Takashi Shinohara talks with
ScienceWatch.com and answers a few questions about
this month's Emerging Research Front Paper in the field of
Molecular Biology & Genetics.
Article: Generation of pluripotent
stem cells from neonatal mouse
testis
Authors: 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
Journal: CELL, 119 (7): 1001-1012 DEC 29 2004
Addresses: Kyoto Univ, Horizontal Med Res Org, Kyoto
6068501, Japan.
Kyoto Univ, Horizontal Med Res Org, Kyoto 6068501,
Japan.
(addresses have been truncated.)
Why do you think your paper is highly
cited?
This is probably because it was the first paper to show the derivation of
Embryonic Stem-like (ES-like) pluripotent cells (multipotent germline stem
cells, mGS cells) from postnatal animals.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
"We have made knockout mice using
these mGS
cells."
It's a discovery of a method that allows derivation of a new germ cell
line.
Would you summarize the significance of your paper in
layman's terms?
We showed that spermatogonial stem cells in postnatal animals can give rise
to ES-like cells. This still is the only way to derive pluripotent cells
without genetic treatment.
How did you become involved in this research and were
any particular problems encountered along the way?
This is a complete byproduct of our research on gene targeting experiments
using spermatogonial stem cells (SSCs). We first described our long-term
culture of SSCs in 2003. These cells, which we named "Germline Stem" (GS)
cells, can make sperm in the testis after microinjection into seminiferous
tubules. Using these cells, we made knockout mice in 2006.
In the course of these knockout mouse experiments, we noticed ES-like
colonies in the GS cell culture. Although we initially thought that they
came from embryonic fibroblasts that were used in GS cell culture, it
turned out that the cells were coming directly from testis cells.
This was totally unexpected, because people have assumed that these
germline cells lose pluripotency in midgestation.
Where do you see your research leading in the
future?
We have made knockout mice using these mGS cells. We are now trying to
increase the efficiency of derivation and extend this technique to other
animal species.
Do you foresee any social or political implications for
your research?
Because induced pluripotent stem cells, commonly abbreviated as iPS cells
or iPSCs, need exogenous genes to maintain their pluripotency, people have
been looking for methods to derive iPS cells without viruses. In this
sense, mGS cells can be derived without any genetic treatment and, with
these efforts continuing into the future, researchers will eventually
establish similar cells from human testes.
Takashi Shinohara, Professor
Department of Molecular Genetics
Graduate School of Medicine
Kyoto University
Kyoto, Japan