Gene expression data of human chord blood hematopoietic progenior cells subjected to myeloid differentiation and transduced with lncRNA HOXA10-AS
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE123694 | GEO | 2020/01/01
REPOSITORIES: GEO
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Project description:The homeobox (Hox) transcription factor HOXA10 has been implicated in regulation of hematopoietic cell fate. Here, using a transgenic mouse model where expression of HOXA10 is tightly regulated in a graded, doxycyclin-dependent manner we demonstrate that several key commitment steps in hematopoietic differentiation have distinctly different outcomes depending on the expression level of HOXA10. Similarly, HOXA10 regulates hematopoietic stem cell (HSC) proliferation in a dose dependent manner, since intermediate levels of HOXA10 generated a 4.5-fold increase in long-term repopulating capacity after 13 days of liquid culture, whereas high levels reduced proliferation of HSCs. Interestingly, the effects on HSC proliferation were associated with altered expression of several known regulators of stem cell self-renewal. Taken together, our findings reveal entirely novel functional and molecular aspects of HOXA10 in regulation of hematopoiesis and emphasize the need for tightly regulated production of HOX proteins in possible future applications of stem cell expansion. Keywords: Affymetrix
2006-03-20 | GSE3861 | GEO
Project description:The homeobox gene HOXA10 plays a key role in endometrial differentiation during embryogenesis and is abundantly expressed in the adult endometrium and decidual cells. In the adult endometrium the expression of HOXA10 is regulated by estrogen and progesterone and the levels are highest in the decidualized cells. We have shown that HOXA10 is required in the endometrial cells to maintain the decidual cell phenotype. In this study we aimed to determine the molecular mechanisms by which HOXA10 maintains the decidual phenotype and the other roles it might have in decidual physiology. In vitro decidualized human endometrial stromal cells were knocked down for HOXA10 using siRNA and gene expression profiles of the scrambled and HOXA10 siRNA transfected cells were compared at 24, 48 and 72 h post transfection. Several genes having multiple functions were found to be differentially expressed. We postulate that HOXA10 is required by the decidual cells to support immune cell differentiation, trophoblast invasion and cellular remodeling.
2012-02-14 | GSE35801 | GEO
Project description:The Rosa-rtTAnls/tetO-HoxA10 mouse model is a Tetracycline-On (tetO) system in which the expression level of HoxA10 can be tightly regulated and overexpressed under administration of the Doxycycline (DOXY) in the drinking bottle of mice or fed with Ciproxine (CIPRO) as a negative control of HoxA10 expression. <br>In this experiment, we analyzed expressed genes derived from microarray analysis of HoxA10 Acute Myeloid Leukemia (AML) cells induced in primary recipient mice (1ary) and in secondary recipient mice, with HoxA10 overexpression (DOXY) or after turning off the HoxA10 overexpression (CIPRO).<br>Concerning the biological design, we compared leukemia induced in primary recipient mice (1ary) to normal bone marrow (normal BM). We compared also primary leukemia (1ary) to leukemia induced in secondary recipient mice (2ary) induce by continuous expression of HoxA10 (DOXY) to leukemia induced in secondary recipient mice after turning off expression of HoxA10 (CIPRO) and analyse relapse growth of leukemic cells after turning off HoxA10.<br>Concerning the protocol, the leukemic cells originated from two independent primary AML donor mice (cl1, cl2, cl3, cl4) are injected in secondary recipient mice, which are monitored for reoccurrence of leukemia. AML are induced by Doxycycline (Doxy) or Ciproxine as negative control (Cipro), by administration of 0.2g/mL continuously in the drinking bottle until development of AML. In sick mice, femurs and tibias were removed and cleaned of soft tissue, bones were crushed, and the cell suspension was filtered over a 100-m pore size cell strainer filter (Falcon; Becton Dickinson). Total RNA from BM cells of ciproxine and doxycycline receiving recipient mice suffering from leukemia was extracted from bone marrow cells (Qiagen). RNA concentration and integrity were respectively determined by NanoDrop spectrophotometry (NanoDrop technologies) and a Bioanalyser (Agilent technology). Reverse transcription using Illumina TotalPrep RNA Amplification Kit (Ambion) and hybridization to Mouse WG-6 Expression v1.1 BeadChips (Illumina) interrogating more than 45,000 transcripts were performed by the Swegene Center for Integrative Biology at Lund University (SCIBLU).
2010-09-13 | E-MEXP-2491 | biostudies-arrayexpress
Project description:Muscle stem cells (satellite cells) are distributed throughout the body and have heterogeneous properties among muscles. However, functional topographical genes in satellite cells of adult muscle remain unidentified. Here, we show that expression of Homeobox-A (Hox-A) cluster genes accompanied with DNA hypermethylation of the Hox-A locus was robustly maintained in both somite-derived muscles and their associated satellite cells in adult mice, which recapitulates their embryonic origin. Somite-derived satellite cells were clearly separated from cells derived from cranial mesoderm in Hoxa10 expression. Hoxa10 inactivation led to genomic instability and mitotic catastrophe in somite-derived satellite cells in mice and human. Satellite cell–specific Hoxa10 ablation in mice resulted in a decline in the regenerative ability of somite-derived muscles, which were unobserved in cranial mesoderm–derived muscles. Thus, our results show that Hox gene expression profiles instill the embryonic history in satellite cells as positional memory, potentially modulating region-specific pathophysiology in adult muscles.
2021-04-17 | GSE139315 | GEO
Project description:The Rosa-rtTAnls/tetO-HoxA10 mouse model is a Tetracycline-On (tetO) system in which the expression level of HoxA10 can be tightly regulated and overexpressed under administration of the Doxycycline (Doxy) in the drinking bottle of mice or fed with Ciproxine (Cipro) as a negative control of HoxA10 expression. <br>In this experiment, we analyzed expressed transcripts derived from microarray analysis of HoxA10 Acute Myeloid Leukemia (AML) cells induced in secondary recipient mice, with HoxA10 overexpression (Doxy) or after turning off the HoxA10 overexpression (Cipro).<br><br>Concerning the biological design, we compared leukemia in secondary recipient mice induced by continuous expression of HoxA10 (Doxy) to leukemia induced after turning off expression of HoxA10 (Cipro) and analyse relapse growth of leukemic cells after turning off HoxA10.<br><br>Concerning the protocol, the leukemic cells originated from two independent primary AML donor mice (cl1 and cl2) are injected in secondary recipient mice, which are monitored for reoccurrence of leukemia. AML are induced by Doxycycline (Doxy) or Ciproxine as negative control (Cipro), by administration of 0.2g/mL continuously in the drinking bottle until development of AML. In sick mice, femurs and tibias were removed and cleaned of soft tissue, bones were crushed, and the cell suspension was filtered over a 100-m pore size cell strainer filter (Falcon; Becton Dickinson). Total DNA from BM cells of Cipro and Doxy receiving recipient mice suffering from leukemia was extracted from bone marrow cells (Qiagen). DNA concentration and integrity were respectively determined by NanoDrop spectrophotometry (NanoDrop technologies) and a Bioanalyser (Agilent technology). Hybridization to Mouse CGH microarray 244A (Agilent) were performed by the Atlas Biolabs (Germany). Reverse transcription using Illumina TotalPrep RNA Amplification Kit (Ambion) and hybridization to Mouse WG-6 Expression v1.1 BeadChips (Illumina) were performed by the Swegene Center for Integrative Biology at Lund University (SCIBLU).
2010-08-18 | E-MEXP-2876 | biostudies-arrayexpress
Project description:The Rosa-rtTAnls/tetO-HoxA10 mouse model is a Tetracycline-On (tetO) system in which the expression level of HoxA10 can be tightly regulated and overexpressed under administration of the Doxycycline (Doxy) in the drinking bottle of mice or fed with Ciproxine (Cipro) as a negative control of HoxA10 expression. <br>In this experiment, we analyzed expressed transcripts derived from microarray analysis of HoxA10 Acute Myeloid Leukemia (AML) cells induced in secondary recipient mice, with HoxA10 overexpression (Doxy) or after turning off the HoxA10 overexpression (Cipro).<br><br>Concerning the biological design, we compared leukemia in secondary recipient mice induced by continuous expression of HoxA10 (Doxy) to leukemia induced after turning off expression of HoxA10 (Cipro) and analyse relapse growth of leukemic cells after turning off HoxA10.<br><br>Concerning the protocol, the leukemic cells originated from two independent primary AML donor mice (cl3 and cl4) are injected in secondary recipient mice, which are monitored for reoccurrence of leukemia. AML are induced by Doxycycline (Doxy) or Ciproxine as negative control (Cipro), by administration of 0.2g/mL continuously in the drinking bottle until development of AML. In sick mice, femurs and tibias were removed and cleaned of soft tissue, bones were crushed, and the cell suspension was filtered over a 100-m pore size cell strainer filter (Falcon; Becton Dickinson). Total DNA from BM cells of Cipro and Doxy receiving recipient mice suffering from leukemia was extracted from bone marrow cells (Qiagen). DNA concentration and integrity were respectively determined by NanoDrop spectrophotometry (NanoDrop technologies) and a Bioanalyser (Agilent technology). Hybridization to Mouse CGH microarray 244A (Agilent) were performed by the Atlas Biolabs (Germany). Reverse transcription using Illumina TotalPrep RNA Amplification Kit (Ambion) and hybridization to Mouse WG-6 Expression v2 BeadChips (Illumina) were performed by the Swegene Center for Integrative Biology at Lund University (SCIBLU).
2010-08-21 | E-MEXP-2877 | biostudies-arrayexpress
Project description:The Rosa-rtTAnls/tetO-HoxA10 mouse model is a Tetracycline-On (tetO) system in which the expression level of HoxA10 can be tightly regulated and overexpressed under administration of the Doxycycline (Doxy) in the drinking bottle of mice or fed with Ciproxine (Cipro) as a negative control of HoxA10 expression.<br><br>In this experiment, we analyzed molecular karyotype derived from CGH arrays analysis of HoxA10 Acute Myeloid Leukemia (AML) cells induced in primary recipient mice (1ary) and in secondary recipient mice, with HoxA10 overexpression (DOXY) or after turning off the HoxA10 overexpression (CIPRO). <br><br>Concerning the biological design, we compared leukemia induced in primary recipient mice (1ary) to normal bone marrow (normal control). We compared also primary leukemia (1ary) to leukemia induced in secondary recipient mice induce by continuous expression of HoxA10 (Doxy). Finally we compared leukemia induced in secondary recipient mice induce by continuous expression of HoxA10 (Doxy) to leukemia induced in secondary recipient mice after turning off expression of HoxA10 (Cipro) to analyse relapse growth of leukemic cells after turning off HoxA10.<br><br>Concerning the protocol, the leukemic cells originated from two independent primary AML donor mice (cl1 and cl2) are injected in secondary recipient mice, which are monitored for reoccurrence of leukemia. AML are induced by Doxycycline (Doxy) or Ciproxine as negative control (Cipro), by administration of 0.2g/mL continuously in the drinking bottle until development of AML. In sick mice, femurs and tibias were removed and cleaned of soft tissue, bones were crushed, and the cell suspension was filtered over a 100-m pore size cell strainer filter (Falcon; Becton Dickinson). Total DNA from BM cells of Cipro and Doxy receiving recipient mice suffering from leukemia was extracted from bone marrow cells (Qiagen). DNA concentration and integrity were respectively determined by NanoDrop spectrophotometry (NanoDrop technologies) and a Bioanalyser (Agilent technology). Hybridization to Mouse CGH microarray 244A (Agilent) were performed by the Atlas Biolabs (Germany).<br>
2009-12-05 | E-MEXP-2473 | biostudies-arrayexpress
Project description:We used a machine-learning framework to systematically discover prognostic long non-coding RNAs (lncRNAs) in 9,446 patient tumors of 30 types. We identified 166 prognostic lncRNAs whose transcript abundance correlated with patient risk and improved the performance of common clinical variables and molecular tumor subtypes. In lower-grade gliomas, discrete activation of HOXA10-AS indicated poor patient prognosis, neurodevelopmental pathway activation and a transcriptomic similarity to glioblastomas. To understand the role of HOXA10-AS in the hallmark pathways of glioma, we used RNA-seq to profile the patient-derived G797 glioma cells with siRNA-mediated HOXA10-AS knockdown (KD) and pcDNA3.1-Neomycin-mediated overexpression (OE) phenotypes. Both KD and OE were validated using RT-PCR. We found a pronounced transcriptional response to HOXA10-AS deregulation with 1,715 and 408 differentially expressed protein-coding genes detected in KD and OE cells, respectively (FDR < 0.05, absolute FC > 1.2), including 23 genes detected in both experiments, as well as known genes involved in glioma biology and Hippo signaling. Our study underscores the pan-cancer potential of the non-coding transcriptome for developing molecular biomarkers and innovative therapeutic strategies.
2021-10-02 | E-MTAB-10944 | biostudies-arrayexpress
Project description:The homeobox gene HOXA10 plays a key role in endometrial differentiation during embryogenesis and is abundantly expressed in the adult endometrium and decidual cells. In the adult endometrium the expression of HOXA10 is regulated by estrogen and progesterone and the levels are highest in the decidualized cells. We have shown that HOXA10 is required in the endometrial cells to maintain the decidual cell phenotype. In this study we aimed to determine the molecular mechanisms by which HOXA10 maintains the decidual phenotype and the other roles it might have in decidual physiology. In vitro decidualized human endometrial stromal cells were knocked down for HOXA10 using siRNA and gene expression profiles of the scrambled and HOXA10 siRNA transfected cells were compared at 24, 48 and 72 h post transfection. Several genes having multiple functions were found to be differentially expressed. We postulate that HOXA10 is required by the decidual cells to support immune cell differentiation, trophoblast invasion and cellular remodeling. In vitro decidualized priamry cultures of human endometrial strmal cells transfected with a siRNA againts HOXA10 or a scrambled siRNA. Cells harvested at 24, 48 and 72 h post transfection. Dual channel hybridization with dye swap design in biological replicates
2012-02-14 | E-GEOD-35801 | biostudies-arrayexpress
Project description:Circular RNAs (circRNAs) constitute an abundant class of covalently closed non-coding RNA molecules that are formed by backsplicing from eukaryotic protein-coding genes. Recent studies have shown that circRNAs can act as microRNA or protein decoys as well as transcriptional regulators. However, the functions of most circRNAs are still poorly understood. Because circRNA sequences overlap with their linear parent transcripts, depleting specific circRNAs without affecting host gene expression remains a challenge. Here, we assessed the utility of LNA-modified antisense oligonucleotides (ASOs) to knock down circRNAs for loss-of-function studies. We identified 5807 circRNAs in total RNA sequencing data from 4 liver cancer cell lines and used the back splice junction (BSJ) sequences of 7 validated circRNAs as target sites for designing different LNA-modified ASOs for circRNA knockdown. We found that while most RNase H-dependent gapmer ASOs mediate effective knockdown of their target circRNAs, some gapmers reduce the levels of the linear parent transcript and may also cause degradation of unintended off-targets. The circRNA targeting specificity can be enhanced using design-optimized gapmer ASOs or LNA/DNA mixmer ASOs, which display potent and specific circRNA knockdown with a minimal effect on the host genes or predicted off-targets. In summary, our results demonstrate that LNA-modified ASOs complementary to BSJ sequences mediate robust knockdown of circRNAs in vitro and, thus, represent a useful tool to explore the biological roles of circRNAs in loss-of-function studies in cultured cells and animal models.
2022-11-01 | GSE145592 | GEO