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cluster that is responsible for the 2009 modularity change is Cluster #7 induced
pluripotent stem cell (iPSC). On the one hand, the cluster contains Takahashi 2006
and Takahashi 2007, which pioneered the human iPSCs trend. On the other hand,
the cluster contains many recent publications. The average age of the articles in
this cluster is 2008. Therefore, we examine the members of this cluster closely,
especially focusing on 2009 publications.
The impact of Takahashi 2006 and Takahashi 2007 is so profound that their
citation rings would overshadow all other members in Cluster #7. After excluding
the display of their overshadowing citation rings, it becomes apparent that this
cluster is full of articles with citation bursts, which are shown as citation rings in
red. We labeled the ones published in 2009 and also two 2008 articles and one 2010
article (Fig.
8.2
and Table
8.8
).
The pioneering reprogramming methods introduced by Takahashi 2006 and
Takahashi 2007 modify adult cells to obtain properties similar to embryonic stem
cells using a cancer-causing oncogene c-Myc as one of the defined factors and a
virus to deliver the genes into target cells (Nakagawa et al.
2008
). It was shown
later on that c-Myc is not needed. The use of viruses as the delivery vehicle raised
safety concerns of its clinical implications in regenerative medicine because viral
integration into target cells' genome might activate or inactivate critical host genes.
Searching for virus-free techniques motivated a series of such studies, leading by an
article (Okita et al.
2008
) appeared on October 9, 2008.
What many of these 2009 articles have in common appear to be the focus on
improving previous techniques of reprogramming human somatic cells to regain a
pluripotent state. It was realized that the original method used to induce pluripotent
stem cells has a number of possible drawbacks associated with the use of viral
reprogramming factors. Several subsequent studies investigated alternative ways
to induce pluripotent stem cells with lower risks or improved certainty. These
articles were published within a short period of time. For instance, Woltjen 2009
demonstrated a virus-independent simplification of induced pluripotent stem cell
production. On March 26, 2009, Yu et al.'s article demonstrated that reprogramming
human somatic cells can be done without genomic integration or the continued
presence of exogenous reprogramming factors. On April 23, 2009, Zhou et al.'s
article demonstrated how to avoid using exogenous genetic modifications by
delivering recombinant cell-penetrating reprogramming proteins directly into target
cells. Soldner 2009 reported a method without using viral reprogramming factors.
Kaij reported a virus-free pluripotency induction method. On May 28, 2009, Kim
et al.'s article introduced a method of direct delivery of reprogramming proteins.
Vierbuchen 2010 is one of the few most recent articles that are found to have
citation bursts. The majority of the 2009 articles with citation bursts focused
on reprogramming human somatic cells to an undifferentiated state. In contrast,
Vierbuchen 2010 expanded the scope of reprogramming by demonstrating the
possibility of converting fibroblasts to functional neurons directly (Fig.
8.8
).
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