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Lavoue, V.

Publications and source records attributed to Lavoue, V..

2 recordsLinked to original sources

Single-cell transcriptome landscape of developing fetal gonads defines somatic cell lineage specification in humans

Gonad development is an exciting model to study cell fate commitment. However, the specification and differentiation of somatic cell lineages within the testis and the ovary are incompletely characterized, especially in humans. In fact, a better understanding of sex determination first requires the identification of all the cell types involved and of their dynamic expression programs. Here we present a comprehensive analysis of approximately 128,000 single cells collected from 33 fetal testes and ovaries between 5 and 12 postconceptional weeks. In particular, a focused analysis of somatic cells allowed us to identify a common population of bipotential progenitors derived from the coelomic epithelium of both male and female gonads and capable of committing to either a steroidogenic or a supporting fate. Moreover, we have shown that early supporting cells, prior to further differentiation into Sertoli or granulosa cells, also give rise to the rete testis/ovarii lineage. Finally, we found that the ovary retains the capacity to feed the supporting cell pool for an extended period of time, directly from the surface epithelial cells and, bypassing the bipotential progenitor step. Altogether, our results provide an unprecedented revisiting of the human gonadal sex determination process.

developmental biology↗

Tumor expressed CD95 causes suppression of anti-tumor activity of NK cells in a model of triple negative breast cancer

The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. Stimulation by its cognate ligand CD95L on many cancer cells increases their growth, motility, ability to invade and/or their cancer stemness. Using genetically engineered mouse models of ovarian and liver cancer, we previously reported that deletion of CD95 in the tumor cells strongly reduced their ability to grow in vivo [1, 2]. Using a combination of immune-deficient and immune-competent mouse models, we now establish that loss of CD95 in metastatic triple negative breast cancer cells prevents tumor growth by modulating the immune landscape. CD95 deficient but not wild-type tumors barely grow in an immune-competent environment and show an increase in immune infiltrates into the tumor. This growth reduction is caused by NK cells and does not involve CD8+ T cells. On the other hand, in immune compromised mice CD95 k.o. cells are not growth inhibited, but they fail to form metastases. In summary, we demonstrate that in addition to its tumor and metastasis promoting activities, CD95 expression by tumor cells can exert immune suppressive activities providing a new target for immune therapy.

cancer biology↗