Role of NFKB2 on the early myeloid differentiation of CD34+ hematopoietic stem/progenitor cells


Autoria(s): MOLFETTA, Greice Andreotti De; ZANETTE, Dalila Luciola; PANEPUCCI, Rodrigo Alexandre; SANTOS, Anemarie Ramos Dinarte dos; SILVA JR., Wilson Araujo da; ZAGO, Marco Antonio
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2010

Resumo

To better understand the early events regulating lineage-specific hematopoietic differentiation, we analyzed the transcriptional profiles of CD34+ human hematopoietic stem and progenitor cells (HSPCs) subjected to differentiation stimulus. CD34+ cells were cultured for 12 and 40 h in liquid cultures with supplemented media favoring myeloid or erythroid commitment. Serial analysis of gene expression (SAGE) was employed to generate four independent libraries. By analyzing the differentially expressed regulated transcripts between the un-stimulated and the stimulated CD34+ cells, we observed a set of genes that was initially up-regulated at 12 h but were then down-regulated at 40 h, exclusively after myeloid stimulus. Among those we found transcripts for NFKB2, RELB, IL1B, LTB, LTBR, TNFRSF4, TGFB1, and IKBKA. Also, the inhibitor NFKBIA (IKBA) was more expressed at 12 h. All those transcripts code for signaling proteins of the nuclear factor kappaB pathway. NFKB2 is a subunit of the NF-kappa B transcription factor that with RELB mediates the non-canonical NF-kappa B pathway. Interference RNA (RNAi) against NFKB1, NFKB2 and control RNAi were transfected into bone marrow CD34+HSPC. The percentage and the size of the myeloid colonies derived from the CD34+ cells decreased after inhibition of NFKB2. Altogether, our results indicate that NFKB2 gene has a role in the early commitment of CD34+HSPC towards the myeloid lineage. (C) 2010 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.

Fundacao de Amparo a Pesquisa do Estadode Sao Paulo (FAPESP)[2002/08273-1]

Fundacao de Amparo a Pesquisa do Estadode Sao Paulo (FAPESP)[1998/14247-6]

CNPq, Brazil

Identificador

DIFFERENTIATION, v.80, n.4/Mai, p.195-203, 2010

0301-4681

http://producao.usp.br/handle/BDPI/24458

10.1016/j.diff.2010.07.004

http://dx.doi.org/10.1016/j.diff.2010.07.004

Idioma(s)

eng

Publicador

ELSEVIER SCI LTD

Relação

Differentiation

Direitos

restrictedAccess

Copyright ELSEVIER SCI LTD

Palavras-Chave #Hematopoietic stem/progenitor cells #Bone marrow #Myeloid differentiation #NFKB2 #siRNA #KAPPA-B PATHWAY #BIOLOGY #ACTIVATION #TOOL #Cell Biology #Developmental Biology
Tipo

article

original article

publishedVersion