Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line

Campolo, Federica; Gori, Manuele; Favaro, Rebecca; Nicolis, Silvia K.; Pellegrini, Manuela; Botti, Flavia; Rossi, Pellegrino; Jannini, Emmanuele A.; Dolci, Susanna

doi:10.1002/stem.1392

Cited by 118 publications

(118 citation statements)

References 59 publications

(90 reference statements)

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…Embryos lacking Sox2 in PGCs showed a dramatic decrease of germ cell numbers at the time of their specification. At later stages, we found that SOX2 is strictly required for PGC proliferation (Campolo et al, 2013). We have also found that SOX2 stimulates Kit expression in PGCs and binds to discrete transcriptional regulatory sequences of this gene, which is known to be essential for PGCs survival and proliferation.…”

Section: Transcription Factors Controlling Kit Expression In the Germmentioning

confidence: 58%

“…Interestingly, ChIP analysis showed that these regulatory regions are present within the Kit first intron, which, as stated above, is essential for Kit expression in PGCs. On the contrary Sox2 conditional deletion in meiotic oocytes does not impair postnatal oogenesis and early embryogenesis, indicating that it is not essential for oocyte maturation nor for zygotic development, and inferring that SOX2 is not involved in the regaining of Kit expression during postnatal oogenesis (Campolo et al, 2013).…”

Section: Transcription Factors Controlling Kit Expression In the Germmentioning

confidence: 92%

“…We recently focused our attention on the possible involvement of the pluripotency-conferring gene Sox2 (SRY-related HMG box 2). Besides being on of the key transcription factors required for embryonic stem cell pluripotency and formation of induced pluripotent stem cells, SOX2 is expressed in mouse PGCs and postnatal oocytes (Avilion et al, 2003;Western et al, 2005, Campolo et al, 2013, but the role played by this transcription factor during germ cell development and early embryogenesis was unknown. Since Sox2 ablation causes early embryonic lethality shortly after blastocyst implantation, we generated mice bearing Sox2-conditional deletion in germ cells at different stages of their development through the Cre/loxP recombination system.…”

Section: Transcription Factors Controlling Kit Expression In the Germmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptional control of KIT gene expression during germ cell development

Rossi¹

2013

Int. J. Dev. Biol.

Self Cite

View full text Add to dashboard Cite

The characterization of the mechanisms that regulate KIT expression in germ cells at different times of their development is important not only in the field of reproduction, but also for a better understanding of the biology of testicular germ cell tumors (TGCTs). Indeed this tyrosine kinase receptor, besides being essential for the survival and proliferation of primordial germ cells (PGCs) and for postnatal spermatogenesis and oogenesis, is also frequently overexpressed or constitutively active due to activating mutations in carcinoma in situ of the testis and in seminomas. In this review, I will summarize available data about the transcriptional mechanisms involved in the control of Kit expression in the germline. Variable mechanisms, involving different germ cell-specific transcription factors, are operating in the various developmental stages: SOX2 and SOHLH1/2 act as direct positive regulators in PGCs and in postnatal spermatogonia, respectively, whereas PLZF suppresses KIT expression in spermatogonial stem cells. DMRT1, acting through indirect mechanisms, suppresses KIT transcription in fetal gonocytes, while activating it in differentiating spermatogonia.

show abstract

Section: Transcription Factors Controlling Kit Expression In the Germmentioning

confidence: 58%

Section: Transcription Factors Controlling Kit Expression In the Germmentioning

confidence: 92%

Section: Transcription Factors Controlling Kit Expression In the Germmentioning

confidence: 99%

See 1 more Smart Citation

Transcriptional control of KIT gene expression during germ cell development

Rossi¹

2013

Int. J. Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Notably, PGCs show dormant totipotency, although PGCs are monopotential cells for the generation of gametes. Nonetheless, PGCs and PSCs remain closely related: both cell types share the expression of several pluripotency-associated transcription factors (9)(10)(11)(12), and PGCs are easily reprogrammed into naïve PSCs, designated embryonic germ cells (EGCs), in culture (13,14). Therefore, the intrinsic mechanisms that control the distinct developmental potential of these two cell types are of great interest.…”

mentioning

confidence: 99%

Distinct requirements for energy metabolism in mouse primordial germ cells and their reprogramming to embryonic germ cells

Hayashi

Otsuka

Ebina

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Primordial germ cells (PGCs), undifferentiated embryonic germ cells, are the only cells that have the ability to become gametes and to reacquire totipotency upon fertilization. It is generally understood that the development of PGCs proceeds through the expression of germ cell-specific transcription factors and characteristic epigenomic changes. However, little is known about the properties of PGCs at the metabolite and protein levels, which are directly responsible for the control of cell function. Here, we report the distinct energy metabolism of PGCs compared with that of embryonic stem cells. Specifically, we observed remarkably enhanced oxidative phosphorylation (OXPHOS) and decreased glycolysis in embryonic day 13.5 (E13.5) PGCs, a pattern that was gradually established during PGC differentiation. We also demonstrate that glycolysis and OXPHOS are important for the control of PGC reprogramming and specification of pluripotent stem cells (PSCs) into PGCs in culture. Our findings about the unique metabolic property of PGCs provide insights into our understanding of the importance of distinct facets of energy metabolism for switching PGC and PSC status.primordial germ cell | metabolome | proteome | glycolysis | oxidative phosphorylation I n mouse, germ cells first develop as primordial germ cells (PGCs) from a subset of cells in late epiblasts consisting of primed pluripotent stem cells (PSCs) that differentiate from naïve PSCs, designated primitive ectoderm or early epiblast, at around embryonic day 7.25 (E7.25) in the extraembryonic mesoderm (1). Several cytokines (2) and transcription factors (3-5) have critical roles in the emergence of PGCs. Following their initial appearance, PGCs migrate and colonize the genital ridges at ∼E10.5, subsequently exhibiting sexual differentiation at ∼E11.5. After their initial development, PGCs undergo characteristic epigenetic reprogramming, including the global reduction of histone H3 lysine 9 dimethylation (H3K9me2) and DNA methylation (6-8). As a result of the dynamic changes in gene regulation and epigenetic states that occur in the course of PGC differentiation, PGCs have developmental potential distinct from that of PSCs. Notably, PGCs show dormant totipotency, although PGCs are monopotential cells for the generation of gametes. Nonetheless, PGCs and PSCs remain closely related: both cell types share the expression of several pluripotency-associated transcription factors (9-12), and PGCs are easily reprogrammed into naïve PSCs, designated embryonic germ cells (EGCs), in culture (13,14). Therefore, the intrinsic mechanisms that control the distinct developmental potential of these two cell types are of great interest.Recent studies have focused primarily on the transcriptome and epigenome to explain the functional difference between PSCs and PGCs. However, the differences in metabolites and proteins in these cells, which may be closely linked to their distinct developmental potential, have not been examined. Recently, exhaustive analyses of metabolites, especially re...

show abstract

“…Sox2 is a transcription factor functionally important for normal stem cells, including pluripotent and tissue-specific stem cell types (8)(9)(10)(11)(12). In the nervous system, Sox2 is active in NSCs and progenitors of the embryo and adult (8,12).…”

Section: Introductionmentioning

confidence: 99%

Sox2 Is Required to Maintain Cancer Stem Cells in a Mouse Model of High-Grade Oligodendroglioma

et al. 2014

Self Cite

View full text Add to dashboard Cite

The stem cell-determining transcription factor Sox2 is required for the maintenance of normal neural stem cells. In this study, we investigated the requirement for Sox2 in neural cancer stem-like cells using a conditional genetic deletion mutant in a mouse model of platelet-derived growth factor-induced malignant oligodendroglioma. Transplanting wild-type oligodendroglioma cells into the brain generated lethal tumors, but mice transplanted with Sox2-deleted cells remained free of tumors. Loss of the tumor-initiating ability of Sox2-deleted cells was reversed by lentiviral-mediated expression of Sox2. In cell culture, Sox2-deleted tumor cells were highly sensitive to differentiation stimuli, displaying impaired proliferation, increased cell death, and aberrant differentiation. Gene expression analysis revealed an early transcriptional response to Sox2 loss. The observed requirement of oligodendroglioma stem cells for Sox2 suggested its relevance as a target for therapy. In support of this possibility, an immunotherapeutic approach based on immunization of mice with SOX2 peptides delayed tumor development and prolonged survival. Taken together, our results showed that Sox2 is essential for tumor initiation by mouse oligodendroglioma cells, and they illustrated a Sox2-directed strategy of immunotherapy to eradicate tumor-initiating cells. Cancer Res; 74(6); 1833-44. Ó2014 AACR.

show abstract

Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line

Cited by 118 publications

References 59 publications

Transcriptional control of KIT gene expression during germ cell development

Transcriptional control of KIT gene expression during germ cell development

Distinct requirements for energy metabolism in mouse primordial germ cells and their reprogramming to embryonic germ cells

Sox2 Is Required to Maintain Cancer Stem Cells in a Mouse Model of High-Grade Oligodendroglioma

Contact Info

Product

Resources

About