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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Cell Death and Differentiation

ISSN

1350-9047

e-ISSN

—

Svazek periodika

24

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

705-716

Kód UT WoS článku

000397919400015

EID výsledku v databázi Scopus

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