral retina remain poorly understood. Here, we show that temporal and dosage-dependant modulation of RA during human retinal organoid differentiation induces distinct changes in retinal cell abundance, maturation, and organisation. Single-cell transcriptomics and protein analysis revealed that RA dosage influenced the relative abundance and maturation of photoreceptors and retinal interneurons. Spatial transcriptomics analyses demonstrated that low RA levels biased retinal organoids toward a macular-like regional identity, whereas high RA levels promoted peripheral-like development. Collectively, our findings emphasise the critical role of RA signalling in retinal maturation and regional specification. This study elucidates mechanisms involved in human retinal development and we anticipate that controlled RA modulation in retinal organoids provides a strategy to refine disease modelling of inherited retinal disorders and enhance the specific generation of photoreceptors suitable for transplantation and regenerative therapies.

overall_design: 6-15 retinal organoids differentiated from the H7 A81.BRN3b.mCherry and iPSC 149br.CRX.Cherry reporter lines (with 2 replicates each) were collected at 10 weeks. Slides were stained with DAPI to be analysed. Single organoids per slide were manually segmented and the corresponding gene expression data was concatenated into a SpatialExperiment object.

first: Benjamin

middle: Y

last: Lim

first: Anna

last: Fredericks

first: Elham

last: Nilli

first: Santiago

middle: M

last: Mora

first: Megan

last: Weatherstone

first: To Ha

last: Loi

first: Peter

last: Newman

first: Nader

last: Arymanesh

first: Hala

last: Zreiqat

first: Patrick

last: Tam

first: Pengyi

last: Yang

first: Anai

last: Gonzalez-Cordero


title: Retinoic acid drives cell fate specification, maturation and retinal regionality in human retinal organoids [Stereo-seq]

overall_design: 4-21 retinal organoids differentiated from the H7 A81.BRN3b.mCherry reporter line were collected at 16 and 26 weeks. Organoids were sectioned onto BGI Stereo-seq transcriptomic slides, fixed and tissue was permeabilised. Slides were then stained with ssDNA to be analysed. Using the bioinformatic pipeline provided by BGI, gene expression was aggregated in square arrays of 30um x 30um (bin60) when analysing 16 week organoid samples and 50um x 50um (bin100) when analysing 26 week organoid samples

first: Hal


title: Retinoic acid drives cell fate specification, maturation and retinal regionality in human retinal organoids [scRNA-seq]

overall_design: Five to six organoids differentiated from the H7 A81.BRN3b.mCherry reporter line were collected after treatment with 10uM, 1uM retinoic acid, no retinoic acid or 1uM BMS-493 and analysed with scRNA-seq


title: The B cell receptor-mTOR signaling axis restricts the accumulation of lung tissue-resident memory B cells following influenza infection

status: Public on Mar 20 2026

city: St. Louis

first: Brian

last: Laidlaw

state: MO

address: 425 S Euclid Ave

institute: Washington University in St. Louis

summary: Lung tissue-resident memory B (BRM) cells are important in establishing protective immunity against respiratory pathogens. However, the pathways regulating the accumulation of lung BRM cells are poorly understood. Here we show that the transcription factors NFATC1 (nuclear factor of activated T cells 1) and EGR2 (early growth response 2) repress lung BRM cell accumulation following influenza infection, whereas IKZF1 (IKAROS family zinc finger 1) enhances it. IKZF1 restrains B cell receptor (BCR) and mTOR (mechanistic target of rapamycin) signaling and is highly expressed in lung BRM cells during their development. Lung BRM cells display reduced expression of genes associated with BCR and mTOR signaling pathways. Overexpression of a degradation-resistant form of SYK downstream of the BCR restricted lung BRM cell accumulation. Conversely, inhibition of mTOR using rapamycin reduced NFATC1 and EGR2 expression and promoted lung BRM cell accumulation. These findings establish how the BCR–mTOR signaling axis regulates mucosal B cell responses following influenza infection.

overall_design: We performed gene expression profiling using data obtained from RNA-seq analysis of germinal center-derived memory B cell subsets defined based on their expression of CXCR3 and whether they were labeled by in vivo injection of CD45.2 on day 30 post influenza PR8 infection.

first: Laidlaw

last: Brian


title: N6-methyladenosine modulate second cell fate decision by enhancing mRNA stability of pivotal transcription factors during primitive endoderm development

first: Li

last: Tang

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

overall_design: Refer to individual Series


title: Ubiquitylation by the GID/CTLH complex regulates the metabolic and innate immune response of macrophages to infection by Mycobacterium tuberculosis

status: Public on Mar 18 2026

city: Ithaca

first: Nelson

middle: Victor

last: Simwela

state: NY

address: 930 Campus Rd

department: Microbiology and Immunology

institute: Cornell University

summary: The GID/CTLH E3 ligase complex is implicated in several biological processes, yet its full substrate repertoire remains poorly defined. We recently identified the complex as a broad modulator of macrophage responses to Mycobacterium tuberculosis (Mtb) infection.  Here, we use label-free proteomics and diGly capture analysis of Mtb-infected macrophages to define the GID/CTLH-dependent ubiquitylome. We identify thousands of dynamically altered ubiquitylation sites, with strong enrichment among proteins involved in cellular metabolism and innate immune signaling. Concurrent proteome analysis revealed extensive rewiring in GID/CTLH-deficient macrophages, with >90% of enriched pathways among increased proteins consisting of metabolic targets. Notably, inhibitory phosphatases (PTEN, INPP5D) also emerged as candidate substrates. Functional studies revealed proteasome-dependent stabilization of PTEN and INPP5D in GID/CTLH-deficient macrophages with each phosphatase individually exerting an influence on Mtb intracellular survival. Together, our study defines a GID/CTLH-dependent ubiquitylome in macrophages and identifies the complex as a central regulator of metabolism and antimicrobial immunity.

overall_design: Anlysis of the transcriptional profile of Mtb infected murine macrophages in either wild type state or INPP5D knockout conditions treated or untreated with the INPP5D inhibitor 3AC.

middle: V

first: Luana

last: Johnston

first: Chris

last: Sassetti

first: David

middle: G

last: Russell


title: Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis [kras_inhibitor_scRNA-seq]

city: New York

first: Yu-Jui

last: Ho

address: 1275 York Avenue

institute: Memorial Sloan Kettering Cancer Center

summary: The transition from benign to malignant growth is a pivotal yet poorly understood step in cancer progression that marks the shift from a pathologically inert condition to a clinically lethal disease. Here, we integrate lineage tracing, single-cell and spatial transcriptomics to visualize the molecular, cellular and tissue-level events that promote or restrain malignancy during the tumor initiation in mouse models of pancreatic ductal adenocarcinoma (PDAC). We identify a discrete progenitor-like population of KRAS-mutant cells that co-activates oncogenic and tumor-suppressive programs—including p53, CDKN2A, and SMAD4—engaging senescence-like responses and remodeling their microenvironment, ultimately assembling a niche that mirrors invasive PDAC. Even brief KRAS inhibition in the epithelial compartment depletes progenitor-like cells and dismantles their niche, substantially delaying cancer initiation. Conversely, p53 suppression enables progenitor cell expansion, epithelial–mesenchymal reprogramming, and immune-privileged niche formation. These findings position the progenitor-like state as the convergence point of cancer-driving mutations, plasticity, and tissue remodeling—revealing a critical window for intercepting malignancy at its origin.

overall_design: To assess the consequences of acute oncogenic Kras inhibition on the spectrum of pancreatic premalignant states in the context of pancreatic injury, we subjected 5-week-old KPLOH (Ptf1a-Cre; LSL-KrasG12D; Rosa26-CAGS-LSL-rtTA3-IRES-mKate2; p53flox/wt; TRE-GFP-shRen.713) mice to eight-hourly intraperitoneal injections of 80 μg kg-1 of caerulein (Bachem) for two consecutive days (16 injections total). In addition, we treated mice with MRTX1133 (30mg/kg) or vehicle concurrently with caerulein treatment, euthanizing mice within 4 h of the last MRTX1133 or vehicle dose (fifth dose, 2 days after the first dose).

first: José

last: Reyes

first: Scott

middle: W

last: Lowe

first: Dana

last: Pe'er


title: Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis [Multiome-seq]

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: To assess the spectrum and dynamics of premalignant states and tissue remodeling events in the in the context of oncogenic KRAS activation in the premalignant epithelium, we subjected 5–6-week-old male mice with eight-hourly intraperitoneal injections of 80 μg kg-1 of caerulein (Bachem) for two consecutive days (16 injections total). Caerulein dose was adjusted to body weight at the beginning of each day of treatment. We harvested the pancreata at 2 days after the first caerulein injection, collecting single cells for single cell RNA and ATAC multiome analysis.


title: Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis [injury_shp53_scRNA-seq]

overall_design: To assess the spectrum and dynamics of premalignant states and tissue remodeling events in the in the context of oncogenic KRAS activation in the premalignant epithelium, we subjected 5–6-week-old male mice with eight-hourly intraperitoneal injections of 80 μg kg-1 of caerulein (Bachem) for two consecutive days (16 injections total). Caerulein dose was adjusted to body weight at the beginning of each day of treatment. We harvested the pancreata at 3 weeks post-caerulein treatment, collecting single cells for scRNA-seq.


title: Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis [Xenium]

overall_design: Spatial transcriptomic using Xenium (10X) of mouse premalignant pancreas. All samples come from mice with oncogenic KrasG12D activation in pancreatic epithelial cells during embryonic development (Ptf1a-Cre; LSL-KrasG12D). Each sample metadata specifies the experimental condition:   1. K2_ctrl: p53 proficient pancreatic epithelium, subjected to injury-induced pancreatitis on day -1 and day 0, sample collected on day 2.  2. K2d1_ctrl: p53 proficient pancreatic epithelium, subjected to injury-induced pancreatitis on day -1 and day 0, sample collected on day 2.  3. K3_ctrl: p53 proficient pancreatic epithelium, subjected to injury-induced pancreatitis on day -1 and day 0, sample collected 3 weeks after.  4. K2_shp53: p53 knockdown in pancreatic epithelium, subjected to injury-induced pancreatitis on day -1 and day 0, sample collected on day 2.  5. K2d1_shp53: p53 knockdown in pancreatic epithelium, subjected to injury-induced pancreatitis on day -1 and day 0, sample collected on day 2.  6. K3_shp53: p53 knockdown in pancreatic epithelium, subjected to injury-induced pancreatitis on day -1 and day 0, sample collected 3 weeks after.  7. K2_MRTX1133: p53 proficient pancreatic epithelium, subjected to injury-induced pancreatitis on day -1 and day 0, followed by 5 doses of MRTX1133 (two doses per day). Sample collected after the fifth dose.  8. K2_vehicle: p53 proficient pancreatic epithelium, subjected to injury-induced pancreatitis on day -1 and day 0, followed by 5 doses of vehicle (two doses per day). Sample collected after the fifth dose.  9. K4: p53 proficient pancreatic epithelium without injury. Collected 4.5 months after birth.


title: Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis


title: Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis [FLEX]


title: Hierarchical microtopology and phase-specific delivery functionally restore ultra-long nerve continuity across species

status: Public on Mar 17 2026

city: Suzhou

first: Xiaoyu

last: Lin

address: No. 100, Chongwen Road, Suzhou Industrial Park

institute: Suzhou Institute of Systems Medicine

summary: Repairing ultra-long peripheral nerve defects remains a major clinical challenge, primarily due to the requirement for regenerative platforms to be capable of integrating spatial guidance with temporally resolved biochemical cues. To address this, we developed a clinically translatable, fully synthetic nerve conduit that aligns with native regenerative principles through hierarchical microtopological engineering and phase-specific molecular delivery. This design creates a pro regenerative microenvironment by synchronizing structural cues with repair cascades. The neuroanatomically inspired core mimics the endoneurium and perineurium, providing extensive cell scale contact guidance for axonal alignment and fasciculation. A dual-layered sheath ensures mechanical integrity, metabolic permeability, and selective exclusion of fibrotic tissue. Tailored to align with distinct phases of nerve repair, the conduit enables sequential release of spermidine and ascorbic acid. Spermidine resolves early inflammation, priming the niche for ascorbic acid-mediated debris clearance, axonal elongation, and remyelination. In both rat (2 cm) and beagle (5 cm) models of critical-sized sciatic nerve defects, the conduit supports structural and functional regeneration comparable to autografts, while yielding superior outcomes in motor coordination and suppression of autotomy. This strategy offers a scalable and mechanistically informed solution for repairing ultra long nerve injuries with high translational promise.

overall_design:
In this study, we developed a clinically translatable, fully synthetic nerve conduit that aligns with native regenerative principles through hierarchical microtopological engineering and phase-specific molecular delivery. This design creates a pro regenerative microenvironment by synchronizing structural cues with repair cascades. The neuroanatomically inspired core mimics the endoneurium and perineurium, providing extensive cell scale contact guidance for axonal alignment and fasciculation. A dual-layered sheath ensures mechanical integrity, metabolic permeability, and selective exclusion of fibrotic tissue. Tailored to align with distinct phases of nerve repair, the conduit enables sequential release of spermidine and ascorbic acid. Spermidine resolves early inflammation, priming the niche for ascorbic acid-mediated debris clearance, axonal elongation, and remyelination.
Experimental model and sample source:
The transcriptomic data were obtained from regenerated rat sciatic nerve tissues. A 2-cm long-gap sciatic nerve defect model was established in rats, and the nerve gap was bridged using three different types of nerve conduits.
Fourteen days after implantation, regenerated tissues within the conduits were collected. Total RNA was extracted from these regenerated nerve tissues for transcriptomic sequencing, with the aim of investigating the influence of conduit structural guidance and bioactive molecule delivery on early-stage nerve regeneration.
Three experimental groups were included in this dataset:
Hollow group:
A hollow nerve conduit without any internal guidance structures.
AFMC group:
A biomimetic nerve conduit containing internal guidance structures. The lumen of the conduit is filled with aligned fibers (AF) and multiple longitudinal microchannels (MC), which provide physical guidance cues for axonal regeneration. Because the conduit integrates both aligned fibers and microchannels, it is referred to as the AFMC conduit.
AFMC-AA-SP group:
Based on the AFMC conduit, bioactive molecules were incorporated with spatially differentiated loading. Spermidine (SP) was adsorbed onto the surface of the aligned fibers, while L-ascorbic acid (AA) was loaded inside the fibers. This design enables sequential release of the two bioactive molecules. In the early stage after implantation, SP is rapidly released from the fiber surface to modulate the inflammatory microenvironment. During later stages of regeneration, AA is gradually released from the fiber interior, contributing to neurotrophic support and promoting myelin remodeling.
This dataset therefore allows the evaluation of:
The effect of multiscale structural guidance on nerve regeneration (AFMC vs. Hollow)
The additional effect of bioactive molecule delivery on tissue regeneration (AFMC-AA-SP vs. AFMC)

first: Shuxin

last: Dai


title: Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis [KPLOH scRNA-seq]

overall_design: To study the consequences of p53 loss of heterozygosity during pancreatic cancer initiation, we conducted single cell RNA sequencing on dissociated epithelial cells derived from the KPLOH mouse model. In this system, Kras-mutant epithelial cells that retain wild-type p53 are mKate2/GFP double-positive, whereas cells undergoing spontaneous p53 LOH become mKate2 single-positive due to co-deletion of a physically linked GFP reporter. We isolated collected mKate2+/GFP+ and mKate2+/GFP- cells from mice that did not have a macroscopic tumor mass (pretumor stage), and from mice that had macroscopic PDAC (tumor stage).


title: Insights into the gene regulation of Listeria monocytogenes incubated on corn salad

status: Public on Mar 16 2026

city: Hamburg

first: Tim

last: Hoffmann

state: Hamburg

address: Ohnhorststraße 18

country: Germany

institute: Universität Hamburg

summary: Listeria monocytogenes is an important food-borne pathogen which is frequently linked to ready-to-eat vegetables. In this work it was investigated by RNA-seq how the colonization of corn salad leaves and the commonly used packaging material polystyrene impacts on the transcriptome of L. monocytogenes NCTC 10887 at 4 °C and 22 °C. The strongest transcriptional differences occurred on corn salad at 4 °C versus polystyrene at 4 °C, yielding 2,629 differentially expressed genes (91.6% of protein-coding genes), indicating a habitat driven shift under cold-chain conditions. Corn salad promoted regulation of virulence related genes. The prfA gene was upregulated on corn salad compared to polystyrene at both temperatures (log2FC 2.43 at 22 °C and 4.16 at 4 °C), accompanied by increased hly (2.70), inlA (4.46), and inlB (2.10) expression at 4 °C. Stress/proteostasis gene expression was elevated on corn salad, including higher transcripts of clpP (3.34–3.51), clpE (5.58–6.89), and clpB (2.08–3.74), consistent with a stressed yet persistence-prone state on leaf surfaces. This indicates that L. monocytogenes persisting on leafy greens can remain transcriptionally primed for host interaction at 4 °C, implying that refrigeration alone may not mitigate risk on ready-to-eat produce, underlining the importance of pre-harvest hygiene.

overall_design: Prokaryotes RNA-seq Analysis of Listeria monocytogenes NCTC 10887 incubated on corn salad (Valerianella locusta) and polystyrene at 4 °C and 22 °C for 24 h.

first: Hoffmann

last: Tim


title: HBV cccDNA Generated Using Single-Stranded M13 Phage DNA for Authentic Minichromosome Functionality

city: Shanghai

first: Yumeng

last: Li

address: 131 Dong'an Road

institute: Fudan University

summary: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists as minichromosomes in the nuclei of hepatocytes and serves as the transcriptional template for viral RNAs. The cccDNA pool, characterized by a low copy number, poses challenges for cccDNA research. To accurately mimic the full-length sequences and structure of HBV cccDNA, we developed a novel method using an M13 phage-based system and deoxyribozyme to produce full-length single-strand DNA (ssDNA) corresponding to both the positive and negative strands of cccDNA. This method involves the cyclization of the ssDNA followed by the addition of T4 DNA ligase, thereby producing the cccDNA. The in vitro cyclized cccDNA, formed by M13 phage-derived single-stranded DNA (McccDNA), allows the formation of minichromosomes in transiently transfected hepatic cells, recapitulates key stages of the HBV life cycle, and effectively responds to multiple antiviral drugs. Additionally, McccDNA was observed to more accurately transcribe major viral RNAs than recombinant cccDNAs containing exogenous sequences, and was also able to organize nucleosomes in a sequence-specific manner, resembling those events during natural viral infection. In conclusion, McccDNA generated from single-stranded M13 phage DNA recapitulates key natural properties of HBV cccDNA, and serves as an authentic and promising model to study cccDNA minichromosomes functionality.

overall_design: Nucleosome postioning of HepG2-NTCP cells transfected with McccDNA was profiled by MNase-seq.

first: Ting

last: Hua


title: Disrupting SOX2 Self-Association and Condensates to Overcome Chemotherapeutic Drug Resistance in Lung Squamous Cell Carcinoma [RNA-Seq, 2]

status: Public on Mar 14 2026

city: GuangZhou

first: Wen

last: Yulin

state: Guangdong

address: No.190 Kaiyuan Avenue

institute: Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS)

summary: Chemotherapy remains one of the most important treatments for lung squamous cell carcinoma (LSCC), yet overcoming chemotherapeutic drug resistance poses a significant challenge. The high frequency of SOX2 copy number amplification observed in LSCC patients underscores its potential role as a regulator in this context. Our investigation reveals a strong correlation between SOX2 amplification and expression levels in LSCC patients. Notably, overexpression of SOX2 confers resistance to chemotherapeutic drugs in LSCC cell lines. We elucidate that SOX2 undergoes phase separation, forming condensates that sequester chemotherapeutic agents used in LSCC treatment, thereby exacerbating chemotherapeutic drug resistance in LSCC cells. To address this, we design a small peptide containing 16 amino acids conjugated with 8 arginine, specifically targeting α-helix within HMG domain to disrupt SOX2 self-association. Our data demonstrate that this peptide effectively prevents SOX2 droplet formation, consequently reversing chemotherapy tolerance in LSCC without compromising SOX2 transcriptional activity. Collectively, our findings unveil a novel mechanism of chemotherapy resistance in LSCC mediated by SOX2 phase separation and propose a promising peptide-based therapeutic strategy to combat chemoresistance in LSCC.

overall_design: Gene expression profiling of NCI-H520 cells in ultrapure water control group and after 12 hours of 10 μM Hx1R8 treatment group.

first: Juehan

last: Wang

first: Yulin

last: Wen

first: Sainan

last: Huang

first: Yanjiang

last: Liu

first: Hongjie

last: Yao


title: Disrupting SOX2 Self-Association and Condensates to Overcome Chemotherapeutic Drug Resistance in Lung Squamous Cell Carcinoma [Cut & Run, 2]

overall_design: CUT&Run of SOX2 in NCI-H520 cells in ultrapure water control group and after 12 hours of 10 μM Hx1R8 treatment group.


title: Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells

city: Salt

first: Javier

middle: Abel

last: Menendez

state: Girona

address: Dr Castany s/n. Parc hospitalari Marti i Julia

country: Spain

institute: Girona Biomedical Research Institute

summary: Conventional chemotherapeutic agents and radiation induce accelerated senescence in cancer cells, a phenomenon known as therapy- induced senescence (TIS). Here, we investigated whether TIS can also be induced by targeted inhibition of de novo lipogenesis, which we term fatty acid synthesis therapy-induced senescence (FASTIS). SKBR3 breast cancer cells were treated for 7 days with clinically relevant inhibitors of the key lipogenic enzymes acetyl-CoA carboxylase (ND-646) and fatty acid synthase (TVB-3166) as well as with the well-established, mechanistically distinct TIS inducers bleomycin (an antibiotic that promotes oxidative stress), alisertib (an Aurora A kinase inhibitor that promotes mitotic stress), doxorubicin (a topoisomerase II inhibitor and DNA intercalator that induces DNA damage stress), and palbociclib (a CDK4/6 inhibitor that induces replication stress). To understand the unique versus shared molecular changes of the FASTIS phenotype induced by fatty acid synthesis inhibitors compared to other TIS inducers, we performed mRNA-Seq experiments to provide a comprehensive, high-resolution view of the underlying coding transcriptomes. To account for potential artifacts due to cell subpopulations entering a quiescent state to survive nutrient deprivation after 7 days, parallel mRNA sequencing was also performed in untreated (proliferative) cells at days 0 and 7.

overall_design: RNA-seq profiling of SKBr3 cells treated with de novo lipogenesis inhibitors (ND-646 and TVB-3166) or well-established senescence inducers (bleomycin, alisertib, doxorubicin, palboclib) at days 0 and 7.

first: Àngela

last: Llop-Hernández

first: Sara

last: Verdura

first: Travis

last: Van der Steen

first: José Antonio

last: Encinar

first: Begoña

last: Martin-Castillo

first: Elisabet

last: Cuyàs

first: Ruth

last: Lupu

first: Javier A.


title: HIV Transgenic Mouse Monocytes Display Increased In Vivo Migration Across the Blood Brain Barrier Associated with Increased Expression of Genes Associated with Mononuclear Leukocyte Migration

status: Public on Mar 13 2026

city: Bronx

first: Harris

last: Goldstein

address: 1300 Morris Park Avenue

department: Pediatrics

institute: Albert Einstein College of Medicine

summary: Soon after HIV acquisition, circulating HIV-infected monocytes cross the blood-brain barrier (BBB) and infect resident brain microglia and other susceptible cells, establishing a potential viral reservoir. Despite supressive antiretroviral therapy, these HIV-infected cells mediate a neuroinflammatory process causing HIV-associated neurocognitive deficites (HAND) in at least 20% of people with HIV. Continued migration of HIV-infected monocytes into the brain may further exacerbate neuroinflammation and replenish viral reservoirs. To ascertain how HIV infection facilitates monocyte passage across the BBB in vivo, we developed a novel mouse model to quantify circulating monocytes supporting HIV production that migrated into the brain. We demontrate that significantly more monocytes from HIV-transgenic mice, capable of supporting HIV production, crossed the BBB compared to control transgenic mouse monocytes. This difference was particularly pronounced after recipient mice were treated with lipopolysaccharide (LPS). To explore the underlying mechanism, we compared the transcriptomes of HIV transgenic mouse monocytes and control mouse monocytes and identified multiple differentially expressed genes linked to mononuclear leukocyte trafficking, including several associated with monocyte chemotaxis. We also evaluated the effect of substance use in combination with HIV infection on monocyte migration across the BBB into the brain by treating HIV transgenic mice with either morphine or methamphetamine. Short-term exposure to either drug did not significantly alter the migration of HIV-transgenic monocytes across the BBB.

overall_design: RNA-seq profiling of WT (CCC mice) and HIV (JRCCC mice) CD11b monocytes in the presence and absence of LPS treatment (3 mg/kg; 24 hour treatment)

first: Sydentricker

last: Agnes

first: Lee

last: Danica

first: Voss

last: Adilyn

first: Zheng

last: Jian

first: Hur

last: Hong

first: Kandpal

last: Manoj

first: Goldstein

last: Harris


title: Disrupting SOX2 Self-Association and Condensates to Overcome Chemotherapeutic Drug Resistance in Lung Squamous Cell Carcinoma [RNA-Seq]

first: Wen

last: Yulin

overall_design: Gene expression profiling of NCI-H520 cells in PBS control group and after 48 hours of 2 μM cisplatin treatment group.

first: Juehan

last: Wang

first: Yulin

last: Wen

first: Sainan

last: Huang

first: Yanjiang

last: Liu

first: Hongjie

last: Yao


title: Disrupting SOX2 Self-Association and Condensates to Overcome Chemotherapeutic Drug Resistance in Lung Squamous Cell Carcinoma [CUT&Run]


title: Disrupting SOX2 Self-Association and Condensates to Overcome Chemotherapeutic Drug Resistance in Lung Squamous Cell Carcinoma


title: GFI1 regulates NK cell maturation and function [scMultiome-seq].

city: Brisbane

first: M. Zeeshan

last: Chaudhry

state: Queensland

address: 37 Kent Street

institute: The University of Queensland

summary: Natural killer cells defend against malignancies and viral infections through a tightly controlled program of differentiation and maturation. However, the transcriptional mechanisms guiding this process remains incompletely defined. Using paired single cell multiomic profiling, we show that the transcriptional repressor GFI1 epigenetically regulates key molecular programs, including EOMES and T-BET balance, to promote NK cell proliferation and transition from immature to terminally differentiated NK stages. GFI1 was shown to repress FOXO1 chromatin accessibility in mature NK cells, which normally represses NK cell proliferation and maturation. Co-deletion of both GFI1 and FOXO1 largely rescued NK cell differentiation identifying a critical GFI1-FOXO1 axis essential for protection against tumour metastasis. These findings position GFI1 as an important transcriptional node integrating NK cell differentiation, activation, and effector programming.

overall_design: NK cells isolated from spleen of naïve NcriCreT/+, NcriCreT/+Gfi1fl/fl, NcriCreT/+Foxo1fl/fl and NcriCreT/+Gfi1fl/flFoxo1fl/fl mice were sequenced using BD Rhapsody WTA+ATAC sequencing kit.

first: Zeeshan

first: Gabrielle

last: Belz


title: Drosophila 3rd instar larvae, full body at single-nucleus transcriptome resolution

city: Boston

first: Yanhui

last: Hu

state: MA

address: 77 Avenue Louis Pasteur

department: Genetics

institute: Harvard Medical School

summary: Drosophila 3rd instar larvae contain numerous developing and differentiated tissue-types and organs. We generated this single-nucleus transcriptome to help compare the results of a companion tissue secretome proteomic dataset.

overall_design: Whole Drosophila 3rd instar larvae were pooled, dissasociated into nuclei, and sequenced separately, then bioinformatically pooled to make an atlas.

first: Justin

last: Bosch

first: Norbert

last: Perrimon


title: GFI1-FOXO1 axis regulate NK cell maturation and function [RNA-seq]

summary: Natural killer cells protect against malignant and virally-infected cells through a tightly regulated differentiation, maturation, and homeostatic program. The signals guiding differentiation of NK cells has not yet been fully elucidated. GFI1 is a transcriptional repressor broadly expressed in bone marrow progenitors and adaptive immune cells and acts to shape differentiation but has not been defined in NK cells. We show that GFI1 is differentially expressed across NK cell subsets but is not required for the development of immature (Imm) NK cell. Instead, GFI1 regulates the checkpoints that control the transition from Imm to mature NK stages (M1 and M2). Using multiomics approaches, we show that GFI1 regulates FOXO1 and EOMES signalling in mature NK cells and is critical for NK cell division and maturation. Furthermore, we show that the GFI1-FOXO1 axis is essential for protection against tumor metastasis through NK cell activation and effector functions, highlighting the important role of GFI1 in innate immune regulation.

overall_design: For NK cell RNA-seq, NK cell subsets including CD11a-KLRG1- Immature NK, CD11a+KLRG1- M1 NK and CD11a+KLRG1+ M2 NK cells were isoalted from spleen of Ncr-cre, Ncr-cre.Gfi1fl/fl, Ncr-cre.Foxo1fl/fl and Ncr-cre.Gfi1fl/fl.Foxo1fl/fl. Total RNA was isolated from the NK cells and RNA-seq was performed.

first: Qiutong


title: Sex and tissue resolved co-expression networks reveal a female placental–brain axis protective against prenatal PCB exposure

status: Public on Mar 12 2026

city: Davis

first: Janine

last: LaSalle

state: California

address: 1275 Med Science Dr

institute: University of California, Davis

summary: Background: Neurodevelopmental disorders have a strong male bias that is poorly understood, Placenta is a rich source of molecular information about environmental interactions with genetics (including biological sex), that affect the developing brain. We investigated placentalbrain transcriptional responses in an established mouse model of human-relevant prenatal exposure to polychlorinated biphenyls (PCBs). Results: To understand sex, tissue, and dosage effects in embryonic (E18) brain and placenta RNAseq datasets, we used weighted gene correlation network analysis (WGCNA) to create correlated gene networks that could be compared across sex or tissue. WGCNA revealed that expression within most correlated gene networks were significantly and strongly associated with PCB exposures, but frequently in opposite directions between male-female and placenta-brain comparisons. In both WGCNA and differentially expressed gene analyses, male brain showed more PCB-induced transcriptional changes than male placenta, but the reverse pattern was seen in females. Furthermore, non-monotonic dose responses to PCBs were observed in most gene networks, but were most prominent in male brain. The transcriptomic effects of low dose PCB exposure were significantly reversed by dietary folic acid supplementation across both sexes, but these effects were strongest in female placenta. PCB-dysregulated and folic acid reversed gene networks were commonly enriched in functions in metabolic pathways involved in energy usage and translation, with female-specific protective effects enriched in PPAR, thermogenesis, glycerolipids, and O-glycan biosynthesis, as opposed to toxin responses in male brain. Conclusions: The female protective effect in prenatal PCB exposures appears to be mediated by dose-dependent sex differences in transcriptional modulation of metabolism in placenta.

overall_design: The experiment was designed to test the hypothesis that PCB-induced transcriptional changes in the placental-brain axis will be affected by both dosage and sex. The PCB MARBLES mixture, consisting of PCB 28 (48.2%), PCB 11 (24.3%), PCB 118 (4.9%), PCB 101 (4.5%), PCB 52 (4.5%), PCB 153 (3.1%), PCB 180 (2.8%), PCB 149 (2.1%), PCB 138 (1.7%), PCB 84 (1.5%), PCB 135 (1.3%) and PCB 95 (1.2%), was formulated to mimic the 12 most abundant congeners identified from the serum of pregnant women in the ASD-enriched MARBLES cohort, as previously described.32 C57BL/6J female mice (Jackson Laboratory) aged 6 to 8 weeks were orally exposed to 4 different doses (0, 0.1, 1.0, or 6.0 mg/kg/d) of the PCB mixture in peanut oil (Spectrum Organic) and peanut butter (Trader Joe’s Organic Creamy). The PCB mixture was stored as concentrated stock in peanut oil, then diluted in peanut butter to make dosing mixes for the four dose groups (0, 0.1, 1, and 6 mg/kg/d). The dosing mixes were premade for the entire experiment and stored in the refrigerator and remixed daily. For alterations to folic acid in the chow, mice were fed ad libitum, with the AIN-93G purified diet, containing with or without 6 ppm folic acid supplementation (ENVIGO 190757, 94045, respectively). Females were dosed daily for at least 2 weeks before breeding commenced. Daily dosing then continued through breeding and gestation, up to embryonic day 18 (E18). On E18, pregnant females were euthanized in a CO2 euthanasia chamber. Immediately after euthanasia, embryos were removed, and tissues dissected and flash frozen.

first: Kelly

last: Chau

first: Kari

last: Neier

first: Anthony

middle: E

last: Valenzuela

first: Rebecca

middle: J

last: Schmidt

first: Blythe

last: Durbin-Johnson

first: Pamela

last: Lein

first: Ian

last: Korf


title: Peroxisomes orchestrate metabolic flexibility and longevity via an interorganelle cascade

status: Public on Mar 11 2026

first: William

middle: B.

last: Mair

address: 677 Huntington Ave, Boston,

institute: Harvard School of Public Health

summary: Aging impairs coordinated organelle dynamics essential for lipid metabolism, causing a decline in intracellular metabolic flexibility. However, the drivers of organelle collapse and their temporal order remain unclear. Here, we identify peroxisomal function as a critical regulator of metabolic flexibility during youth and low-energy states. Using Caenorhabditis elegans, we show that fasting robustly induces peroxisomal function in youth, while this response is blunted during aging. Loss of peroxisomal import via PRX-5 declines over age, causing pathological lipid droplet expansion, dysfunctional mitochondrial bioenergetics, and metabolic inflexibility. While targeted PRX-5 degradation recapitulates metabolic aging, its overexpression preserves lipid dynamics and mitochondrial integrity. Notably, dietary restriction maintains peroxisomal pathways and organelle coordination into late life, and peroxisomal function causally underpins dietary restriction-mediated longevity. Our findings highlight peroxisomes as central, upstream regulators of a dynamic inter-organelle cascade driving metabolic plasticity and highlight peroxisomal maintenance as a key determinant of metabolic flexibility during aging.

overall_design: Expression profiling by high throughput RNA sequencing. Wild-type N2 C. elegans were subjected to RNA expression profiling at ages young adult (YA, young) and day 8 (D8, adult) under fed and 6 hour fasted conditions to specifically identify genes either induced/repressed with fasting in young but not aged animals.

first: Arpit

last: Sharma

first: Aditi

last: Prabhakar

first: Miriam

last: Valera-Alberni

first: Jamie

middle: D

last: Kraft

first: Abigail

last: Ellis

first: Ryan

last: Sheldon

first: Meeta

last: Mistry

first: Pallas

first: Yanshan

last: Liang

first: Sheng

last: Hui

middle: B


title: Brain-Engrafted Monocyte-derived Macrophages from Blood and Skull-Bone Marrow Exhibit Distinct Properties [bulkRNA_braintissue]

first: Jonathan

last: Kipnis

address: 4515 McKinley Ave

summary: Microglia arise from yolk sac (YS) progenitors and are thought to persist throughout life with minimal input from adult hematopoiesis. However, whether brain-engrafted monocyte-derived macrophages (MDM) exist at homeostasis and during turnover, and how they function relative to yolk sac-derived microglia (YSM) remain unsettled. Here, we combine lineage tracing, pharmacological microglia depletion, and multi-omics profiling to define the ontogeny, identity, and function of MDM in the mouse brain. Despite sharing the parenchymal milieu, MDM display unique transcriptional and epigenetic landscapes distinct from YSM. Fate-mapping reveals that newly engrafted MDM transiently express CD206, echoing a developmental stage of embryonic microglial precursors. The engraftment and polarization of MDM are modulated by the CSF1R ligand IL 34 and the chemokine receptor CCR2. Furthermore, parabiosis and skull‑flap transplantation reveal that both blood and skull marrow supply the niche via distinct routes, yielding origin‑biased MDM states. Functionally, engraftment of MDM exacerbates cuprizone-mediated demyelination. Together, our study reveals the cellular dynamics of brain parenchymal macrophages at homeostasis and during turnover. We define the core molecular features and heterogeneous origins of MDM and imply their context-dependent roles in CNS pathology.

overall_design: For RNA isolation from brain tissue, the forebrain of NT-, PLX-1x-, IR-BMT- and PLX-3x-treated mice was dissected and snap-frozen on dry ice. Total RNA was extracted using the RNeasy Lipid Tissue Mini Kit (Qiagen) following the manufacturer’s protocol with minor modifications.

first: Siling

last: Du

first: Feiya

last: Ou

first: Antoine

last: Drieu

first: Eric

last: Xu

first: Yumeng

last: Cheng

first: Steffen

last: Storck

first: Tornike

last: Mamuladze

first: Jay

last: Cao

first: Nora

last: Abduljawad

first: Bishan

last: Bhattarai

first: Justin

last: Rustenhoven

first: Niall

last: Mortimer

first: Simone

last: Brioschii

first: Khai

last: Nguyen

first: Patrick

middle: F

last: Rodrigues

first: Igor

last: Smirnov

first: Daniel

last: Gibson

first: J

last: White

first: Wandy

last: Betty

first: David

last: DeNardo

first: Qingyun

last: Li

first: Michael

last: Meers

first: Claudia

middle: Z

last: Han

last: Sun

first: Florent

last: Ginhoux

first: Marina

last: Cella

first: Marco

last: Colonna


title: Brain-Engrafted Monocyte-derived Macrophages from Blood and Skull-Bone Marrow Exhibit Distinct Properties [bulkRNA_isolatedBrainParenchymalMacrophages]

first: Jonathan

last: Kipnis

overall_design: For RNA isolation of sorted cells, brain parenchymal macrophages were purified from PLX5622-treated or IR-BMT-treated mouse brains using FACSAria II (BD Biosciences) as live, negative for Ly6C, Ly6G, CD206, CD44; positive for CD45 and CD11b. From the brain parenchymal macrophage gate, tdTomato+ and tdTomato- macrophages were sorted into different tubes containing cold RLT Plus buffer (from RNeasy Micro Plus Kit, RQiagen) supplied with 2-Mercaptoethanol (Sigma).

first: Siling

last: Du

first: Feiya

last: Ou

first: Antoine

last: Drieu

first: Eric

last: Xu

first: Yumeng

last: Cheng

first: Steffen

last: Storck

first: Tornike

last: Mamuladze

first: Jay

last: Cao

first: Nora

last: Abduljawad

first: Bishan

last: Bhattarai

last: Rustenhoven


title: Whole transcriptome sequencing of UPEC-infected testis and epididymis (5d) following depletion of CX3CR1+ macrophages

city: Giessen

first: Marek

last: Bartkuhn

state: Hessen

address: Aulweg 132

department: Biomedical Informatics and Systems Medicine

institute: Justus-Liebig-University Giessen

summary: A finely tuned immune regulation within the epididymis and testis—balancing tolerance towards sperm with effective defense against infections—is essential for maintaining male fertility. This balance is especially critical in the epididymis, where sperm mature and where it is often disrupted during ascending urogenital infections. While testicular inflammation is typically reversible, the epididymis undergoes irreversible tissue remodeling, particularly in distal regions, whereas proximal regions remain mostly unaffected despite bacterial presence.  We previously identified that each epididymal region has a unique immunological landscape, distinct from that of the testis. Notably, CX3CR1⁺ macrophages are the dominant immune cell type and appear central to maintaining homeostasis and orchestrating immune responses in a region-specific manner.  To assess their functional role, we used a transgenic mouse model to deplete CX3CR1⁺ macrophages under steady-state and infected conditions. Whole-transcriptome analysis following E. coli infection revealed downregulation of genes linked to innate immunity and cytokine regulation, indicating that CX3CR1⁺ macrophages restrain excessive inflammation—particularly in proximal regions.  Combined with histological and cellular phenotyping, our data highlight a key role for CX3CR1⁺ macrophages in preserving epithelial integrity and modulating immune responses during infection.

overall_design: Intraepithelial CX3CR1+ macrophages  were selectively depleted using Cx3cr1CreERT2/+Rosa26iDTR/tdTomato transgenic mice). After Dtx-mediated depletion of CX3CR1+ macrophages, an acute bacterial epididymitis was elicited by intravasal injection of uropathogenic Escherichia coli. Testes, proximal and distal epididymal regions were collected for whole transcriptome analysis 5 days after infection. Mice treated solely with Tamoxifen (for induction of DTR expression under the CX3CR1+ promotor control) without subsequent Dtx treatment served as comparator.

first: Christiane

last: Pleuger

first: Tara

last: Procida-Kowalski

first: Linda

last: Kreyling

first: Andreas

last: Meinhardt


title: A Role for Rapid Transcription Dynamics in Cytarabine Resistance in Acute Myeloid Leukemia

status: Public on Mar 09 2026

first: Russell

last: Scharf

state: New York

address: 1945 Eastchester Rd

summary: Chemotherapy resistance remains a critical challenge in the treatment of patients with cancer including acute myeloid leukemia (AML). While genetic alterations contribute to chemotherapy resistance, rapid-adaptive non-genetic mechanisms, particularly transcription dynamics, remain poorly understood. Given the role of cell-intrinsic transcriptional variability in cell fate decisions, understanding and targeting chemotherapy-induced changes in transcription dynamics could offer new strategies to prevent chemotherapy resistance. In this study, we demonstrate that short-term treatment with the widely used chemotherapeutic cytarabine (AraC) leads to the rapid emergence of RNA-induced AML cells with increased AraC resistance in both cell lines as well as primary patient samples. Mechanistically, through global transcriptomic analyses and targeted high-resolution analysis of transcription dynamics using single-molecule RNA FISH, we found rapid induction of transcriptional dynamics and upregulation of key transcription factors (TFs) - which we term “AraC rapid response TFs (ARR-TFs)” and which include PU.1 and GATA1 – following chemotherapy treatment. At a functional level, short-term pre- and co-treatment with RNA transcription inhibitors effectively suppressed chemotherapy-induced RNA induction and prevented resistance acquisition, in both in vitro and in vivo models. Furthermore, we found that CRISPR-mediated suppression of PU.1 and GATA1 induction significantly attenuated AraC resistance. In summary, our findings reveal a previously unrecognized role of rapid and early adaptive transcriptional dynamics in AML chemotherapy resistance, highlighting master TFs as key regulators of drug resistance. These insights offer a novel, pharmacologically targetable and accessible approach to alleviate chemotherapy resistance, and encourage further testing with the ultimate goal to improve AML treatment outcomes.

overall_design: HL60 cells were treated with 250nM AraC for 1 day. Cells were then stained for Pyronin Y and Hoechst and Pyronin Y low and high fraction within G0/G1 gated cells were sorted using flow cytometry for RNA seq analysis

first: Goichi

last: Tatsumi

first: Rajni

last: Kumari

first: Yutaro

last: Suzuki

first: Shuting

last: Li

first: Samuel

last: Taylor

first: Sriram

last: Sundaravel

first: Amit

last: Verma

first: Justin

last: Wheat

first: Ulrich

last: Steidl


title: A Role for Rapid Transcription Dynamics in Cytarabine Resistance in Acute Myeloid Leukemia [ATAC-seq]

overall_design: HL60 cells were treated with 250nM AraC for 1 day (Day 1 sample) or 3 days followed by cuture in non-drug media for another 9 days (Day 14 sample). Controls were treated with the AraC solvent DMSO.

last: Suzuku


title: A Role for Rapid Transcription Dynamics in Cytarabine Resistance in Acute Myeloid Leukemia [RNA-seq]

overall_design: HL60 cells were treated with 250nM AraC for 1 day. Controls were treated with the AraC solvent DMSO. Cells were stained for Pyronin Y and Hoechst and G0/G1 cells were sorted using flow cytometry for RNA seq analysis

first: Taylor

last: Samuel


title: Intra-tumoral microbiota and host genotype cooperatively shape neutrophil antitumor activity in colorectal cancer

city: Bellinzona

first: Giandomenica

last: Iezzi

address: via chiesa 5

department: Department of Surgery and Gut Division

country: Switzerland

institute: Institute for Translational Research USI-EOC (IRT)

summary: The role of tumor-associated neutrophils (TANs) infiltrating colorectal cancers is still debated. Here we unravel that TAN recruitment and functions are modulated by intra-tumoralmicrobiota and only defined bacterial species are able to unleash TANs’ antitumor potential. Fusobacterium nucleatum (Fn) promotes production of neutrophil-recruiting chemokines bytumor cells and enhances neutrophil migration more efficiently than Bacteroides fragilis (Bf). Importantly, Fn, but not Bf, triggers neutrophils to release cytotoxic proteins showingtumoricidal activity in vitro and in xenograft models. Mechanistically, these antitumor effectsare elicited upon Fn binding to Siglec-14 expressed by neutrophils but are impaired uponSiglec-14 blockade or loss-of-function polymorphism. Supporting these findings, in humanCRCs, elevated Fn loads, high TANs densities, and expression of wild-type, but notpolymorphic, Siglec-14 allele, correlate with improved patient survival. Our findings identify microbiota composition and host genetic background as criticaldeterminants of TAN functional profiles and offer insights into neutrophil-targeted therapeutic strategies in CRC.

overall_design: We performed single cell RNA-seq (WTA BD Rhapsody™) of non-stimulated, Fn-stimulated, and Bf-stimulated neutrophils from Siglec-14 WT or -Null donors (total of 6 samples).

first: Elisa

last: Sorrenti

first: Valeria

last: Governa


title: Reconstitution of spermatogenesis and continuous generation of functional haploid germ cells in mouse testicular organoids

status: Public on Mar 08 2026

city: Guangzhou

first: Qi

address: No.1023,South Shatai Road, Baiyun District

department: Developmental biology

institute: Southern Medical University

type: Methylation profiling by high throughput sequencing

summary: Testicular organoids that support spermatogenesis and generate functional haploid germ cells are still lacking. Here, we developed a formation-differentiation culture approach to generate optimized testicular organoids (O-Torgs) derived from neonatal mouse primary testicular cells. These O-Torgs could essentially recapitulate the seminiferous tubule morphogenesis, Sertoli cell maturation and testosterone secretion. Importantly, O-Torgs not only support spermatogenesis but also sustain proliferative undifferentiated spermatogonia and continuous generation of functional haploid cells for up to three months, with offspring derived from these haploid cells displaying normal growth and reproductive capability to F2 generation. Mechanistically, we found that the formation stage enhanced the reconstruction of tubule-like structures and subsequent spermatogenesis by providing a more conducive extracellular matrix niche. Finally, O-Torgs were proved to be effective in modeling male infertility and drug screening, with BTT-3033 acting as a potential drug in protecting busulfan-mediated germ cell loss. Overall, our work establishes a strategy to obtain functional testicular organoids, offering promising avenues for male infertility modeling and drug discovery.

overall_design: Refer to individual Series

first: Xiaoyang

last: Zhao

first: Fang

last: Luo

first: Kai

last: Miao

first: Cong

last: Wan


title: spatial transcriptomics of mouse brain before and after activation

city: Beijing

first: xiaoqun

last: wang

address: 15 Datun Road, Chaoyang District

department: Institute of Biophysics

institute: Chinese Academy of Sciences

summary: to unravel the intricate neural mechanisms that underpin the brain's complex functions through neural circuit, we selected two important neural circuits,  using optogenetic technology to activate specific circuits and applying spatial transcriptomics technology to explore the molecular mechanisms under the activation process

overall_design: we collect control and activated mice brain samples respectively for spatial transcriptomics to explore the molecular changes after neural circuit activation.


title: Bulk RNA-seq Analysis of Testis Tissues from Normal and Model Mice

summary: We provide bulk RNA-seq data generated from testicular tissue samples of mice treated with Vehicle, BU+PBS, and BU+BTT-3033.

overall_design: Bulk RNA-seq of testis tissues from normal and model mice treated with Vehicle, BU+PBS, and BU+BTT-3033.


title: Two LEAFY homologues regulate floral patterning and development without affecting flowering time in kiwifruit

city: Auckland

first: Yongyan

last: Peng

state: Auckland

address: 120 Mt Albert Road

department: Kiwifruit New Cultivars

country: New Zealand

institute: Plant and Food Research

summary: Actinidia chinensis (kiwifruit) are economically important fruit-bearing woody perennial vines, but with a long juvenile phase which slows plant breeding efforts. LEAFY (LFY) encodes a plant specific transcription factor central to the reproductive pathway in many plants, and its overexpression can accelerate flowering including in some trees. We identified two kiwifruit LFY (AcLFY) genes, expressed in actively-growing apical buds. Overexpression of AcLFY1 or AcLFY2 promoted flowering in Arabidopsis, but did not accelerate flowering in kiwifruit. Instead, branching at the lower nodes and changes in leaf morphology were observed. CRISPR-Cas9 targeted mutagenesis of AcLFY1 and/or AcLFY2 in a fast-flowering hermaphrodite kiwifruit background generated single and double mutants. The mutants flowered at the same time as control lines. Single mutants developed normal flowers, but double knockout mutations had severe effects on floral patterning and floral organ development. Petals and stamens were strongly affected, impacting on self-pollination, fruit size and shape. RNA-seq showed the two AcLFY genes were differentially regulated by the expression of a floral repressor CENTRORADIALIS gene AcCEN4. These results suggest that the AcLFY genes control plant architecture and contribute together to floral organ development and floral patterning which has implications for successful pollination and fruit set in kiwifruit.

overall_design: RNA-seq profiling of kiwifruit shoot apices over-exprssing the floral repressor AcCEN4 (pHEX2:AcCEN4-6xHA) comapred to the empty vector kiwifruit control. RNA-seq profilling of fast flowering kiwifruit shoot apices (floral repressor AcCEN and/or AcCEN4 CRISPR-Cas9 gene edited) compared to the wild type kiwifruit shoot apices.

first: Charlotte

last: Voogd

first: Cecilia

last: Deng

first: Mikaela

last: Douglas

first: Bo

last: Yang

first: Tianchi

last: Wang

first: Andrew

last: Allan

first: Erika

last: Varkonyi-Gasic

first: Joanna

last: Putterill


title: RNA-seq analysis of carbon framework-mediated metabolic reprogramming in senescent cells: effects of C3N nanosheets and photoactivation

status: Public on Mar 04 2026

first: xuelian

address: Ruijin er road No.197

institute: Ruijin hospital

summary: This RNA-seq dataset investigates the senolytic effects of carbon nitride quantum dots (C3N QDs) combined with irradiation on senescent human umbilical vein endothelial cells (HUVECs). The study compares three experimental conditions: senescence alone (S), senescence treated with C3N QDs (S+C), and senescence treated with C3N QDs followed by irradiation (S+C+I). Transcriptomic profiling revealed that the combined treatment (S+C+I) significantly reprogrammed gene expression patterns associated with aging and inflammation. Specifically, the S+C+I group showed a notable upregulation of genes such as MAPT, FOXO4, and PTEN, while markedly downregulating key senescence-associated secretory phenotype (SASP) factors including IL6, CXCL8, SERPINE1, and TERT compared to the S group. These data provide comprehensive insights into the molecular mechanisms by which C3N QDs-mediated photoactivation alleviates cellular senescence and suppresses pro-inflammatory pathways.

overall_design: The study comprises three experimental conditions: 1. S group: Senescent cells (control) 2. S+C group: Senescent cells treated with C3N QDs 3. S+C+I group: Senescent cells treated with C3N QDs followed by irradiation

first: Xuelian

first: Hanyu

last: Ma

first: Zhen

last: Li


title: tRNA-seq profiling of RKO colorectal cancer cells under arginine restriction

city: Pittsburgh

first: Parham

last: Habibzadeh

state: PA

address: 200 Lothrop Street

department: Department of Medicine

institute: University of Pittsburgh Medical Center

type: Non-coding RNA profiling by high throughput sequencing

summary: Here, we investigate how arginine limitation leads to changes in the cell tRNA pool using a YAMAT-seq-adapted protocol, the library was contructed based on illumina truseq small RNAseq library protocol for the adaptors and barcodes

overall_design: 4 biological replicates of arginine-replete (400 uM, "Feed") and 4 of arginine-restricted (12.5 uM) RKO cells treated for 24 hours. Paired-end 150 bp sequencing was subsequently performed on Illumina platform.

first: Qiushuang

last: Wu

first: Sohail

last: Tavazoie

first: Dennis

last: Hsu


title: Female iPSC X-chromosome inactivation (XCI) erosion and its transcriptomic effects during CRISPR gene editing and neural differentiation

city: Evanston

first: Christina

last: Thapa

state: Illinois

address: 1001 University Place

department: Center for Psychiatric Genetics (CPG)

institute: Endeavor Health

summary: Human induced pluripotent stem cells (hiPSC) and iPSC-differentiated neural cells, in combination with CRISPR editing, are commonly used for studying neurodevelopmental and other brain disorders. Female iPSCs undergo random X-chromosome inactivation (XCI) via epigenetic silencing by noncoding X inactive specific transcript (XIST). It is known that female iPSCs may lose XIST expression, leading to XCI erosion that affects both X-linked and autosomal gene expression. However, the effects of CRSIPR editing and neural differentiation on XCI erosion in iPSC-derived neurons and how this may confound a real-world transcriptomic analysis of differentially expressed genes (DEGs) are poorly understood. Here, leveraging bulk RNA-seq of hundreds of CRISPR-edited female iPSC lines from four donor lines for 66 genes and single-cell RNA-seq of iPSC-derived neurons of a subset of 42 edited genes, we investigated the effects of XCI erosion during CRISPR editing and in iPSC-derived neurons. We found that XCI erosion was variable in CRISPR-edited female iPSCs and largely preserved in iPSC-derived neurons. Like in iPSCs, XIST in neurons predominately influenced the expression of X-linked genes; however, its effect on autosomal genes was more pronounced in single neurons. Mechanistically, XIST epigenetically causes allelic imbalance of both X-linked and autosomal genes, with the former showing stronger allele-specific expression (ASE) bias. Notably, XIST-induced ASE bias exhibited a conserved positional pattern at loci affecting neurodevelopmental genes across different female lines and cell types. Finally, we demonstrated a confounding effect of XCI erosion on DEG analyses in iPSC-derived neurons. These results have significant implications in hiPSC modeling of neurodevelopmental and other brain disorders.

overall_design:
As part of the SSPsyGene Consortium, our Assay and Data Generation Center (ADGC) for the Model of iPSC-derived Neurons for neurodevelopmental and psychiatric disorders (NPD) (MiNND) aims to generate isogenic hiPSC lines carrying (Loss-of-function) LoF alleles for about 150-200 NPD genes on multiple donor genetic backgrounds. Here, we generated 297 iPSC lines from 6 donor lines (4 females and 2 males) for 66 LoF genes across multiple batches. Transcriptional effect of LoF was assayed using bulk RNA-seq.

UPDATES:
[Aug-10-2026] The cell line "GHI126" was changed to "GHI26".
[Aug-10-2026] Sample GSM9551613 (V3452) was changed from "Negative Control" to "DNMT3A", and GSM9551617 (V3533) was changed from "DNMT3A" to "Negative Control".

first: Jubao

last: Duan

first: Zhiping

last: Pang

first: Hanwen

last: Zhang


title: Context-dependent effect of glucocorticoid receptor activity shapes ovarian cancer cell plasticity and therapy response

city: Baronissi

first: Giovanna

middle: Maria

last: Ventola

state: Salerno

address: Via S. Allende, 43L

country: Italy

institute: Genomix4life s.r.l.

summary: The phenotypic plasticity of cancer cells, i.e. their adaptability to a variable/ stressful environment, is fundamental for disease progression/aggressiveness. Here we revealed that the glucocorticoid receptor (GR, NR3C1), a key player in the human response to stress, controls proliferation, morphology, motility/invasion, and the gene expression profile of high-grade serous ovarian carcinoma (hereafter OC) cells. By modulating glucose metabolism, GR acts as a tumor suppressor delaying ovarian cancer growth under 3D-settings. Conversely, under 2D conditions GR acts as a tumor promoter, driving cell mesenchymalization, increasing cell motility and chemoresistance. Strikingly, modulators of glucose metabolism as metformin and 2-deoxyglucose, are alone sufficient to induce similar cell behavioural changes. So, in ovarian cancer a GR-glucose metabolism axis modulates a escaping signalling response triggered by stressful (3D overgrowth, starvation) condition.

overall_design: SKVO3 cells were infected with lentiviral particles carrying a short hairpin RNAs (shRNA) targeting NR3C1 gene (shNR3C1), and a resistance to puromycin and  an empty vector (shEmpty) used as a control.  RNAseq was performed using (shNR3C1) vs (shEmpty) grown in 2D setting and in spheroids generated by (shNR3C1) vs (shEmpty) grown in 3D setting.

first: Micaela

last: De Girolamo

first: Eduardo

last: Ibello

first: Teresa

last: Improda

first: Ilaria

last: Tedesco

first: Carmela

last: Dell’Aversana

first: Silvia

last: Buonaiuto

first: Salvatore

last: Arbucci

first: Cristina

last: D’Aniello

first: Dario

last: De Cesare

first: Renato

last: Franco

first: Concetta

last: Ambrosino

first: Lucia

last: Altucci

first: Luigi

last: Cobellis

last: Patriarca

first: Gabriella

last: Minchiotti

first: Gilda


title: IgA autoantibodies trigger pro-inflammatory, pro-fibrotic and type I interferon responses in Hidradenitis suppurativa skin lesion

city: Bethesda

first: Kan

last: Jiang

state: MD

address: 9000 Rockville Pike

institute: NIAMS/NIH

summary: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with complex immune dysregulation. While previous studies have reported tertiary lymphoid structures (TLS) and IgA-producing B cells in HS lesions, the pathogenic role of IgA autoantibodies remains poorly understood. Here, we demonstrate that lesional HS skin exhibits elevated expression of IGHA1, IGHA2, and J chain, as confirmed by qPCR, immunofluorescence, and western blot analyses. Single-cell RNA sequencing identified local plasma and B cells as the primary source of IgA. Autoantigen profiling revealed a diverse repertoire of IgA autoantibodies targeting nuclear, cytoplasmic, and membrane antigens, including MDA5, complement C3/C4, NLRP1, and ACE, with levels correlating with disease severity. We identified IgA autoantibodies targeting CD68⁺ macrophages, which induced secretion of TNF, IL-6, and IL-1β, and upregulated inflammasome and fibrotic pathways. Anti-NET IgA was elevated in HS and promoted NET formation, establishing a pathogenic feedback loop. NET–IgA immune complexes activated M2 macrophages to secrete CCL18, driving collagen production by fibroblasts and promoting a type I IFN signature. IgA immune complexes presented by myeloid dendritic cells activated CD4⁺ T cells, triggering IFN-γ production, further amplifying local inflammation. Direct exposure of fibroblasts to NET–IgA complexes triggered expression of adhesion molecules, chemokines, and regulators of adaptive immunity. Together, these findings uncover a novel role for IgA autoantibodies in HS, implicating them as central drivers of chronic inflammation, fibrosis, and immune crosstalk across neutrophils, macrophages, fibroblasts, and T cells.

overall_design: M2 macrophages treated with control IgA or HS IgA purified from skin tissue using protein M, skin fibroblasts incubated with NETs or NET + IgA, or skin fibroblasts incubated with supernatants of macrophages exposed to NETs or NET + IgA

first: Carmelo

last: Carmona-Rivera

first: Liam

last: O’Neil

last: Patino-Martinez

first: William

last: Ambler

first: Mariana

last: Kaplan


title: Age-dependent autophagy impairment risks Alzheimer’s disease due to ULK1 reduction

first: Lipeng

last: Mao

address: No.601, West Huangpu Avenue

department: Department of Microbiology and Immunology

institute: Jinan University

summary: Why age is the primary driver of the most common dementia-Alzheimer’s disease (AD)? Autophagy plays fundamental roles in cellular homeostasis, metabolic energetics, and in maintaining cellular resilience such as via eliminating damaged mitochondria. It is proposed that impaired autophagy leads to compromised catabolic degradation of amyloid beta (Aβ) and Tau pathologies, the disease-defining pathologies of AD; however, molecular mechanisms on whether and if yes, why reduced autophagy during ageing and its contribution to AD, especially in human samples, are largely elusive.   By using serum and CSF samples from a healthy ageing cohort (n = 22 with 4-year follow up samples) and an AD cohort (n = 391), we show that the abundance of ULK1 protein in serum and CSF decreases with increasing age and is extremely lower in AD patients than in age-matched controls.  In a large number of postmortem human brain samples (n = 72), expression of ULK1 in entorhinal cortical and hippocampal neurons in AD patients is significantly lower than in neurons from cognitive normal controls. To investigate whether ULK1 reduction is a bystander or cause/risk of AD, we generated a ubiquitously ULK1-ov mouse model and an AAV-based CA1 neuronal ULK1-ov mouse model in Aβ-bearing background; ULK1 overexpression stimulates autophagic and phagocytic degradation of Aβ, improves mitochondrial quality, thereby delaying progressive cognitive loss. Similarly, in hTau.P301S mice, overexpression of ULK1 inhibits Tau pathology and inhibits memory loss; mechanistically, ULK1 upregulation increases autophagy which increases cellular NAD+, leading to the inhibition of acetylated Tau174 (a cause of Tau pathology) through the NAD+/SIRT1 axis. ULK1 is likely a druggable target for AD as small molecule activators of ULK1 antagonize AD progression which is dependent on PINK1- and FUNDC1-related mitophagy. We propose age-dependent autophagy impairment risks AD due to ULK1 reduction, opening a new window for anti-AD therapeutics.

overall_design: Total RNA was isolated from hippocampal tissues from WT, 5xFAD, 5xFAD;Ulk1OV and Ulk1OV mice. Agarose gel electrophoresis was applied to check RNA integrity and DNA contamination; RNA purity (as well as concentration) was checked by the NanoPhotomerer spectrophotometer (IMPLEN) and Bioanalyzer 2100 system (Agilent Technologies). Then cDNA libraries were constructed using ≥ 800 ng RNA per sample with the Illumina's NEBNext® UltraTM RNA Library Prep Kit following manufacturer’s recommendations. The effective concentration of the library was determined to be at least 2nM. Next-generation sequencing data (performed by the company Novogene, China) were obtained and analyzed. FastQC and trim galore were used to filter raw sequence data and the removal of adapters, N-containing reads, and low-quality reads (reads below Q20).

first: Jun-ping

last: Pan

first: Ping-jie

last: Wang

first: Jianying

last: Zhang

first: Li-peng


title: Adipocytes signal to recruit specific mRNAs from surrounding cells to restore expression deficits [RNA-Seq]

status: Public on Mar 03 2026

city: St. Louis

first: Clair

last: Crewe

address: 660 S Euclid Avenue

institute: Washington Univeristy in St. Louis

summary: Extracellular vesicles (EVs) are nano-sized, membrane-delimited, particles released by cells that carry signaling macromolecules. A major pathway of EV production is potentiated by neutral sphingomyelinase 2 (SMPD3/nSMAse2), an enzyme that generates ceramide from sphingomyelin. In our attempt to study this pathway in adipocytes of male mice, we discovered that the elimination of SMPD3 from adipocytes in vivo triggers a signal to surrounding immune cell-like preadipocytes to release EVs that carry SMPD3 mRNA. This results in a widespread increase in SMPD3 mRNA in purified null adipocytes without a change in the transcripts of other enzymes involved in ceramide metabolism. These results point to a fundamental, novel, and selective mechanism by which specific mRNA molecules are acquired from the microenvironment to a level that can restore expression of mRNA and protein in a cell that is depleted of the corresponding genetic information.

overall_design: After 2 weeks on doxycycline diet to induce SMPD3 knockout, subcutaneous white adipose tissue (sWAT) control and ad-SMPD3KO mice were harvested. sWAT was dissocited with collagenase into single cells and live cells were sorted by FACS.

first: Christy

last: Gliniak

first: Toshiharu

last: Onodera

first: Shiuhwei

last: Chen

first: Jan-Bernd

last: Funcke

first: May-Yun

first: Snigdha

last: Tiash

first: Yun-Ling

last: Pai

first: Marjori

last: Russo

first: Saket

middle: A

last: Patel

first: Ze

last: Yu

first: Yi-Cian

last: Zheng

first: Chao

last: Xing

first: Laurent

last: Gautron

first: Chun-Kan

first: Chen

last: Liu

first: Philipp

last: Scherer


title: Adipocytes signal to recruit specific mRNAs from surrounding cells to restore expression deficits [scRNA-Seq]

first: Clair

last: Wang


title: Clonal dynamics reveal cancer resistance arises from adaptive programs [scRNA-Seq]

city: Philadelphia

first: Yeqing

address: 3601 Spruce Street

institute: The Wistar Institute

summary: Most advanced cancers initially respond to targeted therapies but eventually relapse1. Rather than acquiring new mutations, resistance is driven by drug-tolerant persister cells (DTP) that enter a reversible drug-refractory state and sustain minimal residual disease2. Here, we developed MeRLin, a high-resolution barcoding platform combining single-cell RNA sequencing, RNA fluorescence in situ hybridization, and computational analyses to track clonal and transcriptional dynamics of melanoma cells during targeted therapy. Clonal tracking reveals that dominant resistant clones arise from minor pre-treatment subpopulations. The pre-treatment melanoma populations diversify into phenotypically distinct DTP subpopulations, marked by stress-like, lipid metabolism, PI3K signaling, and extracellular matrix remodeling programs associated with adaptive resistance. Spatial transcriptomics revealed the co-localization of lipid metabolism and PI3K signaling programs near the tumor boundaries, and a complex network of autocrine and paracrine interactions among DTP subpopulations. Using barcoded RNA fluorescence in situ hybridization, we identified a dominant persister subpopulation in resistant tumors marked by SLC2A1 expression. Thus, MeRLin provides a robust framework to dissect melanoma heterogeneity and uncover vulnerabilities in persister populations to improve long-term treatment efficacy.

overall_design: WM4237-1 cells were spinfected with a lentiviral barcode library in the presence of polybrene (8 μg/mL). mNeptune2.5-positive cells were sorted by flow cytometry to ensure a multiplicity of infection (MOI) below 40%. Barcoded cells were then expanded and split into replicate populations, with one aliquot preserved as the original control. Replicates of barcoded WM4237-1 cells or non-barcoded, dissociated WM4007 PDX cells were subcutaneously injected into immunodeficient mice and monitored for tumor growth. Once tumors were established, mice were treated with BRAFi/MEKi, and tumor samples were collected longitudinally throughout treatment until relapse.

first: Haiyin

last: Li

first: Jessica

last: Kaster

first: Maggie

last: Dunne

first: Min

last: Xiao

first: Ling

first: Monzy

last: Thomas

first: Nazifa

last: Promi

first: Dylan

last: Fingerman

first: Gregory

middle: S

last: Brown

first: Xingyue

last: Zhu

first: Meenhard

last: Herlyn


title: TOX3 in hypothalamic POMC-lineage cells regulates energy balance via the PTEN-AKT signaling axis

city: Chengdu

first: Qin

last: Tang

state: Select...

address: 37 Guoxue Xiang, Wuhou District, Chengdu, Sichuan Province, China

institute: West China Hospital of Sichuan University

summary: Obesity and its associated metabolic disorders, including type 2 diabetes and fatty liver disease, represent a growing global health burden. Although the hypothalamus is well-established as the central regulator of energy homeostasis through specialized neuronal circuits, the molecular mechanisms governing these pathways remain incompletely elucidated. In this study, we identify thymocyte selection-associated high mobility group box 3 (TOX3) as a critical metabolic regulator in pro-opiomelanocortin (POMC) neurons of the arcuate nucleus. By employing cell-type-specific genetic manipulation in murine models, we establish that conditional TOX3 ablation in POMC neurons exacerbates diet-induced obesity and metabolic dysfunction, while its overexpression in these neurons confers robust metabolic benefits. Mechanistically, TOX3 enhances POMC neuronal function via a novel post-translational regulatory mechanism involving PTEN proteasomal degradation, leading to potentiated AKT signaling. This central modulation drives sympathetic activation of adipose tissues, resulting in enhanced lipid mobilization and energy expenditure. Notably, TOX3 exhibits striking neuronal specificity, as both loss- and gain-of-function manipulation in agouti-related peptide (AgRP) neurons produce negligible metabolic consequences. Our work identifies previously unrecognized physiological roles of TOX3 in POMC neurons that are essential for maintaining energy homeostasis, thereby revealing novel therapeutic opportunities for metabolic disorders.

overall_design: Hypothalamus from three Pomc-cre;Ai9 or PTKO;Ai9 male mice fed an HFD for 16 weeks were pooled per experimental sample. Single-cell suspensions were prepared using the Adult Brain Dissociation Kit (Miltenyi Biotec, #130-107-677) according to the manufacturer’s instructions. Briefly, freshly dissected hypothalamus was rinsed in ice-cold Dulbecco’s PBS (D-PBS) and subsequently transferred into gentleMACS C Tubes (Miltenyi Biotec, #130-093-237) containing the enzymatic digestion mixture. Tissue dissociation was performed using the gentleMACS Octo Dissociator with Heaters (Miltenyi Biotec, #130-096-427). The resulting cell suspension was filtered through a 70 μm nylon mesh and centrifuged at 300 × g for 10 minutes at 4°C, followed by removal of cellular debris and erythrocytes. The pelleted cells were resuspended in D-PBS, and cell viability was assessed using 7-aminoactinomycin D (7-AAD; Beyotime Biotechnology, #C1053S, Shanghai, China). Fluorescence-activated cell sorting was conducted using a BD FACSAria SORP cell sorter (BD Biosciences) at the Flow Cytometry Core Facility. tdTomato-positive cells were selectively collected for subsequent RNA sequencing analysis, which was performed by Shi-Bio Technology (Wuhan, China).

first: Juan

last: Pang

first: Jinhang

last: Zhang

first: Qinhui

first: Jiahui

first: Ailin

first: Ying

last: Xu

first: Haiying

last: Song

first: Haifeng

last: Zeng

first: Xiandan

last: Jing

last: Yang

first: Yimin

last: Xiong

first: Zijing

first: Yining

first: Yanping

first: Li

last: Mo

first: Jinhan

last: He


title: Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features

status: Public on Mar 02 2026

city: New York

first: Aileen

last: Ugurbil

address: 87 Bedford St, Apt 4

institute: The Rockefeller University

summary: Cancer arises from somatic mutations whose effects are executed through dysregulated gene-regulatory programs that reshape chromatin, transcription, and malignant phenotypes. To uncover gene regulatory principles underlying heterogeneous cancer cell states and their linked environmental features, here we present a pan-cancer single-cell, multi-omic atlas of human cancer cell lines, including a compendium of 240,957 transcriptomes and 223,347 chromatin-accessibility profiles from primary cancers spanning 20 tumor types. We revealed extensive pan-cancer cell-state heterogeneity, core gene-regulatory networks, and consensus epithelial–mesenchymal transition (EMT) trajectories that transcend tissue of origin and are governed by conserved epigenomic and transcriptomic features. In addition, our copy-number variation analysis implicated transcription factor amplification, followed by hyperactive downstream regulation, as a major driver of malignant states. Further focused analysis of acral versus cutaneous melanoma cell lines uncovers a universal inflammation-suppressive program in acral melanoma versus an inflamed regulatory landscape in cutaneous melanoma, highlighting the JAK–STAT axis as a key discriminator. Finally, by integrating single-cell and bulk datasets across models and patient cohorts, we revealed tumor–microenvironment co-adaptation in vivo, and this was associated with immunotherapy responsiveness.

overall_design:
Easy-Sci ATAC Seq and Easy-Sci RNA seq profiling of 60 pooled cancer cell lines across 20 cancer types

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The table below lists SRA accessions for raw data already submitted to SRA under PRJNA1354039.
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first: Zihan

first: Joshua

last: Kwan

first: Chloe

last: Schaefer

first: Abdulraouf

last: Abdulraouf

first: Ziyu

last: Lu

first: Wei

last: Zhou

first: Junyue

last: Cao


title: Cranial placode differentiation defect in individuals born without a nose

status: Public on Mar 01 2026

city: Singapore

first: Vanitha

middle: Venkoba

last: Rao

address: National University of Singapore Department of Biological Sciences  14 Science Drive 4 Block S1A, #05-05

department: Department of Biological Sciences

country: Singapore

institute: National University of Singapore

summary: Bosma arhinia microphthalmia syndrome (BAMS) is a rare congenital disorder characterized by the absence of a nose, along with eye and reproductive anomalies. BAMS is caused by heterozygous missense variants in SMCHD1, an epigenetic regulator. Despite uncovering its genetic basis, the cellular basis of the disease has remained elusive. The embryonic development of the nose involves direct contributions from both the neural crest and cranial placodes. Here we differentiated patient-derived induced pluripotent stem cells towards the cranial placode lineage and found that they exhibited significant differentiation defects. Combined transcriptome and DNA methylome analyses further revealed dysregulation in cell adhesion but without overt apoptosis. Together our research suggests that BAMS is caused by impaired differentiation to cranial placode cells and changes in cell adhesion, offering new insights into the cellular pathology of this enigmatic syndrome.

overall_design: RNA-seq of Cranial Placodal cells (Day 12) differentiated from Control and BAMS patient derived iPSC

last: Venkoba Rao

first: Shifeng

last: Xue


title: Activity-dependent ribosome profiling reveals the landscape of canonical and non-canonical translation in brain tissue [Ribo and RNA-Seq]

city: Wako

first: Nayan

last: Suryawanshi

state: Saitama

address: Hirosawa 2-1

department: Center for Brain Science

country: Japan

institute: RIKEN

summary: Identification hundreds of activity-induced mORFs and uORFs.

overall_design: Ribosome footprints count analysis to indentify novel ORFs using data obtained from RNA-seq (Ribo-seq)

first: Yi-Kai

last: Chen


title: Gene expression profile on a single-cell level of myeloid cells isolated from dura mater, from control mice, and mice infected with group B streptococci

city: Freiburg

first: Vitka

last: Gres

address: Breisacherstraße 115b

department: Institute for Infection Prevention and Control

institute: University of Freiburg

summary: Macrophages and monocytes in dura play a central role in CNS defence against bacteria. Here, we wanted to examine heterogeneity and expression profiles of different myeloid populations in control and streptocicci infected dura.

overall_design: Prior FACS, cells from individual control or infected mice were labelled using the 10X 3' CellPlex Kit Set A (PN-1000261) following manufacturer’s recommendations. CD45+CD11b+ cell population was sorted. In total, 5-6 individual animals per group were pooled after FACS. For controls, around 10 750 cells were sorted per mouse (64 500 cells in total), and for infected mice, in average 11 600 cells were sorted per mouse (46 400 cells in total).

first: Florens

last: Lohrman

first: Vidmante

last: Fuchs

first: Philipp

last: Henneke


title: Role of monocytes and meningeal macrophages in bacterial meningoencephalitis

summary: Macrophages in the dura mater  are substantial contributors to the immune defense of the brain, however, their site-specific origin and function in bacterial infections of the central nervous system are incompletely understood. In a natural model of streptococcal meningoencephalitis, where bacteria systemically spread via the bloodstream to the brain , we found streptococci to be largely restricted in the meninges . Further sporadic spread of bacteria to the underlying brain parenchyma caused a region-restricted microglia activation. Invasion of monocytes, but not granulocytes into brain  and leptomeninges correlated to the disease severity. Inflammation in the dura was accompanied by activation and loss of dural macrophages, and by the rapid engraftment of highly activated monocytes. In addition, monocyte progenitors in the skull marrow underwent drastic changes and acquired a more immature phenotype likely due to infection-induced emergency myelopoiesis.  Notably, while dural monocytes were derived from adjacent skull marrow in a CCR2-independent fashion, the high demand for dural monocytes in streptococcal meningoencephalitis required intact CCR2 signalling and involved the long bone marrow, indicating heterogeneity in monocyte recruitment. Furthermore, meningoencephalitis increased monocyte progeny from monocyte-dendritic cell progenitors compared to the homeostatic, granulocyte-monocyte progenitor-dominated origin. Accordingly, monocytes in the dura, recruited from distinct reservoirs depending on disease-inherent needs, are intertwined with the disease course and may thus offer opportunities for therapeutic interventions.  Macrophages in the dura mater  are substantial contributors to the immune defense of the brain, however, their site-specific origin and function in bacterial infections of the central nervous system are incompletely understood. In a natural model of streptococcal meningoencephalitis, where bacteria systemically spread via the bloodstream to the brain , we found streptococci to be largely restricted in the meninges . Further sporadic spread of bacteria to the underlying brain parenchyma caused a region-restricted microglia activation. Invasion of monocytes, but not granulocytes into brain  and leptomeninges correlated to the disease severity. Inflammation in the dura was accompanied by activation and loss of dural macrophages, and by the rapid engraftment of highly activated monocytes. In addition, monocyte progenitors in the skull marrow underwent drastic changes and acquired a more immature phenotype likely due to infection-induced emergency myelopoiesis.  Notably, while dural monocytes were derived from adjacent skull marrow in a CCR2-independent fashion, the high demand for dural monocytes in streptococcal meningoencephalitis required intact CCR2 signalling and involved the long bone marrow, indicating heterogeneity in monocyte recruitment. Furthermore, meningoencephalitis increased monocyte progeny from monocyte-dendritic cell progenitors compared to the homeostatic, granulocyte-monocyte progenitor-dominated origin. Accordingly, monocytes in the dura, recruited from distinct reservoirs depending on disease-inherent needs, are intertwined with the disease course and may thus offer opportunities for therapeutic interventions.

overall_design: We investigated the transcriptional differences between dural macrophages (DM) and microglia (MG) in control or infected mice 2 days post group B streptococcal (GBS) infection. We used three control and three infected Mrc1CreER;R26Tomato mice that were induced with tamoxifen 8 weeks prior.

last: Lohrmann

first: Lance

last: Pahutan Bosch

first: Anne

last: Lösslein

first: Jana

last: Neuber

first: Zohreh

last: Mansoori Moghadam

first: Tiago

last: Martins

first: Sebastian

last: Baasch

first: Julia

last: Henschel

first: Mirjam

last: Freudenhammer

first: Marco

last: Prinz

first: Katrin

last: Kierdorf

last: Kolter

first: Daniel

last: Erny


title: Single-cell profiling of goose thymus uncovers the developmental program and regulatory logic of T cell differentiation

status: Public on Feb 28 2026

city: shanghai

first: zuoyin

last: zhu

address: number 1239 siping road

institute: tongji university

summary: The thymus is essential for T cell development and the establishment of central tolerance, yet avian thymic development remains poorly characterized. Using the Zhedong White goose as a model, we analyzed thymic development across four stagesby integrating histological analysis with single-cell RNA sequencing. The goose thymus exhibits a multilobulated architecture, undergoes rapid post-hatch maturation, and shows stage-dependent involution. Single-cell analysis identified the major thymic cell populations, with T cells predominating and γδ T cells present at higher proportions than in mammals. Pseudotime analysis revealed double-positive (DP) cells as a central differentiation hub. Double-negative (DN) thymocytes progressed from DN1 to DN3b through a stepwise program characterized by lineage commitment marked by upregulation of BCL11B, NOTCH1, and TCF7, followed by induction of β-selection–associated genes, including RAG1/2 and DNTT. Thymic epithelial cells functioned as a major signaling hub, with adhesion- and microenvironment-related pathways coordinating TEC–T cell interactions, while DP and mature T cells progressively emerged as key signal integration nodes. Cross-species comparison indicated an overall conserved developmental framework, with the most pronounced species-specific differences observed at the DP stage. Collectively, this study systematically delineates the developmental trajectories of thymic T cells and their microenvironmental regulation in the goose, providing a valuable resource for studies of avian immune development and comparative immunology.

overall_design: To systematically characterize thymic T-cell development in avian species, this study profiled thymic cell populations of female Zhedong White (ZW) geese across four key developmental stages: embryonic day 25 (E25d), post-hatch day 14 (D14), day 70 (D70), and day 200 (D200), corresponding to embryonic thymus formation, early postnatal establishment of immune function, formation of immune homeostasis after sexual maturity, and maintenance of immunity during the laying period, respectively. For single-cell RNA sequencing, thymic tissues were collected from three biologically independent female geese at each developmental stage and pooled to generate one scRNA-seq sample per stage. Thus, each sequencing library represents a pooled biological replicate composed of thymocytes derived from three different individuals at the same developmental stage. To ensure anatomical consistency across samples, the first pair of thymic lobes adjacent to the head was consistently collected from each goose, as the avian thymus is bilaterally distributed along the neck and typically consists of multiple lobes per side. Fresh thymic tissues were preserved in MACS Tissue Storage Solution prior to dissociation, and thymocytes were isolated under sterile conditions for single-cell library preparation and sequencing. In parallel, thymuses from eight additional female geese per stage were used for histological and morphological analyses. Sex was confirmed by PCR amplification of the CHD-1 gene. All animal procedures were approved by the Animal Protection Committee of the Shanghai Academy of Agricultural Sciences (Approval No. SAAS-SL-2023021).

first: Zhu

last: Zuoyin

first: Wang

last: Cui

first: Yu

last: Yong


title: Transcriptional and functional profiles of muscarinic cholinergic receptor-expressing neurons in the primate prefrontal cortex

city: Boston

first: Single Cell

last: Sequencing Core

address: 72 E. Concord St

institute: BU Single Cell Sequencing Core

summary: Acetylcholine modulates the anterior cingulate (ACC) and lateral prefrontal (LPFC) cortices via specific m1-m4 muscarinic receptor subtypes (mAChR) encoded by CHRM1-4 genes. Single-nucleus RNA sequencing and mRNA-protein histology in macaques revealed CHRM3 as the most enriched mAChR gene in neurons, while m1 predominates at the protein level, likely due to nuclear retention of CHRM3 and cytoplasmic trafficking of CHRM1. CHRM3 and CHRM1 showed strong co-expression and functional overlap, differing from CHRM2 mainly in calcium signaling-related genes. CHRM2 is uniquely enriched in deep layer excitatory and PVALB+ inhibitory neurons. Although CHRM+ cell distributions are similar between areas, CHRM1–3+ excitatory neurons in ACC exhibited upregulation of synaptic plasticity genes. Functional in vitro experiments confirm a more robust cholinergic-mediated decrease in excitatory:inhibitory synaptic ratio in ACC than in LPFC neurons, accompanied by compensatory changes in spine morphology. These findings highlight region-specific acetylcholine signaling essential for flexible processing, learning and memory.

overall_design: snRNA-seq of ACC and LPFC tissue from 4 adult male rhesus monkeys (Macaca mulatta; ages= 8.5, 8.9, 20.8, 24.8 y.o.)