Biology subjects

Lardenois, A.

Publications and source records attributed to Lardenois, A..

4 recordsLinked to original sources

bioRxiv2026

Rspo1 dependent WNT signaling safeguards ovarian development by suppressing androgen signaling

Embryonic ovarian development requires high levels of WNT/B-catenin signaling yet the molecular basis of this requirement remains unclear. Mutations in the WNT potentiator RSPO1 impair ovarian development in both mouse and human, leading to gonadal masculinization in XX individuals. Here, we show that RSPO1 acts within a restricted developmental window at the onset of ovarian differentiation and that its absence triggers precocious androgen signaling in the developing ovaries. Moreover, androgen receptor inhibition rescues ovarian development in Rspo1 mutant mice. Our findings identify RSPO1/WNT/B-catenin signaling as an essential pathway that suppresses androgen signaling to ensure proper ovarian development in mouse.

developmental biology↗

bioRxiv2023

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↗

bioRxiv2022

Multimodal Mapping of Human Lymphopoiesis Reveals B and T/NK/ILC Lineages are Subjected to Cell-Intrinsic versus Flt3L-Dependent Regulation

The developmental cartography of human lymphopoiesis remains incompletely understood. Here, we establish a multimodal map that extends the current view of lymphoid development. Our results demonstrate that lymphoid specification follows independent direct or stepwise differentiation pathways converging toward the emergence of CD117lo multi-lymphoid progenitors (MLPs) that undergo a proliferation arrest before entering the CD127- (T/NK/ILC) or CD127+ (B) lymphoid pathways. While the emergence of CD127- early lymphoid progenitors is driven by Flt3 signaling, differentiation of their CD127+ counterparts is regulated cell-intrinsically and depends exclusively on the divisional history of their precursors. Single-cell mapping of lymphoid differentiation trajectories reveals that a dissociation between proliferation and differentiation phases allows amplification of the precursor pools prior to the onset of antigen receptor rearrangement. Besides demonstrating that B and T/NK/ILC lineages are subjected to differential cell-autonomous versus Flt3-inducible regulation, our results go a long way to reconciling human and mouse models of lymphoid architecture.

immunology↗

bioRxiv2020

FlexDotPlot: a universal and modular dot plot visualization tool for complex multifaceted data

MotivationDot plots are heatmap-like charts that provide a compact way to simultaneously display two quantitative information by means of dots of different sizes and colours. Despite the popularity of this visualization method, particularly in single-cell RNA-seq studies, existing tools used to make dot plots are limited in terms of functionality and usability. ResultsWe developed FlexDotPlot, an R package for generating dot plots from multifaceted data, including single-cell RNA-seq data. It provides a universal and easy-to-use solution with a high versatility. An interactive R Shiny application is also available allowing non-R users to easily generate dot plots with several tunable parameters. Availability and implementationSource code, detailed manual, and code to reproduce figures are available at https://github.com/Simon-Leonard/FlexDotPlot. A Shiny app is available as a stand-alone application within the package.

bioinformatics↗