Faculty Collaboration Database

A protein interaction network for pluripotency of embryonic stem cells. Nature 2006 Nov 16;444(7117):364-8

Date

11/10/2006

Pubmed ID

17093407

DOI

10.1038/nature05284

Scopus ID

2-s2.0-33751092246 (requires institutional sign-in at Scopus site)   935 Citations

Abstract

Embryonic stem (ES) cells are pluripotent and of therapeutic potential in regenerative medicine. Understanding pluripotency at the molecular level should illuminate fundamental properties of stem cells and the process of cellular reprogramming. Through cell fusion the embryonic cell phenotype can be imposed on somatic cells, a process promoted by the homeodomain protein Nanog, which is central to the maintenance of ES cell pluripotency. Nanog is thought to function in concert with other factors such as Oct4 (ref. 8) and Sox2 (ref. 9) to establish ES cell identity. Here we explore the protein network in which Nanog operates in mouse ES cells. Using affinity purification of Nanog under native conditions followed by mass spectrometry, we have identified physically associated proteins. In an iterative fashion we also identified partners of several Nanog-associated proteins (including Oct4), validated the functional relevance of selected newly identified components and constructed a protein interaction network. The network is highly enriched for nuclear factors that are individually critical for maintenance of the ES cell state and co-regulated on differentiation. The network is linked to multiple co-repressor pathways and is composed of numerous proteins whose encoding genes are putative direct transcriptional targets of its members. This tight protein network seems to function as a cellular module dedicated to pluripotency.

Author List

Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, Orkin SH

Author

Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
DNA-Binding Proteins
Embryonic Stem Cells
Homeodomain Proteins
Humans
Immunoprecipitation
Mice
Multiprotein Complexes
Nanog Homeobox Protein
Pluripotent Stem Cells
Protein Binding
RNA Interference
Reproducibility of Results