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

Autor(es)

De Molfetta, Greice Andreotti ^{[1, 2]} ; Zanette, Dalila Luciola ^[1] ; Panepucci, Rodrigo Alexandre ^[1] ; Dinarte dos Santos, Anemarie Ramos ^[1] ; da Silva, Jr., Wilson Araujo ^{[1, 2]} ; Zago, Marco Antonio ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ctr Blood, Ctr Cell Therapy, BR-14051140 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Genet, BR-14051140 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Clin Med, BR-14051140 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: DIFFERENTIATION; v. 80, n. 4-5, p. 195-203, NOV-DEC 2010.
• Citações Web of Science: 12

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. (AU)

• Processo FAPESP: 02/08273-1 - Análise da expressão gênica da fase inicial de diferenciação de células CD34+ utilizando a análise serial da expressão gênica (SAGE)
• Beneficiário: Greice Andreotti de Molfetta
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 98/14247-6 - Center for Research on Cell-Based Therapy
• Beneficiário: Marco Antonio Zago
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs