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First published online August 30, 2007
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Submitted on May 8, 2007
Accepted on August 21, 2007

TISSUE-SPECIFIC STEM CELLS

Functional Similarities among Genes Regulated by OCT4 in Human Mesenchymal and Embryonic Stem Cells

Steven J. Greco 1*, Katherine Liu 2, Pranela Rameshwar 3

1 Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103., In partial fulfillment for a Ph.D. thesis.
2 Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103.
3 Department of Medicine, Division of Hematology/Oncology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103.

* To whom correspondence should be addressed. E-mail: rameshwa{at}umdnj.edu.


  Abstract

OCT4 is a master transcriptional regulator, which mediates pluripotency in embryonic stem cells (ESCs) through inhibition of tissue-specific and promotion of stem cell-specific genes. Suppression of OCT4, along with other regulators of pluripotency, such as SOX2 and NANOG, has been correlated with cell-fate specification and lineage-specific differentiation. Recent reports have shown the expression of OCT4 in adult mesenchymal stem cells (MSCs), but have not ascribed functional homology with ESCs. MSCs are mesoderm-derived cells, primarily resident in adult bone marrow (BM), which undergo lineage-specific differentiation to generate specialized cells such as stroma, fat, bone and cartilage. We have previously demonstrated the plasticity of MSCs through their ability to generate neuronal cells. Here, we show that OCT4 provides similar regulatory circuitries in human MSCs and ESCs, utilizing ChIP-DSL technology and loss of function studies. MSCs were found to express the embryonic transcription factors OCT4, NANOG and SOX2. In addition, OCT4 was found to: (1) target similar genes in MSCs and ESCs; (2) promote the expression of MSC-specific genes; and (3) regulate MSC cell cycle progression. The results suggest similar regulatory mechanisms for OCT4 in MSCs and ESCs, and have implications regarding MSC plasticity.

Key Words. OCT4, embryonic stem cell, mesenchymal stem cell, plasticity, ChIP-DSL




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