ScRNAseq of Hoxa10+ and Hoxa10-Lineage cells in uninjured and injured tibia
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE342267 | GEO | 2026/08/05
REPOSITORIES: GEO
Similar Datasets
Project description:scRNAseq of Hoxa10+ and Hoxa10-Lineage cells in uninjured and injured tibia
| PRJNA1507237 | ENA
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: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:Skeletal muscle is contractile tissue distributed throughout the body with functionally heterogeneous properties that may relate to region-specific pathophysiology of muscle diseases. Recent studies revealed that muscle stem cells (satellite cells) are a functional heterogeneous population in different muscles, dependent not only on fiber-types but also on embryonic origin. Homeobox (Hox) genes are key regulators of the embryonic body plan. Here, we showed that Hox-A cluster genes are robustly maintained in adult muscles and their associated satellite cells of both mice and humans in a body region-specific manner, whose distribution almost recapitulates their embryonic origin. The region-specific expression of Hox genes was linked to DNA hypermethylation status of Hox-A locus. Importantly, Hox gene expression is a functional memory; Hoxa10 inactivation in satellite cells led to genomic instability and mitotic catastrophe, resulting in a decline in the regionally specific regenerative ability of muscles in mice, even though Hox paralogs are known to be often functionally redundant. Thus, our results demonstrate that the topographic Hox gene expression profile could be a geotagging molecular signature that reflects the anatomical location and embryonic history of resident muscle stem cells, potentially contributing to regionally specific regulations of adult skeletal muscles.
2021-04-16 | GSE154056 | 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 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. LSK cells were sorted from rtTA-HA10 and cultured for 72 hours in complete serum free medium in three different concentrations of doxycycline (0, 0.1 and 0.5 µg/ml doxycycline). RNA was extracted using RNeasy Mini kit, Qiagen, labeled and amplified according to AffymetrixTM Two Cycle Target Labeling Protocol. Hybridization and washing was performed according to AffymetrixTM GeneChip Expression protocol. Chips were scanned using an AffymetrixTM GeneChip Scanner 3000. The Affymetrix software GCOS was used to generate cell intensity data files (CEL) from two independent experiments. The CEL file data was then imported into the GeneSpring® software version 7.2 (Silicon Genetics, Redwood City, CA). The GC-RMA method was used for normalization and data was processed as follows: values below 0.01 were set to 0.01. All of the genes in each sample were divided by the median of the specified list of 100 positive control genes present on the MOE430 v2 chip. All samples were then normalized against the median of the untreated control samples. Each measurement for each gene in the treated samples was divided by the median of that gene's measurements in the corresponding control samples. We judged genes to be differentially expressed when the difference in expression between two conditions was at least 2-fold.
2007-12-07 | E-GEOD-3861 | 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:Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of gene expression and cell fate decisions. We predicted HOXA10-AS as a novel non-coding regulator of hematopoiesis and leukemogenesis We overexpressed HOXA10-AS using a bidirectional vector construct, which resulted in impaired monocytic in vitro differentiation and myeloid colony-formation. In addition, shRNA, sgRNA and LNA-GapmeR mediated downregulation of HOXA10-AS resulted in reduced leukemic growth of KMT2A-r cell lines and patient blasts. (p≤0.05). Here we assess early effects of ectopic HOXA10-AS expression in human HSPC subjected to myeloid differentiation conditions.
2020-01-01 | GSE123694 | 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: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