Gene expression data of human chord blood hematopoietic progenior cells subjected to myeloid differentiation and transduced with lncRNA HOXA10-AS
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PROVIDER: PRJNA509607 | ENA |
REPOSITORIES: ENA
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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:Overexpression of HOXB4 in hematopoietic stem cells (HSCs) leads to increased self-renewal without causing hematopoietic malignancies in transplanted mice. The molecular basis of HOXB4-mediated benign HSC expansion in vivo is not well understood. To gain further insight into the molecular events underlying HOXB4-mediated HSC expansion, we analyzed gene expression changes at multiple time points in Lin-Sca1+c-kit+ (LSK) cells from mice transplanted with bone marrow (BM) cells transduced with a MSCV-HOXB4-ires-YFP vector. A distinct HOXB4 transcriptional program was reproducibly induced and stabilized by 12 weeks after transplant. Dynamic expression changes were observed in genes critical for HSC self-renewal as well as genes involved in myeloid and B cell differentiation. Prdm16, a transcription factor associated with human acute myeloid leukemia (AML), was markedly repressed by HOXB4 but upregulated by HOXA9 and HOXA10, suggesting that Prdm16 downregulation was involved in preventing leukemia in HOXB4 transplanted mice. Functional evidence to support this mechanism was obtained by enforcing co-expression of sPrdm16 and HOXB4, which led to enhanced self-renewal, myeloid expansion, and leukemia. Altogether, these studies define the transcriptional pathways involved in HOXB4 HSC expansion in vivo and identify repression of Prdm16 transcription as a mechanism by which expanding HSCs avoid leukemic transformation. 5-FU treated bone marrow cells from female C57Bl/6L mice were transduced with concentrated supernatant from GPE+86-derived producer cells containing MSCV-HOXB4-ires-YFP or MSCV-ires-GFP retroviral vectors. Transduced cells were transplanted into lethally irradiated C57Bl/6L mice. HOXB4-YFP or GFP expressing LSK cells were sorted from transplanted mice at 6, 12 and 24 weeks post transplantation, of which RNA was extracted for microarray.
2014-10-01 | E-GEOD-59804 | biostudies-arrayexpress
Project description:Overexpression of HOXB4 in hematopoietic stem cells (HSCs) leads to increased self-renewal without causing hematopoietic malignancies in transplanted mice. The molecular basis of HOXB4-mediated benign HSC expansion in vivo is not well understood. To gain further insight into the molecular events underlying HOXB4-mediated HSC expansion, we analyzed gene expression changes at multiple time points in Lin-Sca1+c-kit+ (LSK) cells from mice transplanted with bone marrow (BM) cells transduced with a MSCV-HOXB4-ires-YFP vector. A distinct HOXB4 transcriptional program was reproducibly induced and stabilized by 12 weeks after transplant. Dynamic expression changes were observed in genes critical for HSC self-renewal as well as genes involved in myeloid and B cell differentiation. Prdm16, a transcription factor associated with human acute myeloid leukemia (AML), was markedly repressed by HOXB4 but upregulated by HOXA9 and HOXA10, suggesting that Prdm16 downregulation was involved in preventing leukemia in HOXB4 transplanted mice. Functional evidence to support this mechanism was obtained by enforcing co-expression of sPrdm16 and HOXB4, which led to enhanced self-renewal, myeloid expansion, and leukemia. Altogether, these studies define the transcriptional pathways involved in HOXB4 HSC expansion in vivo and identify repression of Prdm16 transcription as a mechanism by which expanding HSCs avoid leukemic transformation.
2014-10-01 | GSE59804 | GEO
Project description:Long non-coding RNAs (lncRNAs) exert regulatory functions in a wide spectrum of biological contexts, and certain regulatory functions involve the formation of RNA-protein complexes. Discovering the structure/function of these complexes may unveil important functional insights. The DDX41 gene encoding the DEAD-box RNA helicase 41 protein (DDX41) is subject to extensive germline genetic variation, and certain variants create a predisposition to develop myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). While the importance of DDX41 for the control of hematopoiesis is established, many questions remain regarding the mechanisms of how DDX41 functions in hematopoietic stem and progenitor cells. Previously, we identified a DDX41-regulated lncRNA, growth arrest-specific 5 (Gas5) (Kim et al.). As Gas5 function in hematopoiesis is unknown, we analyzed protein interactors of Gas5 lncRNA using HyPR-MS (Hybridization Purification of RNA-Protein complexes followed by Mass Spectrometry). 28 proteins were identified as Gas5 lncRNA interactors, five of which were experimentally validated as Gas5 lncRNA interactors by RNA Immunoprecipitation qPCR (RIP-qPCR) analysis. The identification of protein interactors with a DDX41-regulated lncRNA establishes a foundation to guide future mechanistic and biological studies.c
2025-01-13 | PXD055956 | Pride
Project description:Long non-coding RNAs (lncRNAs) exert regulatory functions in a wide spectrum of biological contexts, and certain regulatory functions involve the formation of RNA-protein complexes. Discovering the structure/function of these complexes may unveil important functional insights. The DDX41 gene encoding the DEAD-box RNA helicase 41 protein (DDX41) is subject to extensive germline genetic variation, and certain variants create a predisposition to develop myelodysplastic syndrome and acute myeloid leukemia. While the importance of DDX41 for the control of hematopoiesis is established, many questions remain regarding the mechanisms of how DDX41 functions in hematopoietic stem and progenitor cells. Previously, we identified a DDX41-regulated lncRNA, growth arrest-specific 5 (Gas5). As Gas5 function in hematopoiesis is unknown, we analyzed protein interactors of Gas5 lncRNA using HyPR-MS (Hybridization Purification of RNA-Protein complexes followed by Mass Spectrometry). 303 proteins were identified as Gas5 lncRNA interactors, five of which were experimentally validated as Gas5 lncRNA interactors by RNA Immunoprecipitation qPCR (RIP-qPCR) analysis. The identification of protein interactors with a DDX41-regulated lncRNA establishes a foundation to guide future mechanistic and biological studies.
2025-07-17 | PXD062695 | Pride
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:Gene expression data of human chord blood hematopoietic progenitor cells subjected to myeloid differentiation and transduced with shRNAs against LINC00173
| PRJNA386330 | ENA
Project description:Knockdown of HCLS1 mRNA in CD34+ hematopoietic cells resulted in a severe diminished in vitro myeloid differentiation which was in line with downregulation of a set of genes, e.g., of Wnt or PI3K/Akt signaling cascades. We performed microarrays to evaluate specific genes and signaling systems regulated by HCLS1 in hematopoietic cells. CD34+ hematopoietic cells were isolated from the bone marrow of healthy individuals, transduced with lenitvirus-based RFP-expressed shRNA constructs targeting HCLS1 mRNA (two different shRNA constructs were used simultaneously) or scrambled control shRNA. After 4 days of the transductions, RFP+ cells were sorted, and total RNA of sorted cells was isolated and used for Affymetrix Exome arrays.
2012-09-09 | E-GEOD-40712 | biostudies-arrayexpress
Project description:Gene expression analyses of Tif1b, Hp1a or Hp1g knockdown hematopoietic progenitors. Growth of hematopoietic stem cells (HSCs) are significantly impaired upon knockdown of Hp1a and Hp1g. Results provide insight into the role of these factors in hematopoiesis. HSCs (CD34- c-Kit+ Sca1+ Lineage- ) were transduced with lentivirus expressing shRNA against Tif1b, Hp1a or Hp1g, and cultured for 14 days. Then, GFP+ c-Kit+ Lineage- hematopoietic progenitors were sorted and subjected into microarray analysis
2014-08-01 | E-GEOD-48897 | biostudies-arrayexpress
Project description:We performed morphogen-directed differentiation of human PSCs into HE followed by combinatorial screening of 26 candidate HSC-specifying TFs for the potential to promote hematopoietic engraftment in irradiated immune deficient murine hosts. We recovered seven TFs (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, SPI1) that together were sufficient to convert HE into hematopoietic stem and progenitor cells (HSPCs) that engraft primary and secondary murine recipients.
2017-05-17 | GSE83719 | GEO