Advertisement

Topics

The transcriptional regulators CITED2 and PU.1 cooperate in maintaining hematopoietic stem cells.

08:00 EDT 12th April 2019 | BioPortfolio

Summary of "The transcriptional regulators CITED2 and PU.1 cooperate in maintaining hematopoietic stem cells."

Reduced expression of the transcription factor PU.1 is frequently associated with development of acute myeloid leukemia (AML), whereas elevated levels of CITED2 (CBP/p300-interacting-transactivator-with-an-ED-rich-tail 2) enhance maintenance of both normal and leukemic hematopoietic stem and progenitor cells (HSPCs). Recent findings indicated that PU.1 and CITED2 act in the same gene regulatory network and we therefore examined a potential synergistic effect of simultaneous PU.1 downregulation and CITED2 upregulation on stem cell biology and AML pathogenesis. We found that simultaneous PU.1/CITED2 deregulation in human CD34 cord blood (CB) cells, as well as CITED2 upregulation in preleukemic murine PU.1-knockdown (PU.1) bone marrow cells, significantly increased the maintenance of HSPCs compared to the respective deregulation of either factor alone. Increased replating capacity of PU.1/CITED2 cells in in vitro assays eventually resulted in outgrowth of transformed cells, while upregulation of CITED2 in PU.1 cells enhanced their engraftment in in vivo transplantation studies without affecting leukemic transformation. Transcriptional analysis of CD34 CB cells with combined PU.1/CITED2 alterations revealed a set of differentially expressed genes that highly correlated with gene signatures found in various AML subtypes. These findings demonstrate that combined PU.1/CITED2 deregulation induces a transcriptional program that promotes HSPC maintenance which might be a pre-requisite for malignant transformation.

Affiliation

Journal Details

This article was published in the following journal.

Name: Experimental hematology
ISSN: 1873-2399
Pages:

Links

DeepDyve research library

PubMed Articles [19649 Associated PubMed Articles listed on BioPortfolio]

Lrp5 and Lrp6 are required for maintaining self-renewal and differentiation of hematopoietic stem cells.

Hematopoietic stem cells (HSCs) have the capacity for self-renewal to maintain the HSCs' pool and the ability for multilineage differentiation, which are responsible for sustained production of multip...

Mechanism suppressing H3K9 trimethylation in pluripotent stem cells and its demise by polyQ-expanded huntingtin mutations.

Pluripotent stem cells are invaluable resources to study development and disease, holding a great promise for regenerative medicine. Here we use human embryonic stem cells (hESCs) and induced pluripot...

Non-thermal atmospheric pressure plasma is an excellent tool to activate proliferation in various mesoderm-derived human adult stem cells.

Adult stem cells are capable of self-renewal and differentiation into specific cell types in tissues and have high potential for stem cell therapy. Mesenchymal and hematopoietic stem cells are easily ...

Stem cell homeostasis by integral feedback through the niche.

Hematopoiesis is a paradigm for tissue development and renewal from stem cells. Experiments show that the maintenance of hematopoietic stem cells (HSCs) relies on signals from niche cells. However, it...

Spatiotemporal Resolution of SCF Supply in Early Hematopoiesis.

Evidence suggests that hematopoietic progenitor cells self-replenish in situ over prolonged time frames, centering the question on the identity and source of growth factors maintaining HPC fidelity. I...

Clinical Trials [9775 Associated Clinical Trials listed on BioPortfolio]

Thalassemia Treatment Based on the Stem Cell Technology

In order to study the transplantation effect of hematopoetic stem cells from beta-thalassemia induced pluripotent stem cells. We applied clinical grade source of autologous hematopoietic s...

Effect of NAC on the Hematopoietic Reconstitution After Haploidentical Hematopoietic Stem Cell Transplantation

The aim of the study is to evaluate the efficacy of the prophylactic administration of N-acetyl-L-cysteine (NAC) in acute leukemia patients with complete remission pre- and post-allotransp...

Hematopoietic Stem Cell Transplantation for the Treatment of Limb Ischemia and Diabetic Neuropathy

Several pathophysiological theories have been proposed for the development of diabetic chronic complications. In recent years, the use of stem cells (totipotential, hematopoietic or endoth...

A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies-Increasing GVT Effects Without Increasing Toxicity

This phase II trial studies the how well donor stem cell transplant works in treating patients with high risk hematologic malignancies. Giving total-body irradiation and chemotherapy befor...

Mesenchymal Stem Cell Infusion in Haploidentical Hematopoietic Stem Cell Transplantation in Patients With Hematological Malignancies

Mesenchymal stem cells (MSCs) have been used in the treatment and prevention of graft-versus host disease (GVHD). In this study the investigators aim to present the efficacy of mesenchymal...

Medical and Biotech [MESH] Definitions

Bipotential angio-hematopoietic stem cells that give rise to both HEMATOPOIETIC STEM CELLS and ENDOTHELIAL CELLS.

The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.

Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.

Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.

Transplantation of stem cells collected from the peripheral blood. It is a less invasive alternative to direct marrow harvesting of hematopoietic stem cells. Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Stem Cells
Track and monitor developments in stem cell research and commercial development.  Follow the tabs above to read the latest global news, research, clinical trials on stem cells and follow companies active in the stem cell industry.  BioPort...

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...


Searches Linking to this Article