Transcriptomic analysis (RNA-seq) of Lin- BM cells from wild type C57 BM mice and GFP+ BM cells from TBLR1-RARa mice
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ABSTRACT:
PROVIDER: PRJNA728957 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14509918.fastq.gz | Fastqsanger.gz | |||
| SRR14509919.fastq.gz | Fastqsanger.gz | |||
| SRR14509920.fastq.gz | Fastqsanger.gz |
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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.
2021-06-08 | GSE174247 | GEO
Project description:Because PML-RARA-positive acute promyelocytic leukemia (APL) is a morphologically differentiated leukemia, much speculation has been made about whether its leukemic cell of origin might be committed myeloid precursor (e.g., a promyelocyte) vs. a hematopoietic stem/progenitor cell (HSPC). We originally targeted PML-RARA expression with CTSG regulatory elements, based on the early observation that this gene was maximally expressed in cells with promyelocyte morphology. Here, we show that both Ctsg and PML-RARA targeted to the Ctsg locus (in Ctsg-PML-RARA mice) are detected in the purified KLS cells of these mice (Kit+Lin-Sca+ cells, which are highly enriched for HSPCs), and this expression results in biological effects in multi-lineage competitive repopulation assays. Although PML-RARA is indeed expressed at high levels in the promyelocytes of Ctsg-PML-RARA mice, it does not significantly alter the transcriptional signature of these cells, or induce their self-renewal. In sum, these results suggest that in murine models, PML-RARA acts primarily to affect the function of multi-potent progenitor cells, rather than promyelocytes. Since PML/Pml is normally expressed in the HSPCs of both humans and mice, and since some human APL samples contain TCR rearrangements and express T lineage genes, we suggest that the very early hematopoietic expression of PML-RARA in our mouse model may closely mimic the physiologic expression pattern of PML-RARA in human APL patients.
2012-08-14 | GSE40022 | GEO
Project description:Because PML-RARA-positive acute promyelocytic leukemia (APL) is a morphologically differentiated leukemia, much speculation has been made about whether its leukemic cell of origin might be committed myeloid precursor (e.g., a promyelocyte) vs. a hematopoietic stem/progenitor cell (HSPC). We originally targeted PML-RARA expression with CTSG regulatory elements, based on the early observation that this gene was maximally expressed in cells with promyelocyte morphology. Here, we show that both Ctsg and PML-RARA targeted to the Ctsg locus (in Ctsg-PML-RARA mice) are detected in the purified KLS cells of these mice (Kit+Lin-Sca+ cells, which are highly enriched for HSPCs), and this expression results in biological effects in multi-lineage competitive repopulation assays. Although PML-RARA is indeed expressed at high levels in the promyelocytes of Ctsg-PML-RARA mice, it does not significantly alter the transcriptional signature of these cells, or induce their self-renewal. In sum, these results suggest that in murine models, PML-RARA acts primarily to affect the function of multi-potent progenitor cells, rather than promyelocytes. Since PML/Pml is normally expressed in the HSPCs of both humans and mice, and since some human APL samples contain TCR rearrangements and express T lineage genes, we suggest that the very early hematopoietic expression of PML-RARA in our mouse model may closely mimic the physiologic expression pattern of PML-RARA in human APL patients. Bone marrow from individual mice expressing PML-RARA from the murine Ctg locus (mCG-PR) and littermate controls was harvested from both femurs and tibia. Standard cell lysis was performed, and total RNA was extracted from the cells and analyzed using the Affymetrix Mouse Exon 1.0 ST platform.
2012-08-13 | E-GEOD-40022 | biostudies-arrayexpress
Project description:Scrna-Seq was performed on BM Lin- CD127+ cells
2023-01-18 | GSE193835 | GEO
Project description:RARA haploinsufficiency is an invariable consequence of t(15;17) reciprocal translocations in acute promyelocytic leukemia (APL). Furthermore, retinoids and RARA activity have been implicated in hematopoietic self-renewal, lineage commitment and neutrophil maturation. We and others therefore predicted that RARA haploinsufficiency would contribute to APL pathogenesis. To test this hypothesis we crossed RARA+/- mice with mice expressing PML-RARA from the Cathepsin G locus (mCG-PR). We found that RARA haploinsufficiency cooperated with PML-RARA, only modestly influencing the pre-leukemic and leukemic phenotype. Bone marrow from mCG-PR+/- x RARA+/- mice had decreased numbers of mature myeloid cells, increased ex vivo myeloid cell proliferation and an increased competitive advantage following transplantation. RARA haploinsufficiency did not alter mCG-PR dependent leukemic latency or penetrance, but did influence the distribution of leukemic cells; mCG-PR+/- x RARA+/- mice presented more commonly with low to normal white blood cell counts and with myeloid infiltration of lymph nodes. APL arising in these mice was responsive to ATRA, and had virtually no differences in expression profiling compared to tumors arising in mCG-PR+/- x RARA+/+ mice. These phenotypes were dependent on PML-RARA activity, since they were not detected in RARA+/- mice in the absence of the mCG-PR transgene. These data show that RARA haploinsufficiency (like PML haploinsufficiency and RARA-PML) can cooperate with PML-RARA to influence the pathogenesis and phenotype of APL in mice, but that PML-RARA is the driver of t(15;17) APL.
2010-07-29 | GSE23291 | GEO
Project description:RARA haploinsufficiency is an invariable consequence of t(15;17) reciprocal translocations in acute promyelocytic leukemia (APL). Furthermore, retinoids and RARA activity have been implicated in hematopoietic self-renewal, lineage commitment and neutrophil maturation. We and others therefore predicted that RARA haploinsufficiency would contribute to APL pathogenesis. To test this hypothesis we crossed RARA+/- mice with mice expressing PML-RARA from the Cathepsin G locus (mCG-PR). We found that RARA haploinsufficiency cooperated with PML-RARA, only modestly influencing the pre-leukemic and leukemic phenotype. Bone marrow from mCG-PR+/- x RARA+/- mice had decreased numbers of mature myeloid cells, increased ex vivo myeloid cell proliferation and an increased competitive advantage following transplantation. RARA haploinsufficiency did not alter mCG-PR dependent leukemic latency or penetrance, but did influence the distribution of leukemic cells; mCG-PR+/- x RARA+/- mice presented more commonly with low to normal white blood cell counts and with myeloid infiltration of lymph nodes. APL arising in these mice was responsive to ATRA, and had virtually no differences in expression profiling compared to tumors arising in mCG-PR+/- x RARA+/+ mice. These phenotypes were dependent on PML-RARA activity, since they were not detected in RARA+/- mice in the absence of the mCG-PR transgene. These data show that RARA haploinsufficiency (like PML haploinsufficiency and RARA-PML) can cooperate with PML-RARA to influence the pathogenesis and phenotype of APL in mice, but that PML-RARA is the driver of t(15;17) APL. RARA+/- mice were crossed with mice expressing PML-RARA from Cathepsin G locus (mCG-PR). Five leukemic mice were chosen from each of the mCG-PR+/-RARA+/- and mCG-PR+/-RARA+/+ strains and total RNA extracted from the spleen samples were analyzed using Affymetrics Mouse Exon 1.0 platform
2010-07-29 | E-GEOD-23291 | biostudies-arrayexpress
Project description:Profile of gene expression of lungs from ovalbumen sensitized and challenged C57 mice. Keywords: parallel sample
2003-06-10 | GSE447 | GEO
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Project description:Loss of function mutations in the DNA methyltransferase DNMT3A are highly recurrent in acute myeloid leukemia (AML). DNMT3A and DNMT3B encode the two methyltransferases that are primarily responsible for the de novo methylation of specific DNA sequences during cellular differentiation. DNMT3A mutations are rarely found in AML patients with translocations that create oncogenic fusion genes (e.g. PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, and MLL-X). To begin to define the reasons why these mutations do not occur together, we used retroviral vectors to express PML-RARA, RUNX1-RUNX1T1, and MLL-AF9 in the bone marrow cells of wild type (WT) or Dnmt3a deficient mice; we also examined the hematopoietic phenotypes of Ctsg-PML-RARA animals (which express PML-RARA in early hematopoietic progenitors and myeloid precursors) with and without Dnmt3a. We demonstrated that the methyltransferase activity of Dnmt3a (but not Dnmt3b) is required for aberrant self-renewal ex vivo that is driven by PML-RARA (but not RUNX1-RUNX1T1 or MLL-AF9); furthermore, the PML-RARA-driven competitive transplantation advantage and leukemia generation both required Dnmt3a. Together, these findings demonstrate that PML-RARA is specifically dependent on Dnmt3a to initiate APL in mice, and may explain why loss-of-function DNMT3A mutations are not found in patients with acute promyelocytic leukemia.
2015-10-01 | GSE68844 | GEO