Project description:Purpose: The goal of this study is to decipher the molecular basis of TBLR1-RARa-expressing APL and to explore potential treatment target based on NGS-derived transcriptome profiling (RNA-seq) Methods: RNA-seq was performed to analyze differential gene expression between GFP+ cells from BM of TBLR1-RARa mice (TR1 and TR9) and lin- cells from BM of control mice (Control). Results: Transcriptome profiling associates with leukemic phenotype and predicts HDACi response in TR-induced APL. Conclusions: Our study represents the first bioinformatic analysis of DEGs from APL mice with TBLR1-RARa fusion gene, generated by RNA-seq technology. Transcriptome profiling associates with leukemic phenotype of differentiation block and predicts drug response to HDAC inhibitors.
Project description:We performed a single-cell transcriptomic analysis of monocyte and monocyte progenitors by single-cell mRNA sequencing (scRNA-seq) using the C1 Fluidigm platform. We sorted BM cMoPs (Lin−CD117+CD115+CD135−Ly6C+), BM Ly6C+ monocytes (Lin−CD117-CD115+CD135−Ly6C+) and blood Ly6Chi monocytes (CD115+CD11b+Ly6Chi) from wild-type (WT) C57BL/6 mice by fluorescence-activated cell sorting (FACS) and generated transcriptional profiles for each individual cell (n = 38 for blood Ly6Chi monocytes, n = 66 for BM cMoPs, n = 57 for BM Ly6C+ monocytes).
Project description:Bulk RNA-seq was performed on murine Lin-Sca+Kit+ bone marrow cells from a transgenic SCLtTA/BCR-ABL (DTG) mouse BM cells (CD45.2) to understand the molecular consequences of BCR-ABL1 expression on the global mRNA programme of these cells.
Project description:Lung group 2 innate lymphoid cells (ILC2s) drive allergic inflammation and promote tissue repair. ILC2 development is dependent on the transcription factor retinoic acid receptor-related orphan receptor (ROR?), which is also expressed in common ILC progenitors. To elucidate the developmental pathways of lung ILC2s, we generated ROR? lineage tracer mice and performed single-cell RNA sequencing, flow cytometry, and functional analyses. In adult mouse lungs, we found an IL-18R?+ST2- population different from conventional IL-18R?-ST2+ ILC2s. The former was GATA-3intTcf7EGFP+Kit+, produced few cytokines, and differentiated into multiple ILC lineages in vivo and in vitro. In neonatal mouse lungs, three ILC populations were identified, namely an ILC progenitor population similar to that in adult lungs and two distinct effector ILC2 subsets that differentially produced type 2 cytokines and amphiregulin. Lung ILC progenitors might actively contribute to ILC-poiesis in neonatal and inflamed adult lungs. In addition, neonatal lung ILC2s include distinct proinflammatory and tissue-repairing subsets.
Project description:To better understand how lung neutrophils transcriptionally differ from other tissue neutrophils, we performed single-cell RNA sequencing (scRNA-seq) on BM, PB and lung neutrophils isolated from naïve (BALBc/J) and 4T1 tumor-bearing mice.
Project description:We identified that synergistic and inducible expression of Runx1 and Hoxa9 in pluripotent stem cells gave rise to engraftable iHPC capable of developing into mature ILCs in the Rag2-/-Il2rg-/- recipients. We performed single-cell RNA-seq on the entire regenerative CD45.2+GFP+Lin-CD127+ R9-ILC population from the intestine of Rag2-/-Il2rg-/- recipient mice and the CD45.2+Lin-CD127+ WT-ILC population from the intestine of wild type mice (C57BL/6, CD45.2). Single-cell transcriptome illustrated the transcriptome landscape of the R9-ILCs and wild type ILCs including ILC1, ILC2 and ILC3.
Project description:Brain metastasis (BM) can affect up to 25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been fairly disappointing. Small non-coding microRNAs (miRNAs) regulate the expression of target mRNAs by repressing their translation or regulating their sequence-specific degradation. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which makes them a powerful tool to be exploited for early detection of disease, risk assessment, and prognosis. In this study, we investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from patients with BM (BM+) and without BM (BM-). miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM- patients. Gene expression analysis comparing NSCLC parental and stably transfected miR-328 cells identified several significantly differentially-expressed genes, whose expression may be directly or indirectly regulated by miR-328.
