The modulation of HIFs, pluripotency and differentiation genes expression by oxygen conditions in neural stem cells derived from human cord blood

• Autorzy: Szablowska-Gadomska I. , Drela K. , Podobinska M. , Ziemka-Nalecz M. , Domanska-Janik K. , Buzanska L.
• Języki publikacji: EN

Abstrakty

EN

The oxygen tension is an important factor modulating cell fate and developmental decisions. There are evidences that HIFs (Hypoxia Inducible Factors) family is implicated in the regulation of pluripotency and differentiation genes. The goal of this study is to compare the influence of close to physiological oxygen conditions (5%) to atmospheric oxygen tension on differentiation process and pluripotent activity in HUCB-NSC. The expression of Hypoxia Inducible Factors, stemness and neural differentiation markers in NSC, cultured under 5% and 21% oxygen were checked on the transcriptional and translational level. We were looking at the interaction between HIFs (HIF1 alpha, HIF 2 alpha) and activity of neural differentiations genes (MAP2, GFAP, β-tubulin) as well as expression of pluripotency genes (Oct4, Sox2, Rex1 and Nanog). In order to demonstrate the impact of increased HIF1α and/ or HIF2α level on cell differentiation we used DMOG (Sigma) which is of prolyl-4-hydroksylase inhibitor to increase HIF alpha levels. Our data show, that low oxygen conditions promote proliferation of HUCBNSC at early stage of development and can activate Oct4 and Nanog genes in HUCB-NSC. The time of cultivation of the cells in low oxygen conditions and the developmental stage of the cells are the important factors for the induction of the expression of “pluripotency” genes.Hypoxia Inducible Factors HIF 1α and HIF 2α, but not HIF3α are expressed in HUCB-NSC at all stages of development. During neuronal differentiation of HUCB-NSC by using dBcAMP, 5% oxygen level act synergistically, promoting further differentiation (enhanced MAP2 expression). Application of prolyl hydroxylase inhibitor – DMOG resulted in increased expression of HIF1α but not HIF2α and increased the expression of MAP2 (only in 21% oxygen conditions) referring to variants without DMOG. Sponsored by grant from Polish Ministry of Scientific Research and Higher Education No N N302 597838 and by NSC grant No 2011/01/B/NZ3/05401

Słowa kluczowe

EN

modulation; hypoxia inducible factor; HIF zob.hypoxia inducible factor; pluripotency; differentiation; gene expression; oxygen condition; neural stem cell; man; cord blood

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.183

Twórcy

autor

Szablowska-Gadomska I.

• NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Drela K.

• NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Podobinska M.

• NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Ziemka-Nalecz M.

• NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Domanska-Janik K.

• NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Buzanska L.

• NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland