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Project description:Human embryonic stem cells (hESCs) readily differentiate to somatic or germ lineages but have impaired ability to form extra-embryonic lineages such as placenta or yolk sac. Here, we demonstrate that naive hESCs can be converted into cells that exhibit the cellular and molecular phenotypes of human trophoblast stem cells (hTSCs) derived from human placenta or blastocyst. The resulting "transdifferentiated" hTSCs show reactivation of core placental genes, acquisition of a placenta-like methylome, and the ability to differentiate to extravillous trophoblasts and syncytiotrophoblasts. Modest differences are observed between transdifferentiated and placental hTSCs, most notably in the expression of certain imprinted loci. These results suggest that naive hESCs can differentiate to extra-embryonic lineage and demonstrate a new way of modeling human trophoblast specification and placental methylome establishment.
| S-EPMC7363941 | biostudies-literature
Project description:Human embryonic stem cells (hESCs) readily differentiate to somatic or germ lineages but have impaired ability to form extra-embryonic lineages such as placenta or yolk sac. Here we demonstrate that hESCs cultured in naïve media conditions can be converted into cells that exhibit the cellular and molecular phenotypes of human trophoblast stem cells (hTSCs) derived from human placenta or blastocyst. The resulting “transdifferentiated” hTSCs show reactivation of core placental genes, acquisition of a placenta-like methylome, and the ability to differentiate to extravillous trophoblasts and syncytiotrophoblasts. Modest differences are observed between transdifferentiated and placental hTSCs, most notably in the expression of certain imprinted loci. These results indicate that naïve hESCs can differentiate to extra-embryonic lineage, and demonstrate a new way of modeling human trophoblast specification and placental methylome establishment.
2020-06-16 | GSE152101 | GEO
Project description:Human embryonic stem cells (hESCs) readily differentiate to somatic or germ lineages but have impaired ability to form extra-embryonic lineages such as placenta or yolk sac. Here we demonstrate that hESCs cultured in naïve media conditions can be converted into cells that exhibit the cellular and molecular phenotypes of human trophoblast stem cells (hTSCs) derived from human placenta or blastocyst. The resulting “transdifferentiated” hTSCs show reactivation of core placental genes, acquisition of a placenta-like methylome, and the ability to differentiate to extravillous trophoblasts and syncytiotrophoblasts. Modest differences are observed between transdifferentiated and placental hTSCs, most notably in the expression of certain imprinted loci. These results indicate that naïve hESCs can differentiate to extra-embryonic lineage, and demonstrate a new way of modeling human trophoblast specification and placental methylome establishment.
2020-06-16 | GSE150168 | GEO
Project description:Naïve human embryonic stem cells can give rise to cells with trophoblast-like transcriptome and methylome
| PRJNA638347 | ENA
Project description:Naïve human embryonic stem cells can give rise to cells with trophoblast-like transcriptome and methylome [Bisulfite-Seq]
| PRJNA631288 | ENA
Project description:Naïve human embryonic stem cells can give rise to cells with trophoblast-like transcriptome and methylome [RNA-Seq]
| PRJNA638350 | ENA
Project description:Pancreatic endocrine progenitors obtained from human embryonic stem cells (hESCs) represent a promising source to develop cell-based therapies for diabetes. Although endocrine pancreas progenitor cells have been isolated from mouse pancreata on the basis of Ngn3 expression, human endocrine progenitors have not been isolated yet. As substantial differences exist between human and murine pancreas biology, we investigated whether it is possible to isolate pancreatic endocrine progenitors from differentiating hESC cultures by lineage tracing of NGN3. We targeted the 3' end of NGN3 using zinc finger nuclease-mediated homologous recombination to allow selection of NGN3eGFP(+) cells without disrupting the coding sequence of the gene. Isolated NGN3eGFP(+) cells express PDX1, NKX6.1, and chromogranin A and differentiate in vivo toward insulin, glucagon, and somatostatin single hormone-expressing cells but not to ductal or exocrine pancreatic cells or other endodermal, mesodermal, or ectodermal lineages. This confirms that NGN3(+) cells represent pancreatic endocrine progenitors in humans. In addition, this hESC reporter line constitutes a unique tool that may aid in gaining insight into the developmental mechanisms underlying fate choices in human pancreas and in developing cell-based therapies.
| S-EPMC3973709 | biostudies-literature
Project description:Repair of bone fracture requires recruitment and proliferation of stem cells with the capacity to differentiate to functional osteoblasts. Given the close association of bone and bone marrow (BM), it has been suggested that BM may serve as a source of these progenitors. To test the ability of hematopoietic stem cells (HSCs) to give rise to osteo-chondrogenic cells, we used a single HSC transplantation paradigm in uninjured bone and in conjunction with a tibial fracture model. Mice were lethally irradiated and transplanted with a clonal population of cells derived from a single enhanced green fluorescent protein positive (eGFP+) HSC. Analysis of paraffin sections from these animals showed the presence of eGFP+ osteocytes and hypertrophic chondrocytes. To determine the contribution of HSC-derived cells to fracture repair, non-stabilized tibial fracture was created. Paraffin sections were examined at 7 days, 2 weeks and 2 months after fracture and eGFP+ hypertrophic chondrocytes, osteoblasts and osteocytes were identified at the callus site. These cells stained positive for Runx-2 or osteocalcin and also stained for eGFP demonstrating their origin from the HSC. Together, these findings strongly support the concept that HSCs generate bone cells and suggest therapeutic potentials of HSCs in fracture repair.
| S-EPMC3521579 | biostudies-literature
Project description:UnlabelledBACKGROUND& AIMS: Embryonic biliary precursor cells form a periportal sheet called the ductal plate, which is progressively remodeled to generate intrahepatic bile ducts. A limited number of ductal plate cells participate in duct formation; those not involved in duct development are believed to involute by apoptosis. Moreover, cells that express the SRY-related HMG box transcription factor 9 (SOX9), which include the embryonic ductal plate cells, were proposed to continuously supply the liver with hepatic cells. We investigated the role of the ductal plate in hepatic morphogenesis.MethodsApoptosis and proliferation were investigated by immunostaining of mouse and human fetal liver tissue. The postnatal progeny of SOX9-expressing ductal plate cells was analyzed after genetic labeling, at the ductal plate stage, by Cre-mediated recombination of a ROSA26RYFP reporter allele. Inducible Cre expression was induced by SOX9 regulatory regions, inserted in a bacterial artificial chromosome. Livers were studied from mice under normal conditions and during diet-induced regeneration.ResultsDuctal plate cells did not undergo apoptosis and showed limited proliferation. They generated cholangiocytes lining interlobular bile ducts, bile ductules, and canals of Hering, as well as periportal hepatocytes. Oval cells that appeared during regeneration also derived from the ductal plate. We did not find that liver homeostasis required a continuous supply of cells from SOX9-expressing progenitors.ConclusionsThe ductal plate gives rise to cholangiocytes lining the intrahepatic bile ducts, including its most proximal segments. It also generates periportal hepatocytes and adult hepatic progenitor cells.
| S-EPMC3494970 | biostudies-literature
Project description:The human embryo is not a feasible experimental system for the detailed study of implantation and early placentation, so surrogate systems have been sought for investigating the determination of the trophectoderm lineage, its differentiation into trophoblasts of the early implantation site, and subsequently the morphogenesis of the definitive placenta. An alternative to the use of embryos for studying early placental development was revealed by work with human embryonic stem cells (hESC), demonstrating BMP2/4-stimulated trophoblast differentiation, and spontaneous formation from embryoid bodies (EBs). These cells display a trophoblastic transcriptome, as well as a placental protein and steroid hormone secretory profile, and invasive and chemotactic behavior resembling human placental trophoblasts. With EB-derived trophoblasts, two-dimensional and three-dimensional paradigms and other modifications of the culture environment, including extracellular matrix and aggregation with placental fibroblasts, impact on trophoblast differentiation. Recent studies have questioned the identity of the trophoblasts directed by BMP treatment of hESC, and careful attention to culture conditions is needed to interpret different results among research groups. Although the precise placental counterpart of the hESC-derived trophoblast remains unclear, hESC-derived trophoblasts remain an intriguing platform for modeling early implantation.
| S-EPMC3586288 | biostudies-literature