A5072002953- Acute Myeloid Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Hematological disorders and diagnostics
- Single-cell and spatial transcriptomics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Hematopoietic Stem Cell Transplantation
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Medical Imaging and Pathology Studies
- Lung Cancer Treatments and Mutations
- Immune Cell Function and Interaction
- Molecular Biology Techniques and Applications
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Advanced Biosensing Techniques and Applications
- Mitochondrial Function and Pathology
- Cancer Mechanisms and Therapy
- RNA Research and Splicing
- Chronic Lymphocytic Leukemia Research
- Acute Lymphoblastic Leukemia research
- Genetic Mapping and Diversity in Plants and Animals
Fudan University
2023-2025
Ningbo University
2025
MRC Weatherall Institute of Molecular Medicine
2021-2024
University of Oxford
2021-2024
Medical Research Council
2021-2024
Oxford BioMedica (United Kingdom)
2022-2023
Science Oxford
2023
Abstract A lack of models that recapitulate the complexity human bone marrow has hampered mechanistic studies normal and malignant hematopoiesis validation novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, hematopoietic lineages. These 3D structures capture key features marrow—stroma, lumen-forming sinusoids, myeloid including proplatelet-forming...
Genotype-phenotype correlations are revealed by bone marrow single-cell RNA sequencing in Diamond-Blackfan anemia.
Myeloproliferative neoplasms are stem cell-driven cancers associated with a large burden of morbidity and mortality. Most patients present early-stage disease, but substantial proportion progress to myelofibrosis or secondary leukemia, advanced poor prognosis high symptom burden. Currently, it remains difficult predict progression, therapies that reliably prevent reverse fibrosis lacking. A major bottleneck the discovery disease-modifying has been an incomplete understanding interplay...
Juvenile myelomonocytic leukemia (JMML) is a poor-prognosis childhood usually caused by RAS-pathway mutations. The cellular hierarchy in JMML poorly characterized, including the identity of stem cells (LSCs). FACS and single-cell RNA sequencing reveal marked heterogeneity hematopoietic stem/progenitor (HSPCs), an aberrant Lin−CD34+CD38−CD90+CD45RA+ population. Single-cell HSPC index-sorting clonogenic assays show that (1) all somatic mutations can be backtracked to phenotypic HSC...
Abstract Maternal overnutrition during lactation predisposes offspring to develop metabolic diseases and exacerbates the relevant syndromes in males more than females later life. The hypothalamus is a heterogenous brain region that regulates energy balance. Here we combined trait quantification of mother mice under low high fat diet (HFD) feeding lactation, with single nucleus transcriptomic profiling their at peak lacation understand cellular molecular alterations response maternal dietary...
Single-nucleus RNA sequencing (snRNA-seq) has emerged as a powerful approach for studying cellular heterogeneity in metabolic tissues. However, snRNA-seq analysis remains challenging due to low gene expression and data complexity. Here, we introduce an optimized upstream analytical workflow from 67 samples across white adipose tissue, muscle, liver the hypothalamus. We emphasized importance of key steps including ambient removal, doublet identification integration ensure accurate downstream...
Triptans are a class of commonly prescribed antimigraine drugs. Here, we report previously unrecognized role for them to suppress appetite in mice. In particular, frovatriptan treatment reduces food intake and body weight diet-induced obese Moreover, the anorectic effect depends on serotonin (5-HT) 1B receptor (Htr1b). By ablating Htr1b four different brain regions, demonstrate that engages spatiotemporally segregated neural pathways regulate postnatal growth intake. AgRP neurons arcuate...
Abstract Myeloproliferative neoplasms are stem cell-driven cancers associated with a large burden of morbidity and mortality. The majority patients present early-stage disease, but substantial proportion progress to myelofibrosis and/or secondary leukemia, advanced poor prognosis high symptom burden. Currently, it remains difficult predict progression, we lack therapies that reliably prevent or reverse fibrosis development. A major bottleneck the discovery disease-modifying has been an...
Abstract A lack of models that recapitulate the complexity human bone marrow has hampered mechanistic studies normal and malignant hematopoiesis validation novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from iPSCs committed to mesenchymal, endothelial hematopoietic lineages. These 3-dimensional structures capture key features - stroma, lumen-forming sinusoidal vessels myeloid cells including pro-platelet forming...
Abstract Hypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival under limited oxygen (hypoxia) and frequently activated within malignancy. Malignant context affects the role of HIFs oncogenesis; however, mechanisms regulating HIF context-specificities not well characterised. Applying JAK2V617F (JVF) model myeloproliferative neoplasms (MPNs), in which HIF-1 is active normoxia (20% O 2 ), we sought determine whether modality activation directs its...
Infant ALL (iALL) is initiated in utero, most often by rearrangement of the KMT2A gene (KMT2Ar). It carries a very poor prognosis despite lack additional oncogenic driver mutations common childhood ALL. Here, we aimed to identify specific properties human fetal hematopoietic stem/progenitor cells (HSPC) that promote leukemic transformation KMT2Ar iALL using molecular, functional and vivo assays. First, comparing transcriptomes HSPC adult derived fetal-specific signature identified oncogene...
<div>Abstract<p>A lack of models that recapitulate the complexity human bone marrow has hampered mechanistic studies normal and malignant hematopoiesis validation novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, hematopoietic lineages. These 3D structures capture key features marrow—stroma, lumen-forming sinusoids, myeloid including...
<p>MM ALL Donor Details</p>
<p>Supplementary Materials and Methods, Supplementary Figures S1-S12</p>
<p>Supplementary Materials and Methods, Supplementary Figures S1-S12</p>
<p>Supplementary Table 7 NGS Panel</p>
<p>MM ALL Donor Details</p>
<p>Supplementary Table 2 Gene sets for GSEA</p>
<p>Supplementary Table 3 HD and MPN samples.</p>
<p>Supplementary Table 1 VEGFAC Top Differentially Expressed Genes by Cluster</p>
<p>Supplementary Table 1 VEGFAC Top Differentially Expressed Genes by Cluster</p>