title: Cell fate reprogramming of erythroid cells caused by reduction of H3K4me3 lead to a “retrograde manner” leukemia genesis [scRNA-seq_mouse]

city: zhengzhou

first: Hengchao

last: Zhang

state: Henan

address: 河南省郑州市高新技术开发区科学大道100号郑州大学新校区

institute: zzu

summary: While it's established that methionine metabolism, can impact histone methylation to have a direct role in influencing cell fate determination, methionine metabolic regulation of hematopoietic stem cell commitment and erythroid differentiation is unknown. Here, we investigated how AHCY, an important enzyme in themethionine cycle and timely hydrolysis to sustain methylation reactions, regulates cell fate reprogrammingon in vitro and in vivo. Firstly, we observed that depletion or targeted pharmacological inhibition of AHCY in erythrocytes markedly inhibites cell proliferation, induces cell apoptosis and causes the appearance of other lineage cells. In addition, we applied single-cell sequencing to adherent and suspended cells and identified multiple cell populations, including stem/progenitor cells such as HSC, megakaryocyte/erythroid progenitor cells (MEP), common myeloid progenitor cells (CMP), and granulocyte monocyte progenitor cells (GMP), as well as immune cells such as macrophages and myeloid dendritic cells (mDC). We engrafted adherent and suspended cells into NCG-c-kit-Cas9-TM mice without irradiation. After 4 weeks and 12 weeks postengraftment, we observed human cell chimerism in marrow, peripheral blood and spleen. Importantly, we further found that AHCY-mediated histone methylation rather than DNA methylation leading to cell dedifferentiation including H3K4me3, H3K9me3, H3K27me3, H3K36me2 and H3K79me2 modifications. However, consistent phenotype can be observed only after specific inhibiting H3K4me3 on the terminal erythropoiesis. Integrating CUT&Tag sequencing and RNA-seq analysis revealed that expression of transcription factors(TFs), including those lineage-specific TFs (GATA2, CEBPA), are upregulated in dedifferentiation cells, and erythrocyte lineage-specific TFs (GATA1, KLF1) are significantly downregulated. Because AHCY gene expression was significantly lower in terminal erythroid cells of AML patients compared to healthy individuals, clinically, we next detected relatively low levels of H3K4me3 in erythroblasts from bone marrow of some leukemia patients. Colony formation detection was performed on these erythroblasts in vitro using modified semisolid clonal culture, and multiple CFU colony formation could be observed through morphological verification of colony types. These results reveal a previously unappreciated mechanism of methionine metabolism regulating erythropoiesis by affecting methylation modification. All these findings also reveal that histone methylation landscape reshapes the cell fate decision during human erythropoiesis. And we have demonstrated for the first time that the reduction of H3K4me3 leads to the occurrence of "retrograde" leukemia.

overall_design: We intravenously injected 2.5 × 10^5 human Day11 CD34+ cells treated with 0.2 μM DZNep into the tail vein of NCG-c-kit-Cas9-TM 8- to 10-week-old mice, induced Day11 CD34+ cells as negative control and Day0 CD34+ cells as positive control. At 4 and 12 week, bone marrow, spleen and peripheral blood was analyzed via flow cytometry for the presence of human and mouse blood cell surface proteins.

first: Lei

first: Mengjia

first: Lixiang

last: Chen


title: Gene expression profile at single cell level of murine colon organoids harbouring colorectal cancer-associated driver mutations [scRNA-seq]

status: Public on Jun 01 2026

city: Oxford, Oxfordshire

first: Xin

last: Lu

address: Roosevelt Drive

country: United Kingdom

institute: Ludwig Institute for Cancer Research, University of Oxford

type: Expression profiling by high throughput sequencing

summary: We used scRNA-seq to analyse the influence of colorectal-cancer associated driver mutations on the gene expression of colon organoids.

overall_design: Following dissociation, a 5’ workflow (Chromium Single Cell Immune Profiling, Solution v1.1, 10x Genomics) was used to collect scRNA-seq data from the murine wild type and mutant fluorescent colon organoids. Dimensionality reduction, clustering, and differential expression were subsequently conducted in order to assess the differences in their gene expression profiles.

first: Brittany-Amber

last: Jacobs

first: Thomas

middle: M

last: Carroll

first: Felix

last: Zhou

first: Joseph

last: Chadwick


title: P2X4 Drives Sex-Specific Neuroprotection in Autoimmune Neuroinflammation

status: Public on Mar 14 2026

city: Leioa

first: Maria

last: Domercq

state: Bizkaia

address: Barrio Sarriena, s/n

department: Neurosciences

country: Spain

institute: Achucarro Basque Center for Neuroscience

summary: Microglia critically influence multiple sclerosis (MS) pathophysiology through debris clearance, myelin repair, and modulation of neuroinflammation. These processes are partly regulated by ATP-gated ion channel P2X4, predominantly expressed in microglia. We previously reported that ivermectin (IVM), a positive allosteric modulator of P2X4, promotes myelin phagocytosis, remyelination, and functional recovery in experimental autoimmune encephalomyelitis (EAE). Here, we dissected the cellular basis of P2X4-mediated effects using P2X4mCherryIN knock-in (P2X4KI) mice, in which P2X4 is replaced by a non-internalized variant (P2X4KI), leading to increased surface localization at the plasma membrane. Constitutive and myeloid-specific P2X4KI (Cd11b-P2X4KI) mice showed significant amelioration of EAE motor deficits, although exclusively in females. Despite equivalent P2X4 expression, function, and IVM responsiveness between sexes, progesterone potentiated P2X4 currents and prolonged channel deactivation, revealing direct hormonal modulation of P2X4 gating. Notably, ovariectomy abolished P2X4-mediated protection in females, confirming the requirement of female hormones. These findings identify microglial P2X4 as a critical modulator of neuroinflammatory outcomes and uncover a previously unrecognized hormone–P2X4 interaction that underlies sex-specific disease modulation. Targeting this pathway may enable precision therapies for MS.

overall_design: RNA-seq was performed on total microglial populations, isolated by fluorescence-activated cell sorting (FACS), from spinal cords of WildType and Cd11b-P2X4KI mice

first: Paloma

last: Mata

first: Marina

last: Bosch-Juan

first: Eric

last: Bué-Grabot


title: Performance differences in spatial transcriptomics platforms identify Treg biology in human inflammatory bowel disease [Xenium]

status: Public on Mar 13 2026

city: Chicago

first: Parambir

last: Dulai

state: IL

address: 259 E Erie St Ste 1600

country: USA

institute: Northwestern University

summary: Spatial transcriptomics is a rapidly growing field with the potential to enhance our ability to uncover novel biology, support drug development, and guide biomarker discovery. However, a biologically validated comparison of leading single-cell-level spatial transcriptomics platforms to guide scientists is lacking in the field. Using intestinal biopsies (n = 40) from patients with inflammatory bowel disease (IBD) of varying disease states and disease locations and non-diseased controls, we systematically compared two imaging based spatial transcriptomics platforms (CosMx and Xenium) to guide translational work for two NIDDK supported IBD consortiums and the Crohn’s and Colitis Foundation Plexus Biorepository.  In vitro experiments were conducted to validate key biologic findings. We present a comprehensive data resource of over 1.5 million spatially profiled intestinal cells from healthy and IBD samples. We observed CosMx to have overall better data quality than Xenium in both ulcerative colitis and Crohn’s disease across the full spectrum of commercially available panels. The performance of Xenium, but not CosMx, was significantly influenced by block quality and panel size, with a decline in data quality as the panel size increased. We demonstrate operational feasibility for CosMx in multi-center studies, and CosMx uniquely identified Treg-associated biology in both ulcerative colitis and Crohn’s disease which was validated by in vitro experiments. This study highlights the performance differences between CosMx and Xenium, demonstrating the strengths of CosMx for biology discovery in IBD research. Further studies are needed to explore the broader applicability of CosMx in other gastrointestinal conditions.

overall_design: 16 Xenium multi-tissue 337 panel (Ileum_CD_Inflamed: 2, Ileum_CD_NonInflamed: 2, Ileum_UC_NonInflamed: 2, Rectum_CD_Noninflamed: 2, Rectum_CD_inflamed: 2, Rectum_UC_inflamed: 4, Rectum_UC_Noninflamed: 2); 4 Xenium multi-tissue 377 panel with segmentation (Rectum_HC:1, Rectum_UC_nonInflamed: 1, Rectum_UC_inflamed: 2); 4 Xenium multi-tissue 377 panel without segmentation (Rectum_HC:1, Rectum_UC_nonInflamed: 1, Rectum_UC_inflamed: 2); 4 Xenium colon-specific panel (Rectum_HC:1, Rectum_UC_nonInflamed: 1, Rectum_UC_inflamed: 2); 4 Xenium 5K panel (Rectum_HC:1, Rectum_UC_nonInflamed: 1, Rectum_UC_inflamed: 2)

first: Yiming

last: Li

first: Wenjing

last: Yang

first: Hai

last: Wang

first: Alan

last: Robinson

first: Tianming

last: Yu

first: Jenny

middle: Y

last: Ding

first: Cenfu

last: Wei

first: Stephen

middle: B

last: Hanauer

first: Emanuelle

last: Bellaguarda

first: Laura

last: Yun

first: Ronen

last: Sumagin

first: Guang-Yu

first: James

middle: D

last: Lewis

first: Deyu

last: Fang

first: Yingzi

last: Cong

first: Yuan

last: Luo

middle: S