Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enforced Expression of NUP98-HOXA10hd Fusion Gene in Multipotent Progenitors Support Long-term Hematopoiesis in primary mice [MP]

ABSTRACT: Allogenic hematopoietic stem cell (HSC) transplantation is widely used for treatment of blood disorders to re-establish long-term multi-lineage hematopoiesis. Enhance self-renewal potential of progenitor population to support hematopoiesis offer an alternative and complementary approach to achieve similar therapeutic effects. Nup98-Hoxa10hd fusion gene (NA) has been shown to confer expansion, anti-stress response and engraftment competitiveness on HSC. However, whether the ectopic expression of NA in multipotent progenitors (MPPs) could enhance their self-renewal potential and confer long-term multi-lineage hematopoiesis remains unknown. In this study, we showed that ectopic expression in MPPs confer long-term multi-lineage hematopoiesis in recipient mice. We further showed that NA upregulated pathways of cell cycle regulation, epigenetic regulation and response to stress in MPPs. These molecular traits increased the self-renewal potential of NA MPPs, which resulting in production of lineage-maintaining committed progenitor cells. Transcriptome analysis of NA myeloid progenitors identified genes regulating hematopoiesis, homeostasis, phosphorylation. In summary, we show that ectopic expression of Nup98-Hoxa10hd fusion gene enhance self-renwal potential of MPPs thus confer long-term multilineage repopulating capacity on MPPs, offering promising means to involve MPPs to augment cell source in clinical transplantation settings.

ORGANISM(S): Mus musculus

PROVIDER: GSE146779 | GEO | 2020/10/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Enforced Expression of NUP98-HOXA10hd Fusion Gene in Multipotent Progenitors Support Long-term Hematopoiesis in primary mice [MPP]

Project description:Allogenic hematopoietic stem cell (HSC) transplantation is widely used for treatment of blood disorders to re-establish long-term multi-lineage hematopoiesis. Enhance self-renewal potential of progenitor population to support hematopoiesis offer an alternative and complementary approach to achieve similar or enhance therapeutic effects. Nup98-Hoxa10hd fusion gene (NA) has been shown to confer expansion, anti-stress response and engraftment competitiveness on HSC. However, whether the ectopic expression of NA in multipotent progenitors (MPPs) could enhance their self-renewal potential and confer long-term multi-lineage hematopoiesis remains unknown. In this study, we showed that ectopic expression in MPPs confer long-term multi-lineage hematopoiesis in recipient mice. We further showed that NA upregulated pathways of cell cycle regulation, epigenetic regulation and response to stress in MPPs. These molecular traits increased the self-renewal potential of NA MPPs, which resulting in production of lineage-maintaining committed progenitor cells. Transcriptome analysis of NA myeloid progenitors identified genes regulating hematopoiesis, homeostasis, phosphorylation. In summary, we show that ectopic expression of Nup98-Hoxa10hd fusion gene enhance self-renewal potential of MPPs thus confer long-term multi-lineage repopulating capacity on MPPs, offering promising means to involve MPPs to augment cell source in clinical transplantation settings.

2020-10-06 | GSE146780 | GEO

Synergy of Nras mutation and Nup98-Hoxa10HD gene fusion efficiently preserves the stemness of single hematopoietic stem cells after feeder-free culture

Project description:Hematopoietic stem cell (HSC) gives rise to all the hematopoietic cells. The stemness of HSC is strictly controlled by some transcription factors. Here we show that both of Nras mutation (NrasG12D) and Nup98-Hoxa10HD (NA) improve the transplantation competition ability of HSC. Pathways and differential expression genes analysis show that NrasG12D and NA proteins enhance the competitiveness of HSCs via distinct signaling mechanisms.

2019-08-27 | GSE118809 | GEO

transcriptional profiling of NUP98-CDX1, NUP98-CDX4 and EGFP overexpressing primitive mouse bone marrow cells

Project description:The first genetic hits towards leukemia are thought often to confer to the mutant clone a slight proliferative/survial advantage. These pre-malignant clones can then be maintained under physiological cues in normal pool for long periods. We have searched for this type of first genetic hits and found that ectopic expression of novel nucleoporin 98 (NUP98)-homeodomain fusion proteins in primitive bone marrow cells can induce long-lasting hematopoietic stem cell (HSC) activity in these cells. More specifically, NUP98-CDX1/2 was able to sustain HSC activity with high frequencies despite massive in vitro expansions and in vivo residence. Continual expression of NUP98-CDX1/2 did not perturb lymphoid, myeloid or erythroid/platelet differentiation and NUP98-CDX1/2 was able to reprogram committed progenitors into cells with attributes of HSC. Switching off of NUP98-CDX1/2 expression did not lead to “return” to normal HSC but acute differentiation. Related NUP98-CDX4 induced leukemia with the shortest latency ever reported for HOX transcription factors. In this case switching off of NUP98-CDX4 expression cured the full-blown leukemia and again the cured cells showed only transient repopulating activity in vivo. These two types of pre-leukemic cells generated here will provide useful models for elucidating the self-renewal mechanisms of HSC as well as leukemic stem cells. Total RNA from NUP98-CDX lines was compared to EGFP overexpressing lines. The experiment was done in triplicate.

2012-12-01 | E-GEOD-37900 | biostudies-arrayexpress

Tet1 is a tumor suppressor of hematopoietic maligancy [RNA-Seq]

Project description:Loss of Tet1 expression causes global 5mC and 5hmC changes in stem and progenitor cells in mice and enhanced pro-B cell self-renewal, increased DNA damage and B-lymphomageneis. In this study we performed whole transciptome analysis using RNA-sequencing in purified long-term HSCs and MPPs. These results revealed that genes regulated byTet1 included Histones, DNA repair enzymes and B-lineage specific factors. Purified long-term HSCs and MPPs from WT and Tet1 KO mice were used for RNA isolation. RNA was extracted using RNeasy kit (Qiagen) and PolyA selection using oligo-dT beads (Life Technologies) was performed according to the manufacturer’s instructions. Libraries were generated as described before, including end-repair, A-tailing, adapter (Illumina Truseq system) ligation and PCR amplification. RNA libraries were then sequenced on the Illumina HiSeq 2000 using 50bp paired-end reads. Transcriptome profiling of LT-HSC and MPP cells in WT and Tet1 KO mice

2015-04-12 | E-GEOD-65955 | biostudies-arrayexpress

Tet1 is a tumor suppressor of hematopoietic maligancy [RNA-Seq]

2015-04-12 | GSE65955 | GEO

transcriptional profiling of NUP98-CDX1, NUP98-CDX4 and EGFP overexpressing primitive mouse bone marrow cells

2012-12-01 | GSE37900 | GEO

Clonal analysis of lineage fate in unperturbed hematopoiesis

Project description:The classical tenet of hematopoiesis posits well-accepted lineage trees that arise from progressively restricted oligopotent and unipotent progenitor populations. However, because fate in hematopoiesis has mostly been studied in the context of transplantation, it is unclear whether these lineage branches and such proposed oligopotent progenitors exist in an unperturbed hematopoietic system. Here, we utilize endogenous transposon tagging to trace the fate of thousands of progenitors and stem cells over time to re-evaluate these dogmas. Our results describe a novel clonal roadmap where the megakaryocyte lineage arises independently of lymphoid and myeloid/erythroid fates. Our data also demonstrate that true oligopotency is largely restricted to the multipotent progenitor (MPP) compartment. Analysis of thousands of stem cell and progenitor transcriptomes demonstrates that lineage determination starts at the MPP stage and identifies a functional hierarchy within this population that drives hematopoiesis. Finally, our results demonstrate that long-term hematopoietic stem cells behave physiologically as megakaryocyte lineage progenitors. Our data provide evidence for a substantially revised hematopoietic roadmap, and highlights unique properties of MPPs and HSCs in situ.

2018-01-03 | GSE90742 | GEO

miR-125a Confers Multi-Lineage Long-Term Repopulating Stem Cell Activity to Murine and Human Hematopoietic Progenitors

Project description:Umbilical cord blood (CB) is a non-invasive, convenient and broadly used source of hematopoietic stem cells (HSCs) for allogeneic stem cell transplantation. However, limiting numbers of HSCs remain a major constraint for its clinical application. One feasible option would be to expand HSCs to improve therapeutic outcome, however available protocols and the molecular mechanisms governing the self-renewal of HSC are unclear. Here we show that ectopic expression of a single miRNA, miR-125a, in purified murine and human multipotent progenitors (MPP) resulted in increased self-renewal and robust long-term multi-lineage repopulation in transplanted recipient mice. Using quantitative proteomics and Western blot analysis, we identified a restricted set of miR-125a targets which revealed the involvement of the MAP kinase signaling pathway in conferring long-term repopulating capacity to multipotent progenitors in human and mice. Our findings offer the innovative potential to use MPP with enhanced self-renewal activity to augment limited sources of HSC to improve clinical protocols.

2017-01-11 | PXD003931 | Pride

Novel selective regulation of hematopoietic progenitor self-renewal, survival and proliferation by estrogens has therapeutic potential in myeloproliferative neoplasms

Project description:Estrogens are potential regulators of the hematopoietic stem cell (HSC) niche and have effects on mature hematopoietic cells; however, whether estrogen signaling directly regulates normal and malignant HSC remains unclear. We demonstrate differential expression and specific roles of estrogen receptors (ER) in hematopoietic progenitors. ERa activation in short-term HSC and multipotent progenitors induced apoptosis. In contrast, the selective ER modulator (SERM) tamoxifen induced proliferation of quiescent long-term HSC, altered their self-renewal signature and compromised hematopoietic reconstitution following myelotoxic stress. Treatment with tamoxifen alone abolished hematopoietic progenitor expansion induced by JAK2V617F by restoring normal levels of apoptosis, blocked JAK2V617F-induced myeloproliferative neoplasm in vivo, and sensitized MLL-AF9+ leukemias to chemotherapy. Tamoxifen showed selective effects on mutant cells compared to normal ones, and had only a minor impact on steady-state hematopoiesis in disease-free animals. These results uncover specific regulation of hematopoietic progenitors by estrogens and potential anti-leukemic properties of SERM LT-HSCs, ST-HSCs and MPPs sorted from the bone marrow of mice treated with tamoxifen or vehicle (3 biological replicates per group)

2014-12-04 | E-GEOD-62621 | biostudies-arrayexpress

Dynamics of Chromatin Accessibility during Hematopoietic Stem Cell Differentiation into Lineage-Committed Progeny

Project description:Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Our recent work revealed evidence of multilineage gene priming in HSCs, where open cis-regulatory elements (CREs) exclusively shared between HSCs and unipotent lineage cells were enriched for DNA binding motifs of known lineage-specific transcription factors. To test the hypothesis that HSC-primed lineage-specific CREs remain accessible throughout differentiation, we used ATAC-seq to map the temporal dynamics of chromatin remodeling during blood cell differentiation. We observed epigenetic-driven clustering of oligopotent and unipotent progenitors into distinct erythromyeloid and lymphoid branches, with multipotent HSCs and MPPs associating with the erythromyeloid lineage. We mapped the dynamics of lineage-primed CREs throughout hematopoiesis and identified both unique and shared CREs as potential lineage reinforcement mechanisms at fate branch points in hematopoiesis. These findings provide insight into the regulation of stem cell multipotency and lineage commitment throughout hematopoiesis and serve as a resource to test functional drivers of hematopoietic lineage fate.

2023-03-30 | GSE184851 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data