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Establishment of trophoblast stem cells under defined culture conditions in mice.
- Source :
-
PloS one [PLoS One] 2014 Sep 09; Vol. 9 (9), pp. e107308. Date of Electronic Publication: 2014 Sep 09 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- The inner cell mass (ICM) and trophoblast cell lineages duet early embryonic development in mammals. After implantation, the ICM forms the embryo proper as well as some extraembryonic tissues, whereas the trophoectoderm (TE) exclusively forms the fetal portion of the placenta and the trophoblast giant cells. Although embryonic stem (ES) cells can be derived from ICM in cultures of mouse blastocysts in the presence of LIF and/or combinations of small-molecule chemical compounds, and the undifferentiated pluripotent state can be stably maintained without use of serum and feeder cells, defined culture conditions for derivation and maintenance of undifferentiated trophoblast stem (TS) cells have not been established. Here, we report that addition of FGF2, activin A, XAV939, and Y27632 are necessary and sufficient for derivation of TS cells from both of E3.5 blastocysts and E6.5 early postimplantation extraembryonic ectoderm. Moreover, the undifferentiated TS cell state can be stably maintained in chemically defined culture conditions. Cells derived in this manner expressed TS cell marker genes, including Eomes, Elf5, Cdx2, Klf5, Cdh1, Esrrb, Sox2, and Tcfap2c; differentiated into all trophoblast subtypes (trophoblast giant cells, spongiotrophoblast, and labyrinthine trophoblast) in vitro; and exclusively contributed to trophoblast lineages in chimeric animals. This delineation of minimal requirements for derivation and self-renewal provides a defined platform for precise description and dissection of the molecular state of TS cells.
- Subjects :
- Activins pharmacology
Amides pharmacology
Animals
Blastocyst drug effects
Blastocyst metabolism
Blastocyst physiology
Cell Differentiation drug effects
Cell Differentiation physiology
Cell Lineage drug effects
Cell Lineage physiology
Ectoderm drug effects
Ectoderm metabolism
Ectoderm physiology
Embryo Implantation drug effects
Embryo Implantation physiology
Embryonic Development drug effects
Embryonic Development physiology
Embryonic Stem Cells metabolism
Female
Fibroblast Growth Factor 2 pharmacology
Heterocyclic Compounds, 3-Ring pharmacology
Humans
Mice
Placenta metabolism
Placenta physiology
Pregnancy
Pyridines pharmacology
Trophoblasts metabolism
Culture Media metabolism
Embryonic Stem Cells drug effects
Embryonic Stem Cells physiology
Trophoblasts drug effects
Trophoblasts physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25203285
- Full Text :
- https://doi.org/10.1371/journal.pone.0107308