TRIM28 is essential for erythroblast differentiation in the mouse
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE49843 | GEO | 2013/10/04
SECONDARY ACCESSION(S): PRJNA215083
REPOSITORIES: GEO
Similar Datasets
Project description:We discovered that Trim28 genetic loss in the adult mouse leads to defective immature erythropoiesis in the bone marrow and consequently to anemia.We further found that TRIM28 controls erythropoiesis in a cell-autonomous manner by inducibly deleting Trim28 exclusively in hematopoietic cells. Finally, in the absence of TRIM28 we observed increased apoptosis as well as diminished expression of multiple erythroid transcription factors and heme biosynthetic enzymes in immature erythroid cells. Thus, TRIM28 is essential for the cell-autonomous development of immature erythroblasts in the bone marrow. To induce Cre recombinase from the Mx1Cre transgene, poly(I:C) was injected 5 times every other day. Mice were analyzed two weeks after completion of poly(I:C) administration. TRIM28 mutant mice generate two distinct types of immature erythroid cells; KOa, with 5-8% of the Trim28 gene remaining undeleted (still bearing 26% of residual mRNA), and KOb, with 1-4% of the gene remaining undeleted (and with 18% of mRNA remaining).
2013-10-04 | E-GEOD-49843 | biostudies-arrayexpress
Project description:Human studies of Plasmodium vivax in the bone marrow are scarce. Here, we present a detailed characterization of bone marrow aspirates taken from a P. vivax patient with high parasitaemia on admission and 42 days after treatment. Analysis of miRNAs related to erythropoiesis revealed a distinct series of differentially expressed miRNAs during infection compared to at convalescence. These results suggest that parasites in the bone marrow affect erythropoiesis.
2017-02-25 | GSE78516 | GEO
Project description:Diamond-Blackfan anemia (DBA) is characterized by anemia and cancer susceptibility, and is caused by mutations in ribosomal genes, including Rpl11. Here, we report that Rpl11-heterozygous embryos are not viable, and homozygous deletion of Rpl11 in adult mice results in death within a few weeks, accompanied by bone marrow aplasia and intestinal atrophy. Importantly, deletion of a single Rpl11 allele in adult mice results in anemia associated to decreased erythroid progenitors and defective erythroid maturation. These phenotypes are also present in mice transplanted with inducible heterozygous Rpl11 bone marrow, indicating a cell-autonomous role of RPL11 in erythropoiesis. Additionally, fibroblasts lacking one or both Rpl11 alleles show defective p53 activation upon ribosomal stress or DNA damage. Furthermore, fibroblasts and hematopoietic tissues from heterozygous Rpl11 mice present higher basal cMYC levels. Accordingly, heterozygous Rpl11 mice are highly susceptible to radiation-induced lymphomagenesis. We conclude that Rpl11-deficient mice recapitulate DBA disorder, including cancer predisposition. RNAseq profiles of bone marrow hematopoietic progenitors cells from WT (Rpl11+/+:: Tg.UbC-CreERT2) and LOX (Rpl11+/lox::Tb.Ub-CreERT2) mice, n=4 independent animals per genotype
2015-09-01 | E-GEOD-72537 | biostudies-arrayexpress
Project description:Ter-119 is a better murine erythroid selection marker than CD71 for bulk immunomics, murine bone marrow and fetal liver erythroid cells have different antimicrobial immune transcriptome signatures, murine bone marrow erythropoiesis is comprised of two branches In this study, we decided to benchmark erythroid cells’ selection and enrichment markers – CD71 and Ter-119 via bulk immune transcriptomics by Nanostring and perform bulk immune transcriptome profiling of Ter-119+ erythroid cells from the bone marrow and the fetal liver by Nanostring.
2023-07-31 | GSE238190 | GEO
Project description:Erythropoiesis takes place mostly in bone marrow and ends in blood. Previous studies have shown that hypoxia has direct effects on the bone marrow, which could promotes erythropoiesis by modulating erythroid progenitor maturation. However, how bone marrow microenvironment participates in erythropoiesis under hypoxia still need further clarification. In this study, we analyzed transcriptional changes of bone marrow cells of mice exposed to 5000 m altitude hypoxia for 1 week. We profiled the top 20 up-regulated secreted factor genes after treatment with hypoxia, and found TFPI was one of the secreted factor genes with the highest expression.
2024-03-01 | GSE224993 | GEO
Project description:The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma. A multiple myeloma patient developed pure red cell aplasia (PRCA) following RVd treatment, despite the absence of common PRCA triggers. In vitro analyses revealed lenalidomide as a pivotal disruptor of erythropoiesis. Single-cell transcriptome analysis unveiled hyperactive CD8+ T cells and impaired erythropoiesis in the patient's bone marrow. Unexpectedly, the patient's erythroid cells displayed abnormally high expression of genes in the antigen presentation pathway, particularly those for major histocompatibility class I (MHC-I) molecules. Functional assays demonstrated that lenalidomide treatment further augmented MHC-I expression in the patient's erythroid cells. Blocking MHC-I or depleting T cells alleviate the defective erythropoiesis of PRCA, suggesting that the interaction between erythroid cells with elevated MHC-I and T cells in the bone marrow might contribute to PRCA. Taken together, our study revealed a novel mechanism underlying lenalidomide-induced PRCA in treating cancer patients.
2024-09-03 | PXD055495 |
Project description:Understanding the pattern of gene expression and identifying the specific genes expressed during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here we have isolated four distinct populations of erythroblasts at successive erythropoietin-dependent stages of erythropoiesis including the terminal, pyknotic stage. The transcriptome has been determined using Affymetrix arrays. First, we show that cells sorted by surface expression profile express not only significantly fewer genes than unsorted cells, but also significantly more differences in the expression levels of particular genes between stages than unsorted cells, demonstrating the importance of working with defined cell populations to identify lineage and temporally-specific patterns of gene expression. Second, using standard software and matched filtering we identify eleven differentially regulated genes and one continuously expressed gene previously undetected in erythroid expression studies with unknown roles in erythropoiesis (CA3, CALB1, CTSL2, FKBP1B, GSDMB, ITLN1, LIN7B, RRAD, RUNDC3A, UNQ1887, ZNF805, MYL12B). Finally, using transcription factor binding site analysis we identify potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts are a resource for functional studies of erythropoietic protein function and gene regulation.
2011-03-02 | GSE22552 | GEO
Project description:Understanding the pattern of gene expression and identifying the specific genes expressed during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here we have isolated four distinct populations of erythroblasts at successive erythropoietin-dependent stages of erythropoiesis including the terminal, pyknotic stage. The transcriptome has been determined using Affymetrix arrays. First, we show that cells sorted by surface expression profile express not only significantly fewer genes than unsorted cells, but also significantly more differences in the expression levels of particular genes between stages than unsorted cells, demonstrating the importance of working with defined cell populations to identify lineage and temporally-specific patterns of gene expression. Second, using standard software and matched filtering we identify eleven differentially regulated genes and one continuously expressed gene previously undetected in erythroid expression studies with unknown roles in erythropoiesis (CA3, CALB1, CTSL2, FKBP1B, GSDMB, ITLN1, LIN7B, RRAD, RUNDC3A, UNQ1887, ZNF805, MYL12B). Finally, using transcription factor binding site analysis we identify potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts are a resource for functional studies of erythropoietic protein function and gene regulation. PBMC-derived erythroblasts grown in vitro were harvested at the CFU-E, Pro-E, Int-E and Late-E stages and FACS sorted based on expression of cell surface markers. RNA was extracted from those populations which met rigorous specifications of time cultured in the presence of erythropoietin, morphology and CD36, CD71 and CD235a expression. For each stage, 3 chips were hybridised, each representing a pool of 4 different samples. In addition to these 12 chips, one chip representing a pool of RNA extracted from unsorted cells at each stages was also hybridised.
2011-03-02 | E-GEOD-22552 | biostudies-arrayexpress
Project description:JAK2V617F mutation is found in most patients with a myeloproliferative neoplasm (MPN), including polycythemia vera (PV), essential thrombocythemia (ET). We have demonstrated that heterozygous human JAK2V617F are associated with ET-like phenotypes while homozygosity for human JAK2V617F results in a striking phenotypic switch from an ET-like to PV-like phenotype. The resultant erythrocytosis is driven by increased numbers of erythroid progenitors and enhanced erythroblast proliferation. To establish the molecular mechanisms and pathways involved in the erythrocytosis, microarray was performed on bone marrow erythroblasts isolated from 8-10 weeks old homozygous, heterozygous mice and wildtype controls (3 mice for each genotype).
2014-03-26 | E-MTAB-2427 | biostudies-arrayexpress
Project description:Diamond-Blackfan anemia (DBA) is characterized by anemia and cancer susceptibility, and is caused by mutations in ribosomal genes, including Rpl11. Here, we report that Rpl11-heterozygous embryos are not viable, and homozygous deletion of Rpl11 in adult mice results in death within a few weeks, accompanied by bone marrow aplasia and intestinal atrophy. Importantly, deletion of a single Rpl11 allele in adult mice results in anemia associated to decreased erythroid progenitors and defective erythroid maturation. These phenotypes are also present in mice transplanted with inducible heterozygous Rpl11 bone marrow, indicating a cell-autonomous role of RPL11 in erythropoiesis. Additionally, fibroblasts lacking one or both Rpl11 alleles show defective p53 activation upon ribosomal stress or DNA damage. Furthermore, fibroblasts and hematopoietic tissues from heterozygous Rpl11 mice present higher basal cMYC levels. Accordingly, heterozygous Rpl11 mice are highly susceptible to radiation-induced lymphomagenesis. We conclude that Rpl11-deficient mice recapitulate DBA disorder, including cancer predisposition.
2015-09-01 | GSE72537 | GEO