The dose-dependent role of PU.1 in Myeloid differentiation
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ABSTRACT:
PROVIDER: PRJNA315126 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A doxycycline-inducible system was used to induce PU.1 expression in cultured myeloid cell lines. The parent cell line used was BN (Kamath et al., Leukemia 22:1214-1225, 2008).
2017-02-14 | GSE79191 | GEO
Project description:A doxycycline-inducible system was used to induce PU.1 expression in cultured myeloid cell lines. The parent cell line used was BN (Kamath et al., Leukemia 22:1214-1225, 2008). Induction of PU.1 expression was previously demonstrated to lead to cell cycle exit and decreased expression of cell cycle genes. The goal of this study is expression profiling of small RNAs in cells with reduced or elevated PU.1 expression.
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2017-02-14 | GSE79193 | GEO
Project description:Mirc11 role in myeloid differentiation
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Project description:We have shown that β-catenin overexpression induced blockage of monocyte-macrophage differentiation by inhibiting PU.1-targeted gene transcription including Egr2 expression in myeloid progenitor cells. Our results suggest that compromised PU.1-targeted gene transcription induced by β-catenin overexpression, at least partially, may mediate a pathogenic role of β-catenin in myeloid leukemia. PUER cells were infected with retrovirus expressing beta-catenin-S33Y or control vector MIGR1. Five days after infection, the GFP positive cells were sorted by flow cytometry, and were treated with 4-OHT to induce the expression of PU.1. Total RNA was exacted from cell samples and purified by RNeasy Micro kit (Qiagen). cRNAs were generated and hybridized to the mouse whole genome 4Ã44K arrays according to manufacturerâs instructions (Agilent Technologies).
2016-04-06 | E-GEOD-79932 | biostudies-arrayexpress
Project description:The transcription factor PU.1 occupies a central role in controlling myeloid and early B cell development and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis-element (URE) whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the URE alone is insufficient to confer physiological PU.1 expression, but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays and detailed molecular analyses we present evidence that Pu.1 is regulated by a novel mechanism involving cross-talk between different cis-elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell-type specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements. Two DNaseI hypersensitivity datasets; bone marrow derived-macrophages and Splenic CD19+IgM+ B cells were used to study PU.1 regulatory elements
2011-02-21 | E-GEOD-26550 | biostudies-arrayexpress
Project description:We have shown that β-catenin overexpression induced blockage of monocyte-macrophage differentiation by inhibiting PU.1-targeted gene transcription including Egr2 expression in myeloid progenitor cells. Our results suggest that compromised PU.1-targeted gene transcription induced by β-catenin overexpression, at least partially, may mediate a pathogenic role of β-catenin in myeloid leukemia.
2016-04-06 | GSE79932 | GEO
Project description:Hematopoietic stem cells sustain life-long blood production. While they are the known cellular origin of aging-associated myeloid malignancies, such as acute myeloid leukemia (AML), mechanisms driving their malignant transformation have remained elusive. Epigenetic dysregulation following acquired loss-of-function mutations of DNA methyl-cytosine dioxygenase Ten-Eleven Translocation-2 (TET2) occurs frequently in the elderly leading to cytosine hypermethylation in and around DNA binding sites of master transcription factors, including PU.1. Here we show that Tet2 deficient hematopoietic stem and progenitor cells (HSPC) undergo malignant transformation upon compromised PU.1 gene regulation. Leukemic stem and progenitor cells show hypermethylation at PU.1 binding sites and fail to activate PU.1-depenent myeloid enhancers, and are hallmarked by a defined signature of impaired genes shared with human AML. Our study demonstrates that Tet2 and PU.1 cooperate in suppressing leukemogenesis in HSPC and establishes a methylation sensitive PU.1-dependent gene network as a unifying feature in acute myeloid leukemia.
2022-07-31 | GSE191052 | GEO
Project description:Hematopoietic stem cells sustain life-long blood production. While they are the known cellular origin of aging-associated myeloid malignancies, such as acute myeloid leukemia (AML), mechanisms driving their malignant transformation have remained elusive. Epigenetic dysregulation following acquired loss-of-function mutations of DNA methyl-cytosine dioxygenase Ten-Eleven Translocation-2 (TET2) occurs frequently in the elderly leading to cytosine hypermethylation in and around DNA binding sites of master transcription factors, including PU.1. Here we show that Tet2 deficient hematopoietic stem and progenitor cells (HSPC) undergo malignant transformation upon compromised PU.1 gene regulation. Leukemic stem and progenitor cells show hypermethylation at PU.1 binding sites and fail to activate PU.1-depenent myeloid enhancers, and are hallmarked by a defined signature of impaired genes shared with human AML. Our study demonstrates that Tet2 and PU.1 cooperate in suppressing leukemogenesis in HSPC and establishes a methylation sensitive PU.1-dependent gene network as a unifying feature in acute myeloid leukemia.
2022-07-31 | GSE194170 | GEO
Project description:Hematopoietic stem cells sustain life-long blood production. While they are the known cellular origin of aging-associated myeloid malignancies, such as acute myeloid leukemia (AML), mechanisms driving their malignant transformation have remained elusive. Epigenetic dysregulation following acquired loss-of-function mutations of DNA methyl-cytosine dioxygenase Ten-Eleven Translocation-2 (TET2) occurs frequently in the elderly leading to cytosine hypermethylation in and around DNA binding sites of master transcription factors, including PU.1. Here we show that Tet2 deficient hematopoietic stem and progenitor cells (HSPC) undergo malignant transformation upon compromised PU.1 gene regulation. Leukemic stem and progenitor cells show hypermethylation at PU.1 binding sites and fail to activate PU.1-depenent myeloid enhancers, and are hallmarked by a defined signature of impaired genes shared with human AML. Our study demonstrates that Tet2 and PU.1 cooperate in suppressing leukemogenesis in HSPC and establishes a methylation sensitive PU.1-dependent gene network as a unifying feature in acute myeloid leukemia.
2022-07-31 | GSE186146 | GEO