Project description:NUP98-PHF23 is oncogenic and results in a Hoxa/b + Meis1 overexpression in NP23 leukemias and in premalignant (clinically healthy) hematopoietic tissues. Gene expression profiles from AML, pre-T LBL and B-ALL were compared to wild type bone marrow, thymus and spleen tissues respectively. Similarly, gene expression profiles from premalignant (clinically healthy) NP23 bone marrow, thymus and spleen were compared to wild type bone marrow, thymus and spleen tissues respectively. 106A and 748T lymphoblastic cell lines were compared to wild type thymic tissue.
Project description:We used scRNA seq to analyze mice organ cells (liver, spleen, thymus and bone marrow) as well as neonatal thymus organ cultures that were treated cytokines IL-12 and IL-18.
Project description:Dendritic cells (DC) form a collection of antigen-presenting cells that are distributed throughout the body. Conventional DC (cDC) which include the cDC1 and cDC2 subsets, and plasmacytoid DC (pDC) constitute the two major ontogenically distinct DC populations. The pDC complete their differentiation in bone-marrow (BM) while the cDC subsets derive from pre-committed bone-marrow (BM) precursors, the pre-cDC, that seed lymphoid and non-lymphoid tissues where they further differentiate into mature cDC1 and cDC2. Within different tissues, cDC express distinct phenotype and function. Notably cDC in the thymus are exquisitely efficient at processing and presenting antigens in the class II pathway, while in the spleen they do so only upon maturation induced by danger signals. To appraise this functional heterogeneity, we examined the regulation of the expression of distinct antigen-processing enzymes during DC ontogeny. We analyzed the expression of cathepsin S (CTSS), cathepsin L (CTSL) and thymus specific serine protease (TSSP), three major antigen-processing enzymes regulating class II presentation in cDC, by DC BM precursors and immature and mature cDC from spleen and thymus. We found that pre-cDC in the BM express relatively high levels of these different proteases. Then, their expression is modulated in a tissue-specific and subset–specific manner with immature and mature thymic cDC expressing overall higher levels than immature splenic cDC. On the other hand, TSSP expression level is selectively down-regulated in spleen pDC while CTSS and CTSL are both increased in thymic and splenic pDC. Hence tissue-specific factors program the expression levels of these different proteases during DC differentiation thus conferring tissue-specific function to the different DC subsets.
Project description:Gene expression profiling was performed of Pax5 wild type bone marrow subsets from common lymphoid progenitors through to Hardy stage F cells. These cells were obtained by flow sorting of bone marrow.
Project description:We identified a new type of bone marrow progenitors termed early innate lymphoid cell progenitor (EILP) using TCF-1 GFP reporter mice. We compared the transcriptomes of early innate lymphoid cell progenitors (EILP) with other early progenitors, including HSC, LMPP, CMP, CLP, ETP and DN3.
Project description:Innate lymphoid cells (ILCs) are important regulators in various immune responses. Current paradigm states that all newly-made ILCs originate from common lymphoid progenitors (CLP) in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Unexpectedly, we found that ectopically expressing Id1 or deleting two E protein genes in the thymus drastically increased ILC2 counts in the thymus and other organs where ILC2 normally reside. Further evidence suggests a thymic origin of these mutant ILC2s. The mutant mice exhibit augmented spontaneous infiltration of eosinophils and heightened responses to papain in the lung and increased ability to expulse the helminth parasite, Nippostrongylus brasiliensis. These results prompt the question whether the thymus naturally has the capacity to produce ILC2s and E proteins restrain such a potential. The abundance of ILC2s in Id1 transgenic mice also offers a unique opportunity for testing the biological functions of ILC2s.
Project description:Gene expression profiling was performed of Pax5 wild type bone marrow subsets from common lymphoid progenitors through to Hardy stage F cells. These cells were obtained by flow sorting of bone marrow. Gene expression profiling was performed on 41 samples of RNA extracted from flow sorted B cell precursor populations from common lymphoid progenitor (CLP) through to Hardy stage F. Note that several of the genes expressed in normal mouse B cell progenitors are also involved by deletion/mutation in hypodiploid ALL. Related hypodiploid ALL studies: Gene expression data: GEO GSE27237 SNP & Sequencing data: dbGaP phs000341.v1.p1
Project description:Mononuclear phagocytes and their myeloid progenitors are critical in various homeostatic processes as well as immune responses. We employed single-cell RNA sequencing to investigate myeloid progenitors and mononuclear phagocytic cell subsets, including monocytes, splenic red pulp macrophages and dendritic cells in the spleen and in the bone marrow, with a focus on how Notch2 and its nuclear mediator Rbpj regulate these subsets. Our study offers a comparative analysis of mononuclear phagocytes and their progenitors examining cells isolated from the spleens or bone marrow of myeloid Notch2 (N2ΔCx3cr1)-, and Rbpj (RbpjΔCx3cr1)-deficient mice or control animals. Our findings may provide further insights into the heterogeneity of the mononuclear phagocytic cells in the spleen and bone marrow and show the critical role of Notch signaling in their development.
Project description:Survey of gene expression in 9 types of C57/Bl mouse wild type tissue. RNA was extracted from homogenized whole organs/tissues and include brain, spleen, liver, thymus, kidney, lung, testes, bone marrow, and lymph node. 8 week old male littermate C57/Bl mice