Single‐cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination

Mayère, Chloé; Neirijnck, Yasmine; Sararols, Pauline; Rands, Chris M.; Stévant, Isabelle; Kühne, Françoise; Chassot, Anne-Amandine; Chaboissier, Marie-Christine; Dermitzakis, Emmanouil T.; Nef, Serge

doi:10.1096/fj.202002420r

Cited by 50 publications

(61 citation statements)

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“…We found that the expression profiles of migrating PGCs (at E2.5) resemble those of colonized PGCs (at E6 in males and at E6–E8 in females). In mice, it is known that the transcriptomes of XX and XY cells overlap at the early developmental stage, whereas sex-specific branches are formed in the differentiated cells at the late stages [100] . However, in this study, chickens showed differences in transcriptome levels between mS1 and fS1 (early-stage germ cells).…”

Section: Discussionmentioning

confidence: 99%

Dissecting chicken germ cell dynamics by combining a germ cell tracing transgenic chicken model with single-cell RNA sequencing

Rengaraj

Gon

Lee

et al. 2022

Computational and Structural Biotechnology Journal

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Section: Discussionmentioning

confidence: 99%

Dissecting chicken germ cell dynamics by combining a germ cell tracing transgenic chicken model with single-cell RNA sequencing

Rengaraj

Gon

Lee

et al. 2022

Computational and Structural Biotechnology Journal

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“…Genetic sexing was performed by PCR, as described previously ( 61 ). Urogenital ridges including both the gonads and mesonephros (E10.5, E11.5) from both sexes, and testes or ovaries (E12.5-E16.5), were isolated at each time point and enzymatically dissociated as described previously ( 62 ). Approximately 5000 single cells were loaded on a 10x Chromium instrument and scRNA-seq libraries were prepared using the 10X Genomics Chromium Controller and Chromium Single Cell 3’ Library & Gel Bead Kit V2, as per the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Section: Sample Collection and Single Cell Transcript Profilingmentioning

confidence: 99%

Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad

Mayère

Regard

Perea-Gómez

et al. 2021

Preprint

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Gonadal sex determination represents a unique model for studying cell fate decisions. However, a complete understanding of the different cell lineages forming the developing testis and ovary remains elusive. Here, we investigated the origin, specification and subsequent sex-specific differentiation of a previously uncharacterized population of supporting-like cells (SLC) in the developing mouse gonads. The SLC lineage is closely related to the coelomic epithelium and specified as early as E10.5, making it the first somatic lineage to be specified in the bipotential gonad. SLC progenitors are localized within the genital ridge at the interface with the mesonephros and initially co-express Wnt4 and Sox9. SLCs become sexually dimorphic around E12.5, progressively acquire a Sertoli- or granulosa-like identity and contribute to the formation of the rete testis and rete ovarii. Finally, we found that WNT4 is a crucial regulator of the SLC lineage and is required for the formation of the rete testis.

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“…We can generate high quality early gonadal progenitors and Sertoli-like cells. The system could be refined further to produce other somatic lineages of the gonad, such as Leydig and peritubular myoid cells of the testis or granulosa and theca cells of the ovary, as well as other gonadal lineages that are being identified by single-cell sequencing approaches (Mayere et al, 2021;Stevant et al, 2019;Stevant et al, 2018). Recently, foetal ovarian somatic cell-like cells (FOSLCs) were derived from mESC, using an approach similar to ours.…”

Section: Discussionmentioning

confidence: 99%

In-vitro cellular reprogramming to model gonad development and its disorders

Gonen

Eozénou

Mitter

et al. 2021

Preprint

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During embryonic development, mutually antagonistic signaling cascades determine the fate of the bipotential gonad towards a testicular or ovarian identity. Errors in this process result in human Disorders of Sex Development (DSDs), where there is discordance between chromosomal, gonadal, and anatomical sex. The absence of an appropriate, accessible in-vitro system is a major obstacle in understanding mechanisms of sex-determination/DSDs. Here, we describe protocols for differentiation of mouse and human pluripotent cells towards gonadal progenitors. Transcriptomic analysis reveals that the in-vitro-derived murine gonadal cells are equivalent to E11.5 in-vivo progenitors. Using similar conditions, Sertoli-like cells derived from 46,XY human induced pluripotent stem cells (hiPSCs) exhibit sustained expression of testis-specific genes, secrete AMH, migrate and form tubular structures. The cells derived from a 46,XY DSD female hiPSCs, carrying a NR5A1 variant, show aberrant gene expression and absence of tubule formation. CRISPR/Cas9-mediated correction of the variant rescued the phenotype. This is a robust tool to understand mechanisms of sex-determination and model DSDs.

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Single‐cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 50 publications

References 103 publications

Dissecting chicken germ cell dynamics by combining a germ cell tracing transgenic chicken model with single-cell RNA sequencing

Dissecting chicken germ cell dynamics by combining a germ cell tracing transgenic chicken model with single-cell RNA sequencing

Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad

In-vitro cellular reprogramming to model gonad development and its disorders

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