Dataset Information

Regulation of adipose tissue stromal cells behaviors by endogenic Oct4 expression control.

ABSTRACT:

Background

To 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 conclusions

Here, 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.

SUBMITTER: Kim JH

PROVIDER: S-EPMC2747014 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Publications

Regulation of adipose tissue stromal cells behaviors by endogenic Oct4 expression control.

Kim Jung Hwan JH Jee Min Ki MK Lee So Young SY Han Tae Hee TH Kim Bong Sun BS Kang Kyung Sun KS Kang Soo Kyung SK

PloS one 20090924 9

<h4>Background</h4>To 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.<h4>Methodology/principal findings and conclusions</h4>Here, we dem ...[more]

PMID: 19777066

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Project description:BackgroundBreast cancer is the most frequently diagnosed cancer and a common cause of cancer-related death in women. It is well recognized that obesity is associated with an enhanced risk of more aggressive breast cancer as well as reduced patient survival. Breast adipose tissue-derived mesenchymal stromal/stem cells (bASCs) are crucial components of the tumor microenvironment. A key step initially involved in this process might be the de-differentiation of bASCs into tumor supporting phenotypes.MethodsIn the present work, we isolated bASCs from adipose tissues adjacent to the tumor (aT bASCs) from lean- (ln-aT bASCs, BMI ≤ 25) and breast cancer patients with obesity (ob-aT bASCs, BMI ≥ 35), and analyzed their phenotypes with functional assays and RNA sequencing, compared to their counterparts isolated from adipose tissues distant from the tumor (dT bASCs).ResultsWe show that ln-aT bASCs are susceptible to be transformed into an inflammatory cancer-associated phenotype, whereas ob-aT bASCs are prone to be cancer-educated into a myofibroblastic phenotype. Both ln-aT- and ob-aT bASCs compromise their physiological differentiation capacity, and upregulate metastasis-promoting factors. While ln-aT bASCs stimulate proliferation, motility and chemoresistance by inducing epithelial-mesenchymal transition of low malignant breast cancer cells, ob-aT bASCs trigger more efficiently a cancer stem cell phenotype in highly malignant breast cancer cells.ConclusionBreast cancer-associated bASCs are able to foster malignancy of breast cancer cells by multiple mechanisms, especially, induction of epithelial-mesenchymal transition and activation of stemness-associated genes in breast cancer cells. Blocking the de-differentiation of bASCs in the tumor microenvironment could be a novel strategy to develop an effective intervention for breast cancer patients.SignificanceThis study provides mechanistic insights into how obesity affects the phenotype of bASCs in the TME. Moreover, it highlights the molecular changes inside breast cancer cells upon cell-cell interaction with cancer-educated bASCs.

Dataset Information

Regulation of adipose tissue stromal cells behaviors by endogenic Oct4 expression control.

Background

Methodology/principal findings and conclusions

Publications

Regulation of adipose tissue stromal cells behaviors by endogenic Oct4 expression control.

Similar Datasets

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