Dataset Information

Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features.

ABSTRACT: The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY), and hMSC (46, XY)) into a germ cell-like phenotype in vitro. Induced germ cell-like cells showed a marked switch in their transcriptomic profile and expressed several post-meiotic germ line related markers, showed meiotic progression, evidence of epigenetic reprogramming, and approximately 1% were able to complete meiosis as demonstrated by their haploid status and the expression of several post-meiotic markers. Furthermore, xenotransplantation assays demonstrated that a subset of induced cells properly colonize the spermatogonial niche. Knowledge obtained from this work can be used to create in vitro models to study gamete-related diseases in humans.

SUBMITTER: Medrano JV

PROVIDER: S-EPMC4844986 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features.

Medrano Jose V JV Martínez-Arroyo Ana M AM Míguez Jose M JM Moreno Inmaculada I Martínez Sebastián S Quiñonero Alicia A Díaz-Gimeno Patricia P Marqués-Marí Ana I AI Pellicer Antonio A Remohí Jose J Simón Carlos C

Scientific reports 20160426

The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes P ...[more]

PMID: 27112843

Similar Datasets

Project description:Results from expression arrays identified that whole cultures of i12F-reprogrammed fibroblasts clustered in a defined group and indicated a switch in their genetic expression program, as shown by the significant up-regulation of 342 genes and the down-regulation of 288 genes in treated cells compared to MOCK controls. Manually isolated i12F clumps also clustered in a defined group different to i12F and showed significant up-regulation of 329 genes (193 of them shared with i12F treatment) and down-regulation of 372 genes (225 of them shared with i12F treatment) compared to MOCK controls (Fig. 1B). Functional enrichment analysis of the list of differentially regulated genes in i12F indicated their implication in germ cell-related processes such as “Integrin cell surface interactions” (REACT_13552), “Cell cycle” (REACT_152), “DNA Replication” (REACT_383), “Telomere maintenance (REACT_7970), as well as several Gene Ontology biological processes related to “Positive regulation of MAP kinase activity” (GO:0043406), “ovarian follicle development” (GO:0001541), “positive regulation of tyrosine phosphorylation of STAT protein” (GO:0042531), “Retinoid acid metabolic process” (GO:0042573) and “transforming growth factor beta receptor signaling pathway” (GO:0007179), among others. Interestingly, we observed the significant down-regulation of several genes related to the mitotic cell cycle regulation such as CDC45L, RRM2, CDKL2, CENPM, CENPP, ZWINT, PRKAR2B, PKMYT1, SKA3, ADORA2B, CDCA8, CDC6, BUB1 and LIG1, and the significant up-regulation of genes related to the TGFβ and LIF/STAT3 pathways such as INHBA, IL6, CSF2 and MAFB, and cell attachment to basal layer such as ITGA1, MMP9 and MMP10. On the other hand, we observed a specific significant down-regulation in the CLUMPS of several genes related to chromatin stability such as the linker histone 1 subunits H4B, H4H, H4K, H2AB and H3J, the core histone 2 subunits H2AA4 and H4B, and several somatic lineage determinant factors such as GATA2, NEUROD2 and SOX17. Aditionally we observed a significant up-regulation of extracellular matrix related genes such as ADAM8 and MMP14, and the pathway of LIF/STAT3

Dataset Information

Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features.

Publications

Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets