EVI2B is a C/EBP alpha target gene required for granulocytic differentiation and functionality of hematopoietic progenitors

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00483248" target="_blank" >RIV/67985823:_____/17:00483248 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/17:00483248 RIV/00064203:_____/17:10362997 RIV/00216208:11130/17:10362997

Result on the web

<a href="http://dx.doi.org/10.1038/cdd.2017.6" target="_blank" >http://dx.doi.org/10.1038/cdd.2017.6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/cdd.2017.6" target="_blank" >10.1038/cdd.2017.6</a>

Result language

angličtina

Original language name

EVI2B is a C/EBP alpha target gene required for granulocytic differentiation and functionality of hematopoietic progenitors

Original language description

Development of hematopoietic populations through the process of differentiation is critical for proper hematopoiesis. The transcription factor CCAAT/enhancer binding protein alpha (C/EBP alpha) is a master regulator of myeloid differentiation, and the identification of C/EBPa target genes is key to understand this process. Here we identified the Ecotropic Viral Integration Site 2B (EVI2B) gene as a direct target of C/EBPa. We showed that the product of the gene, the transmembrane glycoprotein EVI2B (CD361), is abundantly expressed on the surface of primary hematopoietic cells, the highest levels of expression being reached in mature granulocytes. Using shRNA-mediated downregulation of EVI2B in human and murine cell lines and in primary hematopoietic stem and progenitor cells, we demonstrated impaired myeloid lineage development and altered progenitor functions in EVI2B-silenced cells. We showed that the compromised progenitor functionality in EvI2b-depleted cells can be in part explained by deregulation of cell proliferation and apoptosis. In addition, we generated an Evi2b knockout murine model and demonstrated altered properties of hematopoietic progenitors, as well as impaired G-CSF dependent myeloid colony formation in the knockout cells. Remarkably, we found that EVI2B is significantly downregulated in human acute myeloid leukemia samples characterized by defects in CEBPA. Altogether, our data demonstrate that EVI2B is a downstream target of C/EBPa, which regulates myeloid differentiation and functionality of hematopoietic progenitors.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cell Death and Differentiation

ISSN

1350-9047

e-ISSN

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Volume of the periodical

24

Issue of the periodical within the volume

4

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

705-716

UT code for WoS article

000397919400015

EID of the result in the Scopus database

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