Supporting-like cells are an alternative gonadal steroidogenic lineage that is conserved in amniotes
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ABSTRACT:
ORGANISM(S): Oryctolagus cuniculus
PROVIDER: GSE331375 | GEO | 2026/06/30
REPOSITORIES: GEO
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Project description:Testicular fetal Leydig cells are specialized for androgen production during embryogenesis. Testosterone is essential for regulating sex differentiation, spermatogenesis, and fertility. Deficiencies in Leydig cell differentiation can lead to various disorders of sex development and male reproductive conditions, such as ambiguous genitalia, hypospadias, cryptorchidism, and infertility. Understanding the differentiation of fetal Leydig cells is essential for comprehending male sexual differentiation, reproductive health, and fertility. Fetal Leydig cells originate from proliferating progenitor cells in the gonadal interstitium, marked by genes like Arx, Pdgfra, Tcf21, Wnt5a, and Nr2f2. However, the precise mechanisms governing the transition from interstitial cells to Leydig cells remain elusive. Through integrated approaches involving animal models and multiomics, we have demonstrated that fetal Leydig cells originate from a Nr2f2 positive non-steroidogenic interstitial cell population. NR2F2 promotes progenitor cell fate while suppressing Leydig cell differentiation. Moreover, embryonic deletion of Nr2f2 in mouse testes resulted in disorders of sex development, including reduced testicular size, Leydig cell hypoplasia, cryptorchidism, and hypospadias. Collectively, our findings highlight the critical role of Nr2f2 in orchestrating the transition from interstitial cells to Leydig cells during testicular development.
2025-03-24 | GSE275901 | GEO
Project description:Testicular fetal Leydig cells are specialized for androgen production during embryogenesis. Testosterone is essential for regulating sex differentiation, spermatogenesis, and fertility. Deficiencies in Leydig cell differentiation can lead to various disorders of sex development and male reproductive conditions, such as ambiguous genitalia, hypospadias, cryptorchidism, and infertility. Understanding the differentiation of fetal Leydig cells is essential for comprehending male sexual differentiation, reproductive health, and fertility. Fetal Leydig cells originate from proliferating progenitor cells in the gonadal interstitium, marked by genes like Arx, Pdgfra, Tcf21, Wnt5a, and Nr2f2 (COUP-TFII). However, the precise mechanisms governing the transition from interstitial cells to Leydig cells remain elusive. Through integrated approaches involving animal models and multiomics, we have demonstrated that fetal Leydig cells originate from a COUP-TFII positive non-steroidogenic interstitial cell population. COUP-TFII promotes progenitor cell fate while suppressing Leydig cell differentiation. Moreover, embryonic deletion of COUP-TFII in mouse testes resulted in disorders of sex development, including reduced testicular size, Leydig cell hypoplasia, cryptorchidism, and hypospadias. Collectively, our findings highlight the critical role of COUP-TFII in orchestrating the transition from interstitial cells to Leydig cells during testicular development.
2025-03-24 | GSE275900 | GEO
Project description:Supporting-like cells are an alternative gonadal steroidogenic lineage that is conserved in amniotes
| PRJNA1467978 | ENA
Project description:In the present study, microarray analysis was performed on RNA isolated from purified SLCs, PLCs, ILCs, ALCs and bone stem cells, using Affymetrix Rat Genome RAE230 2.0 arrays which monitor ~30,000 transcripts from over ~28,000 well-substantiated genes. The focus is on the differences and similarities between SLCs and bone stem cells, and between SLCs and PLCs, ILCs and ALCs 3-4 replicas of leydig cells from different developmental stages were collected and analyzed
2011-12-28 | E-GEOD-26703 | biostudies-arrayexpress
Project description:Steroid hormones regulate essential physiological processes and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by LH via its receptor leading to increased cAMP production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Leydig cell steroidogenesis then passively decreases following the rapid degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutive steroidogenic cell line R2C. Our data identify AMPK as an active repressor of steroid hormone biosynthesis in steroidogenic cells that is essential to preserve cellular energy and prevent excess steroid production. Steroid hormones regulate essential physiological processes and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by LH via its receptor leading to increased cAMP production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Leydig cell steroidogenesis then passively decreases following the rapid degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutive steroidogenic cell line R2C. Our data identify AMPK as an active repressor of steroid hormone biosynthesis in steroidogenic cells that is essential to preserve cellular energy and prevent excess steroid production. MA-10 Leydig cells were treated with either DMSO (control), 10 uM forskolin or forskolin+Aicar (1 mM) for 1.5 h before total RNA extraction
2014-08-19 | E-GEOD-50118 | biostudies-arrayexpress
Project description:As a unique population of testicular mesenchymal stromal cells, stem Leydig cells (SLCs) have shown great promise in the treatment of male hypogonadism. The therapeutic functions of MSCs are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs have not been fully studied. Here, we found that transplanted SLCs restored testicular immunological homeostasis via damage signal-triggered transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated mitochondrial transfer to macrophages. Specifically, the results showed that SLCs transplantation restored male fertility and testosterone production in an ischemia‒reperfusion injury-induced acute inflammation model. This was achieved mainly via a mechanism involving the prevention of inflammatory cascades but not the differentiation to Leydig cells (LCs), the main testosterone-producing cells. Furthermore, we identified that ROS released from activated macrophages, which are the primary testicular immunocytes, induced nanotube-mediated mitochondrial transfer from SLCs to macrophages via TRPM7. Notably, TRPM7 knockdown by interfering RNA in transplanted SLCs compromised the therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. Collectively, SLC rescued testicular damage in testicular ischemia‒reperfusion mouse models, and the damage signal activated TRPM7 signaling and induced mitochondrial transfer from SLCs to macrophages, playing important roles in the repair of SLCs. These findings provide insight into the clinical translation of SLCs and suggest that strategies targeting mitochondrial transfer may be effective treatments for patients with male hypogonadism related to immune disorders.
2024-02-01 | GSE254881 | GEO
Project description:To achieve single-cell characterization of the adrenal cortex transcriptome, we selectively labeled the steroidogenic adrenocortical cells using a transgenic Cre-LoxP approach. We combined Sf1-Crehigh mice with Rosa26mTmG animals to obtain mice expressing fluorescent reporter proteins at the cell membrane (mTmG) of cells that express or have expressed the transcription factor SF-1 (Steroidogenic Factor 1, also AdBP4, encoded by NR5A1). We prepared a single-cell suspension by combining mechanic and enzymatic dissociation at low temperatures to preserve the viability of steroid cells and their transcriptional states. Fluorescence-activated cell sorting (FACS) was then used to isolate GFP-positive cells representing the steroidogenic lineage. GFP-positive cells include the progenitor populations as well as differentiated cells (zona glomerulosa and zona fasciculata cells).
2025-12-01 | GSE291343 | GEO
Project description:Gonad somatic cells acquire sex-specific fates during sex determination. In XX gonad, a subset of somatic cells expresses Foxl2 after sex determination which are considered as the progenitor of granulosa cells. However, whether these cells also contribute to other cell type at later developmental stage is unknown. In the present study, the cell fate of Foxl2-expressing cells in fetal ovaries was analyzed by lineage tracing and signal-cell transcriptomics. We found that Foxl2-expressing cells gave rise to three cell types at later developmental stage, including granulosa cells, theca-interstitial cells, and stromal cells. Series single-cell RNA sequencing revealed that Foxl2-positive cells were divided into two clusters at P0. One group further differentiated into granulosa cells and theca cells at P14. Another group was classified as stromal cell lineage, then a small portion of them further differentiated into 3β-HSD-positive interstitial cells. We also found that interstitial cells were CYP17a1-positive, whereas theca cells did express this gene. Our data provide an important resource, at single-cell resolution, for better understanding somatic cell differentiation in ovary development.
2022-11-22 | GSE163879 | GEO
Project description:Steroidogenic acute regulatory protein (Star) facilitates cholesterol transfer into the inner mitochondrial membrane in the acute and regulated production of steroid hormones. Mice lacking Star (Star-/-) share the phenotypes with patients with congenital lipoid adrenal hyperplasia such as compromised production of steroid hormones and florid accumulation of cholesterol esters in adrenal glands and gonads. To define specific patterns of molecular changes with disruption of Star, we performed a transcriptome analysis of steroidogenic cells in adrenal glands. We harvested adrenal glands at E17.5 or 18.5 from seven wild-type (Star+/+) mice or four Star-/- mice having the transgene targeting enhanced green fluorescent protein (eGFP) under the control of regulatory sequences of mouse Star gene. Steroidogenic cells were selectively isolated by fluorescent-activated cell sorting. The gene expression profile of the fluorescence-positive cells was obtained with Agilent Whole Mouse Genome Microarray and was confirmed by quantitative real-time PCR. We identified 961 and 622 genes that were significantly up-regulated and down-regulated, respectively, in Star-/- mice compared with Star+/+ mice (fold difference ≥2, p value of Student t test <0.05, and Benjamini-Hochberg false discovery rate of multiple comparison test <0.2). In Star-/- mice, expression levels of genes involved in cholesterol mobilization and efflux or immune response as antigen presenting cells were significantly increased, and transition from fetal to adult adrenocortical cells were significantly decreased, whereas those of genes related to steroid hormone biosynthesis or cholesterol biosynthesis and influx were not significantly changed. The trancriptome analysis revealed hitherto undescribed characteristic changes in adrenocortical cells and expanded our understanding of the pathophysiology of the steroidogenic cells with disruption of Star. Gene expression profiles of isolated adrenal steroidogenic cells were compared between seven wild-type mice and four knockout mice lacking steroidogenic acute regulatory protein at E17.5-18.5.
2011-08-13 | E-GEOD-31328 | biostudies-arrayexpress
Project description:we report that fibroblasts can be efficiently and directly reprogrammed into Leydig-like cells by exposing to a combination of small molecules, Forskolin, 20α-hydroxycholesterol, luteinizing hormone (LH), and SB431542. The chemical compounds induced Leydig-like cells (CiLCs) expressed steroidogenic genes, had a global gene expression profile similar to that of Leydig cell, and acquired androgen synthesis capabilities.
2020-02-26 | GSE145797 | GEO