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embryonic stem cells

Monday 1 December 2003

Mammalian development requires the specification of over 200 cell types from a single totipotent cell.

Extracellular signals and second messengers modulate cell-autonomous regulators such as OCT4, SOX2 and Nanog in a combinatorial complexity.

Knowledge of this circuitry might reveal how to achieve phenotypic changes without the genetic manipulation of OCT4, Nanog and other toti/pluripotency-associated genes.

The differentiation of embryonic stem (ES) cells is accompanied by activation and/or silencing of specific loci and global chromatin reorganization. Hyperdynamic association between the chromatin and the major proteins that determine its architecture is a hallmark of pluripotency, and that it is required for differentiation to occur.

SOXs and POUs

Combined action of SOXs and POUs families of transcription factors plays major roles in embryonic development.

In embryonic stem cells, the combination of SOX2 and POU5F1 (OCT3/4) is essential for maintaining the undifferentiated state by activating pluripotency-linked genes, and inhibition of genes involved in differentiation.

Besides embryonic stem cells, POU5F1 is also present in early germ cells, primordial germ cells, and gonocytes, where it has a role in suppression of apoptosis.

SOX2 is absent in germ cells of human fetal gonads, and as expected carcinoma in situ (CIS), ie the precursor lesion of testicular germ cell tumours of adolescents and adults (TGCTs), and seminoma.

Based on genome-wide expression profiling, SOX17 was found to be present, instead of SOX2, in early germ cells and their malignant counterparts, CIS and seminoma.

SOX17 is a suitable marker to distinguish seminoma from embryonal carcinoma, confirmed in representative cell lines.

Aberrant SOX2 expression can be present in Sertoli cells when associated with CIS, which can be misdiagnosed as embryonal carcinoma.

The absence of SOX2 in human embryonic and malignant germ cells, which express SOX17 in conjunction with POU5F1. This finding allows the identification of seminoma-like cells from embryonal carcinoma based on a positive marker and might be the explanation for the different function of POU5F1 in normal and malignant germ cells versus embryonic stem cells. (18348160)


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