ArticleStem cell research & therapy2020
Analysis of multi-lineage gene expression dynamics during primordial germ cell induction from human induced pluripotent stem cells.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 51 citations in OpenAlex.
- The balance between NANOG and SOX17 mediated by TET proteins regulates specification of human primordial germ cell fate.Cell & bioscience · 2022Article
- A homozygous PIWIL2 frameshift variant affects the formation and maintenance of human-induced pluripotent stem cell-derived spermatogonial stem cells and causes Sertoli cell-only syndrome.Stem cell research & therapy · 2022Article
- Valproic acid promotes the in vitro differentiation of human pluripotent stem cells into spermatogonial stem cell-like cells.Stem cell research & therapy · 2021Article
- Neonatal Porcine Germ Cells Dedifferentiate and Display Osteogenic and Pluripotency Properties.Cells · 2021Article
- miR-296-5p Inhibits the Secretion of Pulmonary Surfactants in Pulmonary Epithelial Cells via the Downregulation of Wnt7b/BioMed research international · 2021Article
- Dynamics of Transcription Factors in Three Early Phases of Osteogenic, Adipogenic, and Chondrogenic Differentiation Determining the Fate of Bone Marrow Mesenchymal Stem Cells in Rats.Frontiers in cell and developmental biology · 2021Article
- Differential genetic mutations of ectoderm, mesoderm, and endoderm-derived tumors in TCGA database.Cancer cell international · 2020Article
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn mammals, specification of primordial germ cells (PGCs) is established in the early post-implantation embryo. The bone morphogenetic protein (BMP)-SMAD and WNT3-β-catenin signaling initiate the gene regulatory network for PGC specification. The activation of SOX17-BLIMP1 axis is critical for human PGC program. Moreover, EpCAM and INTEGRINα6 were identified as surface markers of human PGC-like cells (PGCLCs) recently. However, the signaling mechanism for PGC specification in non-rodent mammals remains to be clarified.
methodsWe differentiated human induced pluripotent stem cells (hiPSCs) into PGCLCs in vitro in response to Activin A and BMP4. The percentage of EpCAM/INTEGRINα6 double-positive cells (PGCLCs) was analyzed by flow cytometry. The expression of PGC genes was evaluated by qRT-PCR and immunofluorescence. The expression dynamic of multi-lineage genes during the differentiation process was evaluated by qRT-PCR.
resultsUnder the stimulation for PGCLC induction, the embryoids derived from hiPSCs initiated significant upregulation of the early PGC genes (BLIMP1, TFAP2C, and NANOS3), but maintained low or no levels of DPPA3 and late PGC genes (DAZL and DDX4). The percentage of EpCAM/INTEGRINα6 double-positive PGCLCs reached the highest at day 6 of induction. After pre-induction, the incipient mesoderm-like cells (iMeLCs) upregulated most of the mesoderm genes (EOMES, T, MSXI, RUNX2, and MIXL1). The differentiating embryoids showed high levels of key pluripotency genes, OCT4 and NANOG, but became negative for SOX2. In contrast to iMeLCs, the differentiating embryoids downregulated mesoderm genes RUNX2 and EOMES, and ectoderm gene PAX6, but increased the expression of endoderm gene SOX17.
conclusionsDuring PGCLC induction process in vitro, the differentiating embryoids not only activated the PGC-related genes, but also displayed complex regulation of pluripotency genes and multi-lineage genes. These results would be meaningful for future research investigating the regulation of human early germ line development.
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