Nanog is a Master Controller of ES cell Pluripotency

Mon, 03/04/2013 - 09:49

Nanog, a homeodomain (HD) transcription factor, plays a critical role in the maintenance of embryonic stem (ES) cell self-renewal. Transcription regulator involved in inner cell mass and ES cell proliferation and self-renewal. Imposes pluripotency on ES cells and prevents their differentiation towards extra embryonic endoderm and trophectoderm lineages (1).  Blocks bone morphogenetic protein-induced mesoderm differentiation of ES cells by physically interacting with SMAD1 and interfering with the recruitment of co-activators to the active SMAD transcriptional complexes. Nanog also acts as a transcriptional activator or repressor and is expressed in testicular carcinoma and derived germ cell tumors (at protein level). Nanog has been reported to be expressed in fetal gonads, ovary and testis and in ovary teratocarcinoma cell line and testicular embryonic carcinoma (2).

IHC analysis of Nanog in mouse teratoma. IHC analysis of Nanog in mouse teratoma.

Elevated levels of Nanog can maintain the mouse ES cell self-renewal independent of leukemia inhibitory factor (LIF) and enable human ES cell growth without feeder cells. In addition to the external signal pathways, intrinsic transcription factors such as FoxD3, P53 and Oct4 are also involved in regulating the expression of Nanog. Functionally, Nanog works in conjunction with other key pluripotent factors such as Oct4 and Sox2 to control a set of target genes that have important functions in ES cell pluripotency. These key factors form a regulatory network to support or limit each other's expression level, which maintains the properties of ES cells (3). The expanded regulatory network of Nanog and its partners forms the basis for further studies of directed differentiation and lineage reprogramming, and a paradigm for comprehensive elucidation of regulatory pathways in other stem cells and is an open area of investigation by several researchers.

  1. PMID: 16391521
  2. PMID: 12787504
  3. PMID: 17211451

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