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YOUR DAILY DOSE OF SCIENCE 3

FACTORS REQUIRED

TO GENERATE NAIVE STEM

CELLS BY REPROGRAMMING

HAS BEEN DISCOVERED

Researchers have identified factors
required to generate naive stem

cells by reprogramming.

Researchers from the aged to self-organize in pre-implantation embry- The team focused on Not only does this research
Babraham Institute’s Epi- particular conditions, they os, or more commonly one epigenetic complex improve scientists’ ability
genetics research program form structures that re- researchers expose primed in particular, the PRC1.3 to produce human naïve
have been able to learn semble an early blastocyst PSCs to conditions that complex, that regulates PSCs, it provides details
more about naïve stem cell stage of development. By induces them to become gene expression without on the molecular events
reprogramming following growing these cells in the naïve PSCs. Existing meth- altering the underlying that occur during the cell
a genome wide functional lab, we can learn about the ods for reprogramming DNA sequence, and which state transition itself, some
screen. Their research, key events that happen were inefficient and slow, they found to be essential of which are conserved in
published today in Sci- during human develop- preventing researchers’ for the formation of naïve developmental regulation
ence Advances, describes ment, and they have po- from quickly producing the PSCs. Without this com- in human embryos.
the critical regulators of tential uses in personalized numbers of high-quality plex, the cells undergoing
reprogramming and offers medicine. But we need to stem cells they needed. reprogramming become a The Rugg-Gunn lab are
opportunities for a more create high-quality, stable completely different type
efficient, faster way to stem cell populations to be Adam Bendall, PhD stu- of cell rather than naïve putting together the pieces
generate human naïve able to conduct our exper- dent and a lead researcher PSCs. This suggests that of a bigger puzzle — the
pluripotent stem cells. iments.” on the study, said: “Very lit- the activity of PRC1.3 could best understanding of the
tle was known about what encourage more cells to formation and control of
Human pluripotent stem Immunofluorescent mi- genetic and epigenetic reprogram properly, in ef- naïve stem cells. Their pre-
cells (PSCs) are a useful croscopy images show the factors are required for fect lowering the barrier. vious research has identi-
tool for researchers investi- different morphology of naïve cell reprogramming, fied molecular factors that
gating how cells specialize reprogrammed pluripo- and this knowledge gap After identifying factors help to maintain cells in a
to make every tissue of our tent stem cells (orange) limited the design of repro- that promote reprogram- naïve stage. Group leader,
body. They come in two dif- and cells that were not gramming conditions.” ming, the researchers also Peter Rugg-Gunn said: “By
ferent states, primed and reprogrammed (purple). looked at factors that building up our tools for
naïve. Both types of PSC Credit: Adam Bendall, PhD The low efficiency of naïve impede reprogramming, manipulating pluripotent
can self-renew and differ- student, The Babraham reprogramming suggests exemplified in their study stem cells, we can spend
entiate into new cell types Institute the presence of barriers by an epigenetic protein more time asking impor-
but they have distinct that limit cells in reaching called HDAC2. Dr. Amanda tant questions about the
functions and molecular Pluripotent stem cells the naïve state. Adam Collier, first author on the pre-implantation embryo.
characteristics. are formed either from and his colleagues honed paper, explained: “Excit- In the longer term, further
embryos or using Nobel in on these barriers by ingly, when we inhibited
Group leader Peter Prize-winning methods performing a large-scale one of these factors using improvements in working
Rugg-Gunn explained to remove cell identity genetic screen to identify selective chemicals, then with naïve PSCs might
the importance of these from specialized cells. The genes that hinder and help naïve PSC reprogramming open up the possibility for
cells: “Human PSCs in the majority of reprogramming reprogramming. They were occurred more efficiently using these cells in person-
naïve state replicate the experiments generate able to identify a large and rapidly. We’re able to alized disease models or
key molecular and cellular primed PSCs, which are number of genes that have look at it from both sides; cell therapies, although this
characteristics of cells in more developmentally a crucial role in naïve PSC we can remove the barriers will require more research
a pre-implantation stage advanced than naïve PSCs. programming that had not and introduce the factors on how to differentiate
embryo. Importantly, when Naïve PSCs can be col- been previously linked to that push cells towards naïve PSCs into specialized
naïve PSCs are encour- lected directly from human the process. state change.” cell types.”