Topic: Germ cell plasticity
Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O, Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T
Generation of pluripotent stem cells from neonatal mouse.
Cell 119: 1001-1012, 2004

During development, cell fate appears to go in "one-way direction" from an undifferentiated state to a differentiated state, like a ball rolling down the landscape as the famous illustration of Conrad H. Waddington. However, sometimes we have found that certain cells go back the route to acquire an undifferentiated state, especially in in vitro conditions. The paper that we will be discussing on November 11th reports the establishment of undifferentiated, pluripotent cell lines from a differentiated tissue: testis from a newborn mouse.

In mice, germ cells are derived from pluripotent embryonic cells by an inductive process during gastrulation. Through cellular interactions a population of cells is specified as primordial germ cells (PGCs), which are progenitors of all germ cells. PGCs actively migrate and colonize the developing gonads. In the gonads, PGCs initiate differentiation towards either a spermatogenic or an oogenic pathway, according the sex of the animal. The spermatogenic pathway involves the establishment of male germline stem (GS) cells, which is speciallized for producing a large number of sperm. A previous work of the authors had shown that under certain culture conditions, GS cells can proliferate for a long term without undergoing such differentiative cell division; i. e. they have "stopped" going their normal route. The paper by Kanatsu-Shinohara goes one step further, and demonstrates the generation of undifferentiated, pluripotent cells from GS cells of neonatal mouse testes; i. e. cells have "reversed" the developmental direction and gone back to a state similar to the pluripotent embryonic cells.

Previously, multipotentiality of germ cells has been shown in teratomas (cancer of germ cells) and the PGC culture, as described in the introduction. The authors claim that derivation of the pluripotent stem cell from GS cells is different from cases of teratomas and the PGC culture by several lines of evidence. We will look at the evidence and it's indication in the paper, and discuss whether or not germ cells possess an intrinsic property to acquire pluripotency. Furthermore, we would like to consider what we could do to show this intrinsic property more directly, using the knowledge and technology that are now available to us.