Protein Network Promotes Pluripotency of Stem Cells
26 Dec, 2006 04:41 pm
A study published November 16 in Nature identifies a protein network that promotes the pluripotency of stem cells. The lead author, Jianlong Wang, of the studies answers our questions.
As the starting point of our mapping effort, we used a protein called Nanog , which was proved by other researchers to be fundamental for stem cell pluripotency. We not only identified those factors that are already known to play critical roles in the regulation of stem cell pluripotency, but numerous others whose functions are previously unknown and are just to be realized for their important roles in stem cell biology.
How did you obtain these proteins and adapt them to your purposes?
We cloned the gene (Nanog) out of mouse embryonic stem cells and tagged it. Then the tagged Nanog was removed from cells and any proteins attached to it (i.e., would-be interacting partners of Nanog) were simultaneously removed. Finally, these attached proteins were identified by a protein identification technology known as mass spectrometry.
To confirm that the proteins we identified function to maintain stem cell pluripotency, we then depleted levels of several proteins in embryonic stem cells and observed that stem cell state was either compromised or lost.
What are currently the major issues that are impeding the production of stem cells? And what makes Nanog and its partners so special to the production of stem cells?
Ethical controversy and reprogramming efficiency are the two major issues for the production of embryonic stem cells. In particular, to produce disease or patient specific stem cells for therapy (known as therapeutic cloning or somatic cell nuclear transfer (SCNT)) requires destruction of embryos; on the other hand, stem cell generation by fusion (between human ES cells and somatic cells) or direct conversion of somatic cells by the four defined factors (published study on mouse ES cells by a Japanese group)  is very inefficient.
Nanog has been demonstrated to promote transfer of pluripotency to somatic cells by cell fusion . Therefore, further understanding of the Nanog as well as the network of regulatory factors will refine this approach to reprogramming. This may ultimately lead to direct, efficient conversion of a somatic cell to a pluripotent state without recourse to nuclear transfer or cell fusion.
What are the weaknesses of this protein network?
This protein network is by no means complete (or “proteome-wide”). The protein landscape that regulates stem cell pluripotency remains largely unexplored, and further mapping efforts are required to complete this protein network at proteomic level.
Is this protein network going to solve the pluripotency problems of stem cells?
I wouldn’t say that. However, the map we developed will provide stem cell biologists with an important guide for future studies.
 Wang, J., Rao, S., Chu, J., Shen, X., Levasseur, D. Theunissen, T. and Orkin, S. A protein interaction network for pluripotency of embryonic stem cells. Nature 444, 364-368 (16 November 2006)
 Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse
embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-76
 Silva, J., Chambers, I., Pollard, S. & Smith, A. Nanog promotes transfer of
pluripotency after cell fusion. Nature 441, 997-1001 (2006).