Back to Search
Start Over
Robust In Vitro Induction of Human Germ Cell Fate from Pluripotent Stem Cells.
- Source :
-
Cell stem cell [Cell Stem Cell] 2015 Aug 06; Vol. 17 (2), pp. 178-94. Date of Electronic Publication: 2015 Jul 16. - Publication Year :
- 2015
-
Abstract
- Mechanisms underlying human germ cell development are unclear, partly due to difficulties in studying human embryos and lack of suitable experimental systems. Here, we show that human induced pluripotent stem cells (hiPSCs) differentiate into incipient mesoderm-like cells (iMeLCs), which robustly generate human primordial germ cell-like cells (hPGCLCs) that can be purified using the surface markers EpCAM and INTEGRINα6. The transcriptomes of hPGCLCs and primordial germ cells (PGCs) isolated from non-human primates are similar, and although specification of hPGCLCs and mouse PGCs rely on similar signaling pathways, hPGCLC specification transcriptionally activates germline fate without transiently inducing eminent somatic programs. This includes genes important for naive pluripotency and repression of key epigenetic modifiers, concomitant with epigenetic reprogramming. Accordingly, BLIMP1, which represses somatic programs in mice, activates and stabilizes a germline transcriptional circuit and represses a default neuronal differentiation program. Together, these findings provide a foundation for understanding and reconstituting human germ cell development in vitro.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Base Sequence
Biomarkers metabolism
Cell Differentiation
Epigenesis, Genetic
Genes, Reporter
Gonads cytology
Humans
Macaca fascicularis
Mesoderm cytology
Mice
Molecular Sequence Data
Neurons cytology
Positive Regulatory Domain I-Binding Factor 1
Repressor Proteins metabolism
Signal Transduction
Transcription, Genetic
Cell Lineage
Germ Cells cytology
Germ Cells metabolism
Induced Pluripotent Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1875-9777
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell stem cell
- Publication Type :
- Academic Journal
- Accession number :
- 26189426
- Full Text :
- https://doi.org/10.1016/j.stem.2015.06.014