Pluripotency Regulators in Human Mesenchymal Stem Cells: Expression of NANOG But Not of OCT-4 and SOX-2

Abstract

Mesenchymal stem cells (MSCs) are adult multipotent cells able to differentiate toward mature mesodermal lineages. In spite of more than a decade of investigation, little is known about the molecular mechanisms regulating the undifferentiated state and the identity of distinct functional subpopulations in these cells. Transcription factors that regulate the maintenance of the pluripotent state in embryonic stem cells, including NANOG, SOX2, and OCT4, have been proposed to play a similar role also in adult stem cells, although with conflicting results. We performed a critical evaluation of expression of these 3 transcription factors and found that NANOG, but not OCT-4 and SOX-2, is expressed in cultured human adult MSCs. Actually, NANOG was not expressed in freshly isolated MSCs, but was detected only after in vitro culture. NANOG was detected only in proliferating cells, but not in MSCs induced to differentiate. The percentage of cells expressing NANOG was maintained throughout early passages of MSCs, but then started to decrease in late passages in MSCs from adipose tissue and heart but not from bone marrow. However, the number of NANOG-expressing cells did not associate with the proliferative and differentiative capabilities of MSC populations, neither its expression appeared to identify cells having stem or progenitor cell properties. Accordingly, we propose that activation of NANOG expression in MSCs is associated with, although cannot directly regulate, the transition from in vivo quiescence to adaptation to in vitro growth conditions.

Potently Immunosuppressive 5-Fluorouracil–Resistant Mesenchymal Stromal Cells Completely Remit an Experimental Autoimmune Disease

“…In contrast, characterization of pluripotent markers in both untreated MSCs and 5-FU-MSCs showed expression of Nanog but not Oct-3/4. This is in agreement with past reports that MSCs express Nanog but not Oct-3/4 (16,30).…”

In Vivo Identity of Tendon Stem Cells and the Roles of Stem Cells in Tendon Healing

“…The lack of expression of these pluripotency markers in intact patellar tendon suggested that immunohistochemical staining of these markers was not suitable for the detection of tendon stem cell in intact tendon in situ. The activation of Oct4, Nanog, Sox2, and nucleostemin as well as CD146 after tendon injury might be related to the functions of these proteins in regulating self-renewal, cell proliferation, differentiation, and/or angiogenesis [28][29][30][31][32].…”

“…TDSCs expressed Nanog, Oct4, Sox2, and nucleostemin that were not observed in LRCs in intact tendon in vivo. The isolation of LRCs induced trauma to tendon, and this might trigger processes similar to tendon injury [28]. The expression of pluripotency markers and pericyte-related markers after …”

Mesenchymal Stem Cells in CNS Regeneration

“…Such a surprising high plasticity of MSCs might be explained by the expression of a variety of gene families in undifferentiated MSCs. Several recent studies have shown that MSCs express several embryonic stem cell markers (pluripotent markers) such as Oct4, Nanog, alkaline phosphatase and SSEA-4, and SOX2 (Park & Patel, 2010;Pierantozzi et al, 2011;Riekstina et al, 2009). It also has been demonstrated that the translational and transcriptional machinery in MSCs responsible for the expression of multiple genes typical of several derivatives of three germ layers are not silenced, rather operating at the low level (Blondheim et al, 2006;Tondreau et al, 2008).…”