ArticleOncotarget2017
CHIR99021 combined with retinoic acid promotes the differentiation of primordial germ cells from human embryonic stem cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Establishment and longitudinal characterisation of a feeder-free embryonic stem-like cell line (ATES1) derived from blastomeres of the climbing perch, Anabas testudineus.Fish physiology and biochemistry · 2026Article
- Beyond Small Molecules: Orchestrating Cell Fate with Engineered Water-Soluble Membrane Proteins.Biomolecules · 2026Article
- In Vitro Gamete Production in Mammals: Decades of Pioneering Approaches in Germ Cell and Stem Cell Biology Supporting Innovative Discovery and Expansion of Human Reproductive Potential.Molecular reproduction and development · 2025Review
- Generating human primordial germ cell-like cells from pluripotent stem cells: a scoping review ofHuman reproduction open · 2025Review
- Rapid retinoic acid-induced trophoblast cell model from human induced pluripotent stem cells.Scientific reports · 2024Article
- Early Gonadal Development and Sex Determination in Mammal.International journal of molecular sciences · 2022Review
- Translating around the clock: Multi-level regulation of post-transcriptional processes by the circadian clock.Cellular signalling · 2021Review
- GSK3β Interacts With CRMP2 and Notch1 and Controls T-Cell Motility.Frontiers in immunology · 2021Article
- Effects of signaling pathway inhibitors on hematopoietic stem cells.Molecular medicine reports · 2021Article
- GSK‑3 inhibitor CHIR99021 enriches glioma stem‑like cells.Oncology reports · 2020Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primordial germ cells (PGCs) derived from human embryonic stem cells (hESCs) represent as a desirable experimental model as well as a potential strategy for treating male infertility. Here, we developed a simple and feasible method for differentiation of PGCs from hESCs by using CHIR99021 (an inhibitor of glycogen synthase kinase 3) and retinoic acid (RA). We firstly found that the deleted in azoospermia-like (DAZL) protein can be detected in 3 d CHIR99021 plus 9 d retinoic acid treated cultures and 12 d CHIR99021 plus retinoic acid co-treated cultures, but not expressed in single CHIR99021 treated cultures, single retinoic acid treated cultures, as well as 3 d retinoic acid plus 9 d CHIR99021 treated cultures. Next, we showed that several PGCs' markers were expressed in the 12 d CHIR99021 and retinoic acid co-treated cultures or 3 d CHIR99021 plus 9 d retinoic acid treated cultures. Moreover, meiosis was initiated in CHIR99021 and retinoic acid co-treated cultures as evidenced by a significant expression of the punctate synaptonemal complex protein 3 (SCP3). Fluorescent in situ hybridization (FISH) analysis indicated that a small percentage of putative 1N populations were formed. Mechanically, we found that β-catenin relocated into nucleus after the treatment of 3 d CHIR99021 suggesting that Wnt signaling pathway was activated. Furthermore, blockade of Wnt signaling pathway by IWR-1 can reverse CHIR99021 and retinoic acid mediated-effects. Taken together, our results indicate that CHIR99021 combined with retinoic acid can effectively differentiate hESCs into PGCs via activating Wnt signaling pathway.
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