Oct4 Expression Is Not Required for Mouse Somatic Stem Cell Self-Renewal

Abstract

The Pou domain containing transcription factor Oct4 is a well-established regulator of pluripotency in the inner cell mass of the mammalian blastocyst as well as in embryonic stem cells. While it has been shown that the Oct4 gene is inactivated through a series of epigenetic modifications following implantation, recent studies have detected Oct4 activity in a variety of somatic stem cells and tumor cells. Based on these observations it has been suggested that Oct4 may also function in maintaining self-renewal of somatic stem cells and, in addition, may promote tumor formation. We employed a genetic approach to determine whether Oct4 is important for maintaining pluripotency in the stem cell compartments of several somatic tissues including the intestinal epithelium, bone marrow (hematopoietic and mesenchymal lineages), hair follicle, brain, and liver. Oct4 gene ablation in these tissues revealed no abnormalities in homeostasis or regenerative capacity. We conclude that Oct4 is dispensable for both self-renewal and maintenance of somatic stem cells in the adult mammal.

Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

“…Importantly, NANOG also bound the Aurka promoter in keratinocytes (Fig. 5c), whereas it did not bind to an intronic Aurka region or to the Oct4 promoter, which is not active in somatic tissues 16 . As a positive control, we confirmed that NANOG binds the Oct4 promoter in ESCs (Fig.…”

“…Upon implantation, Nanog, Oct4 and Sox2 expression is silenced in the majority of tissues. OCT4 is not expressed in normal adult tissues, but it is a driving oncogene in germ cell tumours 15,16 . SOX2 is expressed in adult neural stem cells 17 and in specific epithelia, notably including the oesophagus and forestomach, where it plays a role in tissue homeostasis 18 .…”

The role of oxygen availability in embryonic development and stem cell function

“…In the adult, Oct4 is exclusively expressed in germ cells, and had been detected in stem-cell populations such as bone marrow multipotent adult progenitors, haematopoietic stem cells, and stem cells that reside in epidermal basal layers 78,79 . More recent studies demonstrate that OCT4 is essential for germ-cell maintenance, but dispensable for somatic stem-cell self-renewal 80,81 . The importance of strictly maintaining Oct4 expression levels has been demonstrated both in vitro and in vivo: even a two-fold change in OCT4 protein abundance can cause ES cells to lose pluripotency 82 , and ectopic Oct4 expression promotes epithelial dysplasia in transgenic mice 83 .…”

Very small embryonic-like (VSEL) stem cells in adult organs and their potential role in rejuvenation of tissues and longevity

“…Some of these cells were described as expressing transcription factors characteristic for ESCs such as Octamer-4 (Oct-4). However, since the normal genome contains several Oct-4 pseudogenes, the real Oct-4 expression and its potential role in adult somatic cells requires further study (Lengner et al, 2007).…”