Spontaneous generation of germline characteristics in mouse fibrosarcoma cells

Ma, Zhan; Hu, Yao; Jiang, Guoying; Hou, Jun; Liu, Ruilai; Lu, Yuan

doi:10.1038/srep00743

Cited by 15 publications

(13 citation statements)

References 32 publications

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“…Second, ectopic expression of germ cell genes in Drosophila drives brain tumor growth 7 . Third, our previous studies showed that germ cell-like cells may exist in cultured cancer cells 8 , 9 and abnormal gametogenesis could be activated by chemical carcinogen 10 . However, no genetic mouse tumor models are utilized to identify the occurrence of germ cell traits in tumors and their potential roles in oncogenic processes.…”

Section: Introductionmentioning

confidence: 97%

Abnormal gametogenesis induced by p53 deficiency promotes tumor progression and drug resistance

et al. 2018

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The century-old embryonal/gametogenesis hypothesis of tumors could link diverse tumors’ malignant features together likely representing the real “stemness” of tumors. However, the genetic evidence to validate abnormal gametogenesis in tumors remains lacking. Here we show that p53 deficiency elicits abnormal gametogenesis from primordial germ cell-like stage to late oocyte-like stage and subsequent parthenogenetic activation. The similar upregulation of abnormal gametogenesis by p53 deficiency is observed both in p53−/− mouse model and cultured cancer cells. Notably, germ cell-like cells isolated from distinct tumors from p53−/− mice and cancer cell lines display potent tumorigenicity potential. Abnormal oogenesis induced by p53 deficiency and then spontaneous parthenogenetic activation endow tumors with imitated embryonic development, life cycle, and therapeutic resistance. Our study establishes the genetic evidence to support embryonal/gametogenesis theory of tumors and reveals a pivotal role of p53 in restricting abnormal gametogenesis that may represent a novel aspect for p53’s tumor suppression.

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Section: Introductionmentioning

confidence: 97%

Abnormal gametogenesis induced by p53 deficiency promotes tumor progression and drug resistance

et al. 2018

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“…Recent work from a range of organisms has revealed that tumors may acquire a more germline-like state. [4][5][6][7][8][9] Moreover, it has been demonstrated that the germline gene expression has the potential to be oncogenic in Drosophila melanogaster 4 and is associated with clinically more aggressive tumors in humans. 8 Janic et al recently demonstrated that l(3)mbt tumors in D. melanogaster ectopically expressed a broad range of germline genes, with up to a quarter of ectopically expressed genes being associated with a known germline function.…”

mentioning

confidence: 99%

Meta‐analysis of expression of l(3)mbt tumor‐associated germline genes supports the model that a soma‐to‐germline transition is a hallmark of human cancers

2013

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Evidence is starting to emerge indicating that tumorigenesis in metazoans involves a soma-to-germline transition, which may contribute to the acquisition of neoplastic characteristics. Here, we have meta-analyzed gene expression profiles of the human orthologs of Drosophila melanogaster germline genes that are ectopically expressed in l(3)mbt brain tumors using gene expression datasets derived from a large cohort of human tumors. We find these germline genes, some of which drive oncogenesis in D. melanogaster, are similarly ectopically activated in a wide range of human cancers. Some of these genes normally have expression restricted to the germline, making them of particular clinical interest. Importantly, these analyses provide additional support to the emerging model that proposes a soma-to-germline transition is a general hallmark of a wide range of human tumors. This has implications for our understanding of human oncogenesis and the development of new therapeutic and biomarker targets with clinical potential.

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Section: Discussionmentioning

confidence: 54%

“…Formation of oocyte-like cells from fetal pig skin ( 27 ) and mouse fibrosarcoma L929 cells ( 28 ) has been reported by other investigators. Although the expression of meiosis gene SCP-3 was shown in oocyte-like cells, the majority of these cells did not enter meiosis properly ( 28 , 29 ). Single-clone analysis of the L929 cells suggested two possible explanations for the spontaneous formation of embryonic-like structures: ( 1 ) the presence of existing germ cells in the pool of fibroblast cells, or ( 2 ) the re-acquisition of germline characteristics due to mutation or epigenetic factors ( 28 ).…”

Section: Discussionmentioning

confidence: 54%

The Role of Microenvironment in Preserving the Potency of Adult Porcine Pulmonary Valve Stem Cells In Vitro

Chalajour

Siyahian

Hanley

2018

IJSC

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Background and ObjectiveThe potency of tissue resident stem cells is regulated primarily by inputs from the local microenvironment. Isolation of stem cells through enzymatic digestion of tissue may affect epigenetic regulation of cell fate and performance. Here we employ a non-enzymatic method to harvest and investigate tissue resident stem cells from the adult porcine pulmonary valve.Methods and ResultsThe presence of c-Kit+ stem cells within the valve tissue was confirmed by immunohistochemistry. An in vitro culture of minced valve leaflets was developed under the standard conditions (37°C with 5% CO2). The viability of the cellular outgrowths was evaluated over the subsequent 12 weeks. Under this culture condition, we identified a population of non-adherent c-Kit+ cells and multiple cellular structures mimicking the phenotype of embryonic stem cells at different stages of development. Formation of multinucleated cells through cell fusion provided an active niche area for homing and interaction of the non-adherent c-Kit+ cells. Expression of pluripotency markers Oct-4 and Nanog was detected in the newly formed multinucleated cells but not in mature colonies. Partial cell fusion was shown by fluorescent live-cell tracking, which confirmed intercellular molecular exchange between donor and recipient cells, resulting in altered cytoplasmic protein expression by the recipient cell.ConclusionsThese results suggest a role for the microenvironment in decrypting the potential of the valve somatic stem cells in vitro. In addition, our data provide evidence for cell fusion, which may play a critical role in reversing somatic cell fate and spontaneous cellular reprogramming.

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Spontaneous generation of germline characteristics in mouse fibrosarcoma cells

Cited by 15 publications

References 32 publications

Abnormal gametogenesis induced by p53 deficiency promotes tumor progression and drug resistance

Abnormal gametogenesis induced by p53 deficiency promotes tumor progression and drug resistance

Meta‐analysis of expression of l(3)mbt tumor‐associated germline genes supports the model that a soma‐to‐germline transition is a hallmark of human cancers

The Role of Microenvironment in Preserving the Potency of Adult Porcine Pulmonary Valve Stem Cells In Vitro

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