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Spermatogonial stem cells and progenitors are refractory to reprogramming to pluripotency by the transcription factors Oct3/4, c-Myc, Sox2 and Klf4.

Sébastien Corbineau 1, 2 Bruno Lassalle 2, 1 Maelle Givelet 3, 2, 1 Inès Souissi-Sarahoui 4, 1 Virginie Firlej 2, 1 Paul Romeo 2, 1 Isabelle Allemand 5, 1 Lydia Riou 2, 1 Pierre Fouchet 2, 1, *
* Corresponding author
2 Equipe - U967 INSERM - Réparation et Transcription dans les cellules Souches
SCSR (U_967) - Stabilité génétique, Cellules Souches et Radiations
4 Equipe - U967 INSERM - RadioPathologie - LRP
SCSR (U_967) - Stabilité génétique, Cellules Souches et Radiations
5 Equipe - U967 INSERM - Gamétogénèse Apoptose et Génotoxicité - LGAG
SCSR (U_967) - Stabilité génétique, Cellules Souches et Radiations
Abstract : The male germinal lineage, which is defined as unipotent, produces sperm through spermatogenesis. However, embryonic primordial germ cells and postnatal spermatogonial stem cells (SSCs) can change their fate and convert to pluripotency in culture when they are not controlled by the testicular microenvironment. The mechanisms underlying these reprogramming processes are poorly understood. Testicular germ cell tumors, including teratoma, share some molecular characteristics with pluripotent cells, suggesting that cancer could result from an abnormal differentiation of primordial germ cells or from an abnormal conversion of SSCs to pluripotency in the testis. Here, we investigated whether the somatic reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc (OSKM) could play a role in SSCs reprogramming and induce pluripotency using a doxycycline-inducible transgenic Col1a1-4F2A-OSKM mouse model. We showed that, in contrast to somatic cells, SSCs from adult mice are resistant to this reprogramming strategy, even in combination with small molecules, hypoxia, or p53 deficiency, which were previously described to favour the conversion of somatic cells to pluripotency. This finding suggests that adult SSCs have developed specific mechanisms to repress reprogramming by OSKM factors, contributing to circumvent testicular cancer initiation events.
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Submitted on : Thursday, March 30, 2017 - 4:13:11 PM
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Sébastien Corbineau, Bruno Lassalle, Maelle Givelet, Inès Souissi-Sarahoui, Virginie Firlej, et al.. Spermatogonial stem cells and progenitors are refractory to reprogramming to pluripotency by the transcription factors Oct3/4, c-Myc, Sox2 and Klf4.. Oncotarget, Impact journals, 2017, 8 (6), pp.10050-10063. ⟨10.18632/oncotarget.14327⟩. ⟨inserm-01498799⟩

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