TY - JOUR
T1 - Recent insights into the naïve state of human pluripotency and its applications
AU - Dong, Chen
AU - Fischer, Laura A.
AU - Theunissen, Thorold W.
N1 - Funding Information:
We thank Angela Bowman, Lilianna Solnica-Krezel, and members of the Theunissen lab for critical reading of the manuscript, and Steven Lee for assistance with scientific illustrations. Funding for our research is provided by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital, as well as the McDonnell Center for Cellular and Molecular Neurobiology.
Funding Information:
We thank Angela Bowman, Lilianna Solnica-Krezel, and members of the Theunissen lab for critical reading of the manuscript, and Steven Lee for assistance with scientific illustrations. Funding for our research is provided by the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital , as well as the McDonnell Center for Cellular and Molecular Neurobiology .
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The past decade has seen significant interest in the isolation of pluripotent stem cells corresponding to various stages of mammalian embryonic development. Two distinct and well-defined pluripotent states can be derived from mouse embryos: “naïve” pluripotent cells with properties of pre-implantation epiblast, and “primed” pluripotent cells, resembling post-implantation epiblast. Prompted by the successful interconversion between these two stem cell states in the mouse system, several groups have devised strategies for inducing a naïve state of pluripotency in human pluripotent stem cells. Here, we review recent insights into the naïve state of human pluripotency, focusing on two methods that confer defining transcriptomic and epigenomic signatures of the pre-implantation embryo. The isolation of naïve human pluripotent stem cells offers a window into early developmental mechanisms that cannot be adequately modeled in primed cells, such as X chromosome reactivation, metabolic reprogramming, and the regulation of hominid-specific transposable elements. We outline key unresolved questions regarding naïve human pluripotency, including its extrinsic and intrinsic control mechanisms, potential for embryonic and extraembryonic differentiation, and general utility as a model system for human development and disease.
AB - The past decade has seen significant interest in the isolation of pluripotent stem cells corresponding to various stages of mammalian embryonic development. Two distinct and well-defined pluripotent states can be derived from mouse embryos: “naïve” pluripotent cells with properties of pre-implantation epiblast, and “primed” pluripotent cells, resembling post-implantation epiblast. Prompted by the successful interconversion between these two stem cell states in the mouse system, several groups have devised strategies for inducing a naïve state of pluripotency in human pluripotent stem cells. Here, we review recent insights into the naïve state of human pluripotency, focusing on two methods that confer defining transcriptomic and epigenomic signatures of the pre-implantation embryo. The isolation of naïve human pluripotent stem cells offers a window into early developmental mechanisms that cannot be adequately modeled in primed cells, such as X chromosome reactivation, metabolic reprogramming, and the regulation of hominid-specific transposable elements. We outline key unresolved questions regarding naïve human pluripotency, including its extrinsic and intrinsic control mechanisms, potential for embryonic and extraembryonic differentiation, and general utility as a model system for human development and disease.
KW - Lineage potential
KW - Naive pluripotency
KW - Reprogramming
KW - Transposable elements
KW - X chromosome inactivation
UR - http://www.scopus.com/inward/record.url?scp=85073079082&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2019.111645
DO - 10.1016/j.yexcr.2019.111645
M3 - Article
C2 - 31585117
AN - SCOPUS:85073079082
SN - 0014-4827
VL - 385
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
M1 - 111645
ER -