Abstract
BackgroundTo clarify the role of the POU domain transcription factor Oct4 in Adipose Tissue Stromal Cells (ATSCs), we investigated the regulation of Oct4 expression and other embryonic genes in fully differentiated cells, in addition to identifying expression at the gene and protein levels. The ATSCs and several immature cells were routinely expressing Oct4 protein before and after differentiating into specific lineages.Methodology/Principal Findings and ConclusionsHere, we demonstrated the role of Oct4 in ATSCs on cell proliferation and differentiation. Exogenous Oct4 improves adult ATSCs cell proliferation and differentiation potencies through epigenetic reprogramming of stemness genes such as Oct4, Nanog, Sox2, and Rex1. Oct4 directly or indirectly induces ATSCs reprogramming along with the activation of JAK/STAT3 and ERK1/2. Exogenic Oct4 introduced a transdifferentiation priority into the neural lineage than mesodermal lineage. Global gene expression analysis results showed that Oct4 regulated target genes which could be characterized as differentially regulated genes such as pluripotency markers NANOG, SOX2, and KLF4 and markers of undifferentiated stem cells FOXD1, CDC2, and EPHB1. The negatively regulated genes included FAS, TNFR, COL6A1, JAM2, FOXQ1, FOXO1, NESTIN, SMAD3, SLIT3, DKK1, WNT5A, BMP1, and GLIS3 which are implicated in differentiation processes as well as a number of novel genes. Finally we have demonstrated the therapeutic utility of Oct4/ATSCs were introduced into the mouse traumatic brain, engrafted cells was more effectively induces regeneration activity with high therapeutic modality than that of control ATSCs. Engrafted Oct4/ATSCs efficiently migrated and transdifferentiated into action potential carrying, functionally neurons in the hippocampus and promoting the amelioration of lesion cavities.
Highlights
A critical regulator of stem cell pluripotency, Oct4 (POU domain transcription factor, Pou5f1) is highly expressed in the early stage of mammalian embryo and in the inner cell mass of the blastocyst
To clarify the role of Oct4 in adult cells, we investigated the regulation of Oct4 expression and other embryonic genes in fully differentiated cells, while identifying that it was expressed at the gene and protein levels in Adipose Tissue Stromal Cells (ATSCs)
We evaluated the expression of Oct4 (POU5F1) to determine whether exogenic Oct4 induced the expression of early developmental genes KLF4, Sox-2, Rex-1, Utf1, Dapp5, fibroblast growth factor 4 (FGF4), ERas, and Nanog in cultured ATSCs (Fig. 1E)
Summary
A critical regulator of stem cell pluripotency, Oct (POU domain transcription factor, Pou5f1) is highly expressed in the early stage of mammalian embryo and in the inner cell mass of the blastocyst. ES cells lose the capacity to maintain pluripotency upon knockdown of expression of these transcription factors by RNA interference It has been demonstrated by chromatin immunoprecipitation studies that Oct and Sox bind to a few thousand regulatory sites in the ES cell genome [3,4] and likely that many of these target genes play a modulating role in ES cell differentiation. To clarify the role of the POU domain transcription factor Oct in Adipose Tissue Stromal Cells (ATSCs), we investigated the regulation of Oct expression and other embryonic genes in fully differentiated cells, in addition to identifying expression at the gene and protein levels. The ATSCs and several immature cells were routinely expressing Oct protein before and after differentiating into specific lineages
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