Tcf21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA635561 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11862356_1.fastq.gz | Fastqsanger.gz | |||
| SRR11862356_2.fastq.gz | Fastqsanger.gz | |||
| SRR11862357_1.fastq.gz | Fastqsanger.gz | |||
| SRR11862357_2.fastq.gz | Fastqsanger.gz | |||
| SRR11862358_1.fastq.gz | Fastqsanger.gz |
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Project description:Testicular development and function relies on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity decline in aging and disease. Whether the adult testis maintains a reserve progenitor population with repair or regenerative capacity remains uncertain. Here, we characterized a recently identified mouse testis interstitial population expressing the transcription factor Tcf21. We found that Tcf21+ cells are bipotential somatic progenitors present in fetal testis and ovary, maintain adult testis homeostasis during aging, and act as reserve somatic progenitors following injury. In vitro, Tcf21+ cells are multipotent mesenchymal progenitors which form multiple somatic lineages including Leydig and myoid cells. Additionally, Tcf21+ cells resemble resident fibroblast populations reported in other organs having roles in tissue homeostasis, fibrosis, and regeneration. Our findings reveal that the testis, like other organs, maintains multipotent mesenchymal progenitors that can be leveraged in development of future therapies for hypoandrogenism and/or infertility.
2021-05-08 | GSE151337 | GEO
Project description:Testicular development and function rely on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity declines in aging and disease. Whether the adult testis maintains a reserve progenitor population remains uncertain. Here, we characterize a recently identified mouse testis interstitial population expressing the transcription factor Tcf21. We found that TCF21lin cells are bipotential somatic progenitors present in fetal testis and ovary, maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury. In vitro, TCF21lin cells are multipotent mesenchymal progenitors which form multiple somatic lineages including Leydig and myoid cells. Additionally, TCF21+ cells resemble resident fibroblast populations reported in other organs having roles in tissue homeostasis, fibrosis, and regeneration. Our findings reveal that the testis, like other organs, maintains multipotent mesenchymal progenitors that can be potentially leveraged in development of future therapies for hypoandrogenism and/or infertility.
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Project description:The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex-determining factor SRY as the basic-helix-loop-helix (bHLH) transcription factor TCF21. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response element both in vitro and in vivo during male sex determination. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to promote precursor Sertoli cell differentiation. Therefore, SRY acts directly on the Tcf21 promoter to, in part, initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development. We used microarrays to determine genes whose expression was stimulated in rat E13 ovarian cell sub-cultures in the presence of a pCMV-myc-expression plasmid over-expressing the Sry, Tsf21, and/or Tcf12 (Reb-alfa) genes. RNA samples from the control group (untreated E13 rat ovarian cells) are compared to RNA from 4 groups of treated E13 rat ovarian cells: 1) Sry overexpressing, 2) Tcf21 overexpressing, 3) Tcf12 (Reb alfa) overexpressing, and 4) Tcf21 + Tcf12 (Reb-alfa) overexpressing. Untreated E13 testis cell sub-cultures were also analyzed. 3 biological replicates each group.
2011-04-25 | E-GEOD-24666 | biostudies-arrayexpress
Project description:Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Using reporter gene and immunolocalization studies with mouse and human tissues we have found that vascular TCF21 expression in the adult is restricted primarily to adventitial cells associated with coronary arteries and also medial SMC in the proximal aorta of mouse. Genome wide RNA-Seq studies in human coronary artery SMC (HCASMC) with siRNA knockdown found a number of putative TCF21 downstream pathways identified by enrichment of terms related to CAD, including “vascular disease,” “disorder of artery,” and “occlusion of artery” as well as disease-related cellular functions including “cellular movement,” and “cellular growth and proliferation.” In vitro studies in HCASMC demonstrated that TCF21 expression promotes proliferation and migration and inhibits SMC lineage marker expression. Detailed in situ expression studies with reporter gene and lineage tracing revealed that vascular wall cells expressing Tcf21 before disease initiation migrate into vascular lesions of ApoE-/- and Ldlr-/- mice. While Tcf21 lineage traced cells are distributed throughout the early lesions, in mature lesions they contribute to the formation of a subcapsular layer of cells, and others become associated with the fibrous cap. The lineage traced fibrous cap cells activate expression of SMC markers and growth factor receptor genes. Taken together, these data suggest that TCF21 may have a role regulating the differentiation state of SMC precursor cells that migrate into vascular lesions and contribute to the fibrous cap and more broadly, in view of the association of this gene with human CAD, provide evidence that these processes may be a mechanism for CAD risk attributable to the vascular wall.
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Project description:The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex-determining factor SRY as the basic-helix-loop-helix (bHLH) transcription factor TCF21. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response element both in vitro and in vivo during male sex determination. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to promote precursor Sertoli cell differentiation. Therefore, SRY acts directly on the Tcf21 promoter to, in part, initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development.
2011-04-25 | GSE24666 | GEO
Project description:From fish to human, FOXL2 is considered one of the most conserved markers of ovarian granulosa cell identity. To determine if the sole expression of FOXL2 can determine ovarian differentiation, we created a mouse model that allows the conditional expression of FOXL2. Rosa26-CAG-LSL-Foxl2 mice were crossed to Sf1-Cre mice to induce the expression of FOXL2 in the SF1+ somatic cells of the fetal gonads.When FOXL2 was induced in the somatic cells of the undifferentiated testis, the Sertoli cells and consequently the other cell lineages composing the fetal gonads were feminized, resulting in a partial testis-to-ovary sex reversal We created a mouse genetic model that conditionaly express FOXL2 in the somatic cells of the fetal gonads. All embryos used in this study resulted from the crossing between Rosa26-CAG-LSL-Foxl2+/f and Sf1-cre+/Tg mice. XX and XY fetal gonads were collected at embryonic day E14.5. This microarray analysis led to the identification of the genes misregulated upon ectopic induction of FOXL2 in the fetal testis, and showed that FOXL2 expression resulted in feminization of both somatic and germ cells of the fetal gonad.
2019-03-25 | GSE78774 | GEO
Project description:The Piwi-piRNA pathway is well known for its germline function, yet its somatic role remains elusive. We show here that Piwi is required autonomously not only for germline stem cell (GSC) but also for somatic cyst stem cell (CySC) maintenance in the Drosophila testis. Reducing Piwi activity in the testis caused defects in CySC differentiation. Accompanying this, GSC daughters expanded beyond the vicinity of the hub but failed to differentiate further. Moreover, Piwi deficient in nuclear localization caused similar defects in somatic and germ cell differentiation, which was rescued by somatic Piwi expression. To explore the underlying molecular mechanism, we identified Piwi-bound piRNAs that uniquely map to a gene key for gonadal development, Fasciclin 3, and demonstrate that Piwi regulates its expression in somatic cyst cells. Our work reveals the cell-autonomous function of Piwi in both somatic and germline stem cell types, with somatic function possibly via its epigenetic mechanism. Examination of Piwi-piRNAs in fly testis
2015-05-23 | E-GEOD-68997 | biostudies-arrayexpress
Project description:The Piwi-piRNA pathway is well known for its germline function, yet its somatic role remains elusive. We show here that Piwi is required autonomously not only for germline stem cell (GSC) but also for somatic cyst stem cell (CySC) maintenance in the Drosophila testis. Reducing Piwi activity in the testis caused defects in CySC differentiation. Accompanying this, GSC daughters expanded beyond the vicinity of the hub but failed to differentiate further. Moreover, Piwi deficient in nuclear localization caused similar defects in somatic and germ cell differentiation, which was rescued by somatic Piwi expression. To explore the underlying molecular mechanism, we identified Piwi-bound piRNAs that uniquely map to a gene key for gonadal development, Fasciclin 3, and demonstrate that Piwi regulates its expression in somatic cyst cells. Our work reveals the cell-autonomous function of Piwi in both somatic and germline stem cell types, with somatic function possibly via its epigenetic mechanism.
2015-05-23 | GSE68997 | GEO
Project description:In many metazoans, germ cells are separated from somatic lineages early in development and maintain their identity throughout life. Here we show that a Polycomb group (PcG) component, Enhancer of Zeste [E(z)] H3K27me3-specific methyltransferase, maintains germline identity in Drosophila adult testes. We find excessive early-stage somatic gonadal cells in E(z) mutant testes, which originate from both over-proliferative cyst stem cells and germ cells turning on an early-stage somatic cell marker. Using complementary lineage-tracing experiments in E(z) mutant testes, a portion of excessive early-stage somatic gonadal cells are found to derive from early-stage germ cells, including germline stem cells. Interestingly, knocking down E(z) specifically in somatic cells caused this germline-to-soma change, suggesting a non-cell autonomous role of E(z) to antagonize somatic identity in germ cells. Using fly testis specifically expressing E(z) shmiR RNAi in germ cells by nos promoter driven GAL4>UAS system, ChIPseq with H3K27me3 antibody was performed, where H3K27me3 is only detected in somatic cells.
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