The increasing momentum of stem cell research continues, with the better characterization of induced pluripotent stem (iPS) cells, the conversion of differentiated cells into different cell types and the use of pluripotent stem cells to generate whole tissues, among other advances. Here, six experts in the field of stem cell research compare different stem cell models and highlight the importance of pursuing complementary experimental approaches for a better understanding of pluripotency and differentiation and an informed approach to medical applications.
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E.P. is a California Institute for Regenerative Medicine (CIRM, San Francisco, California, USA) New Faculty member and a scholar of the The American Society of Hematology (ASH).
Shinya Yamanaka is a member without a salary of the scientific advisory boards of iPierian, Inc., iPS Academia Japan and Megakaryon Corporation. George Q. Daley holds stock options at iPierian, Inc., and he receives consulting fees. Cédric Blanpain, Konrad Hochedlinger, Emmanuelle Passegué and Janet Rossant declare no competing financial interests.
Structures that are formed during early embryogenesis in mammals. The fertilized embryo undergoes cleavage to produce blastomeres, which, after a fixed number of cell divisions, become compacted together. The outer cells form an epithelium (the trophoblast) that separates from the internal group of cells, which constitute the inner cell mass (ICM). The resulting structure comprising the trophoblast and the ICM is called the blastocyst.
The inner layer of the developing embryo that originates from the inner cell mass (ICM) and gives rise to the fetus.
A form of chromatin that is lightly packed and often transcriptionally active during interphase.
Highly compacted chromatin that is transcriptionally inactive. Includes structural regions of the chromosome that lack genes ('constitutive' heterochromatin, for example, centromeres) as well as genes that are silenced in a given cell type ('facultative' heterochromatin).
- Induced pluripotent stem cells
(iPS cells). Somatic cells that have been induced to become pluripotent through ectopic expression of four transcription factors — OCT4, SOX2, MYC and KLF4 (Krüppel-like factor 4).
- Naive state
A state of pluripotency in which cells are fully unrestricted and can give rise to all cell types of the embryo and later adult. This state is present only transiently during mammalian development, in the pre-implantation epiblast, and after culture of mouse embryonic stem cells in the presence of inhibitors of glycogen synthase kinase 3 (GSK3) and extracellular signal-regulated kinase (ERK).
Specialized microenvironment in which stem cells reside. The nice produces signals that regulate stem cell identity and maintenance.
- Nuclear transfer
An experimental method to reprogram differentiated cells back to pluripotency. In this method, mammalian somatic cell nuclei are transplanted into a previously enucleated oocyte (unfertilized egg).
A culture system in which the tissue, removed from an organ, continues to differentiate and develop as if it was in the original organ.
Transplantation of tissue or cells from a donor into its normal position in the body of the recipient.
- Reconstitution approaches
Differentiation of pluripotent stem cells into a tissue or an organ.
An encapsulated, non-malignant tumour that comprises tissue or organ components resembling normal derivatives of all three germ layers.
The use of transcription factors (and, in some cases, chemical factors) to convert a differentiated cell type into another differentiated cell type, even between developmentally distant cells (belonging to different germ layers): for example, the conversion of fibroblasts to neurons.
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