Analysis of RNA expression under AhR antagonist treatment in human HSPCs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE184779 | GEO | 2022/06/01
REPOSITORIES: GEO
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Project description:We demonstrated to examine the effect of AhR antagonists on the specific lineage-biased differentiation of HSPC. To confirm this, CD34+ cells isolated from cord blood were cultured with two antagonists (CH223191 and StemRegenin 1) for 14 days to monitor their phenotype, and chromatin immunoprecipitation DNA was extracted from cultured cells on the 14th day of culture. We sought to explain the relationship between the action of AhR-antagonist complex and the megakaryocyte lineage-biased differentiation of HSPC with these ChIP-seq results.
2022-06-01 | GSE184778 | GEO
Project description:Hematopoietic stem/progenitor cell transplantation (HSCT) is a well-established treatment option for hematological and other disorders. Umbilical cord blood (UCB) is a rich source of hematopoietic stem and progenitor cells (HSPCs). Cluster of Differentiation (CD)34 is commonly used as a cell surface marker to identify and isolate HSPCs. Transplantation using a single UCB unit may be associated with delayed hematopoietic reconstitution as it may not contain a sufficient number of HSPCs required for adult transplantation. One way of overcoming this limitation is through ex vivo expansion of UCB-derived HSPCs using the aryl hydrocarbon receptor (AhR) antagonist, StemRegenin-1 (SR1), which promotes the expansion of HSPCs. Our study investigated the effects of SR1 on the transcriptome of expanded CD34+ cells from UCB, and we also report on a comparison between the transcriptome profiles of 7-day expanded and non-expanded CD34+ cells. CD34+ HSPCs expanded with SR1 for 7 days displayed two significantly downregulated genes, cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) and erythrocyte membrane protein band 4.1-like 3 (EPB41L3), when compared to controls (without SR1). Transcriptome analysis of CD34+ HSPCs expanded for 7 days using SR1 revealed that 391 genes were significantly upregulated, while 456 genes were significantly downregulated when compared to non-expanded CD34+ cells. In conclusion, though hundreds of genes were differentially expressed between SR1-expanded and non-expanded CD34+ HSPCs, only two genes were significantly downregulated in cells expanded for 7 days with SR1 versus control at the same time point (without SR1).
2024-09-25 | GSE146810 | GEO
Project description:Human CD34+ progenitors can be in vitro differentiated into proplatelet-producing megakaryocytes (MKs) within 17 days. During this course, 4 cell populations emerge, phenotypically defined as CD34+CD41+ at day 7 (D7) and CD34+CD41+CD9- at D10 and D14 —qualified as “productive” because they can differentiate into proplatelet-forming cells during the D14-D17 period— and CD34-CD41+ or CD34+CD41+CD9+ at day 10 —qualified as “unproductive”, because unable to form proplatelets later. The productive pathway is boosted by the addition of SR1 at D0 and D7. To clarify the features of the productive and unproductive pathways, as well as the effect of SR1, the transcriptomes of the cell populations present at D0, 7, 10 and 14, generated in the presence of the absence of SR1 were determined by RNA-Seq.
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Project description:The goal of the study was to identify genes that are directly or indirectly coregulated by the AhR pathway in primary human AML cells. Patient AML cells were treated for 16 hours with the two indirubin derivatives 6-bromoindirubin-3'oxime (BIO), 1-Methyl-6-bromoindirubin-3'oxime (MeBIO), the AHR-antagonist SR1 (StemReginin1), combinations of BIO+SR1 and MeBIO+SR1 or DMSO alone at indicated concentrations prior to RNA extraction for sequencing. RNA-Seq performed on 5 primary AML samples fresh (t0) and after exposure to AhR-agonists (2), -antagonist (1), and DMSO Contributor: Leucegene Project, IRIC
2016-07-20 | E-GEOD-48843 | biostudies-arrayexpress
Project description:SJL pregnant mice were infected with Zika virus and treated with nanoliposomes loaded with AHR antagonist CH223191 or control nanoliposomes. RNA-Seq analysis was performed in CNS samples from the pups.
2020-04-13 | GSE147094 | GEO
Project description:Targeting the estrogen signaling pathway has proved to be of great value in the treatment of human breast cancer. Tamoxifen, a selective estrogen receptor modulator (SERM), is the most widely used antiestrogen. However, only 40-50% of patients with estrogen receptor (ER) positive breast cancer benefit from tamoxifen treatment and 30-50% acquire resistance and the disease progresses. Continuous treatment with conventional therapy may contribute to cancer progression in recurring cancers through the accumulation of drug resistant cancer progenitors. We found that MCF7 tamoxifen-resistant (TAM-R) cells possess a significantly higher proportion of cancer progenitor cells than tamoxifen-sensitive MCF7 cells. Our results indicate that the chemokine receptor CXCR4 plays an important role in the maintenance of cancer progenitors in a tamoxifen-resistant cell line and downregulation of CXCR4 signaling by small molecule antagonists specifically inhibits growth of a stem-like cell population in tamoxifen-resistant tumors both in vitro and in vivo. Whole genome gene expression analysis revealed aryl hydrocarbon receptor (AhR) signaling as one of the top networks that is differentially regulated in MCF7(TAM-R) xenograft tumors treated with the CXCR4 antagonist AMD3100 as compared to MCF7 tumors. Further, small molecule antagonists of AhR signaling specifically inhibit the progenitor population in MCF7(TAM-R) cells suggesting that the aryl hydrocarbon receptor could be a putative target for the treatment of tamoxifen-resistant breast cancers. Introduction transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy. Tamoxifen resistant or sensitive xenografts; mice treated with estrogen and/or CXCR4 modulators
2012-12-21 | E-GEOD-31831 | biostudies-arrayexpress
Project description:The goal of the study was to identify genes that are directly or indirectly coregulated by the AhR pathway in primary human AML cells. Patient AML cells were treated for 16 hours with the two indirubin derivatives 6-bromoindirubin-3'oxime (BIO), 1-Methyl-6-bromoindirubin-3'oxime (MeBIO), the AHR-antagonist SR1 (StemReginin1), combinations of BIO+SR1 and MeBIO+SR1 or DMSO alone at indicated concentrations prior to RNA extraction for sequencing.
2016-07-20 | GSE48843 | GEO
Project description:Although practiced clinically for more than 40 years, the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy. LGC006, a less potent SR1 analog, was also examined. KEYWORDS: two compounds, multiple doses, one time point two compounds, multiple doses, one time point
2011-04-04 | E-GEOD-28359 | biostudies-arrayexpress
Project description:Targeting the estrogen signaling pathway has proved to be of great value in the treatment of human breast cancer. Tamoxifen, a selective estrogen receptor modulator (SERM), is the most widely used antiestrogen. However, only 40-50% of patients with estrogen receptor (ER) positive breast cancer benefit from tamoxifen treatment and 30-50% acquire resistance and the disease progresses. Continuous treatment with conventional therapy may contribute to cancer progression in recurring cancers through the accumulation of drug resistant cancer progenitors. We found that MCF7 tamoxifen-resistant (TAM-R) cells possess a significantly higher proportion of cancer progenitor cells than tamoxifen-sensitive MCF7 cells. Our results indicate that the chemokine receptor CXCR4 plays an important role in the maintenance of cancer progenitors in a tamoxifen-resistant cell line and downregulation of CXCR4 signaling by small molecule antagonists specifically inhibits growth of a stem-like cell population in tamoxifen-resistant tumors both in vitro and in vivo. Whole genome gene expression analysis revealed aryl hydrocarbon receptor (AhR) signaling as one of the top networks that is differentially regulated in MCF7(TAM-R) xenograft tumors treated with the CXCR4 antagonist AMD3100 as compared to MCF7 tumors. Further, small molecule antagonists of AhR signaling specifically inhibit the progenitor population in MCF7(TAM-R) cells suggesting that the aryl hydrocarbon receptor could be a putative target for the treatment of tamoxifen-resistant breast cancers. Introduction transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy.
2012-12-21 | GSE31831 | GEO