Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly

Stem Cells International ◽

10.1155/2016/5096596 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Deepa Bhartiya ◽

Seema Parte ◽

Hiren Patel ◽

Kalpana Sriraman ◽

Kusum Zaveri ◽

...

Keyword(s):

Stem Cells ◽

Primordial Germ Cells ◽

Primordial Follicle ◽

Reproductive Period ◽

Surface Epithelium ◽

Alternative Source ◽

Self Renewal ◽

Premature Failure ◽

Ovary Surface Epithelium

Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers) and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes). These stem cells have the ability to spontaneously differentiate into oocyte-like structuresin vitroand on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility.

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FSH–FSHR3–stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer

Reproduction ◽

10.1530/rep-14-0220 ◽

2015 ◽

Vol 149 (1) ◽

pp. R35-R48 ◽

Cited By ~ 28

Author(s):

Deepa Bhartiya ◽

Jarnail Singh

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Stem Cell ◽

Mapk Pathway ◽

Adult Life ◽

Primordial Follicle ◽

Stem Cell Differentiation ◽

Surface Epithelium ◽

Ovarian Cancer Stem Cells ◽

Ovary Surface Epithelium

Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH–FSHR3–stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH–FSHR3–stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers.

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Chemokine (C-X-C) Ligand 12 Facilitates Trafficking of Donor Spermatogonial Stem Cells

Stem Cells International ◽

10.1155/2016/5796305 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Zhiyv Niu ◽

Shaun M. Goodyear ◽

Mary R. Avarbock ◽

Ralph L. Brinster

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Primordial Germ Cells ◽

Critical Role ◽

Spermatogonial Stem Cells ◽

The Self ◽

Self Renewal ◽

Critical Window ◽

Cxcr4 Signaling

The chemokine (C-X-C) receptor type 4 (CXCR4) is an early marker of primordial germ cells (PGCs) essential for their migration and colonization of the gonads. In spermatogonial stem cells (SSCs), the expression of CXCR4 is promoted by the self-renewal factor, glial cell line-derived neurotrophic factor (GDNF). Here, we demonstrate an important role of CXCR4 during donor mouse SSCs reoccupation of the endogenous niche in recipient testis. Silencing of CXCR4 expression in mouse SSCs dramatically reduced the number of donor stem cell-derived colonies, whereas colony morphology and spermatogenesis were comparable to controls. Inhibition of CXCR4 signaling using a small molecule inhibitor (AMD3100) during the critical window of homing also significantly lowered the efficiency of donor-derived SSCs to establish spermatogenic colonies in recipient mice; however, the self-renewal of SSCs was not affected by exposure to AMD3100. Rather,in vitromigration assays demonstrate the influence of CXCR4-CXCL12 signaling in promoting germ cell migration. Together, these studies suggest that CXCR4-CXCL12 signaling functions to promote homing of SSCs towards the stem cell niche and plays a critical role in reestablishing spermatogenesis.

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Hexachlorobenzene toxicity in the rat ovary: II. Ultrastructure induced by medium (10 mg/kg) dose exposure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012374x ◽

1992 ◽

Vol 50 (1) ◽

pp. 668-669

Author(s):

Amreek Singh ◽

Warren G. Foster ◽

Anna Dykeman ◽

David C. Villeneuve

Keyword(s):

Germ Cells ◽

Primordial Germ Cells ◽

Surface Epithelium ◽

Morphological Parameters ◽

Comprehensive Investigation ◽

Ovary Surface Epithelium ◽

Rat Ovary ◽

High Doses

Hexachlorobenzene (HCB) is a known toxicant that is found in the environment as a by-product during manufacture of certain pesticides. This chlorinated chemical has been isolated from many tissues including ovary. When administered in high doses, HCB causes degeneration of primordial germ cells and ovary surface epithelium in sub-human primates. A purpose of this experiment was to determine a no-effect dose of the chemical on the rat ovary. The study is part of a comprehensive investigation on the effects of the compound on the biochemical, hematological, and morphological parameters in the monkey and rat.

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Faculty Opinions recommendation of Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1677956.1501058 ◽

2010 ◽

Author(s):

Richard Gilbertson

Keyword(s):

Stem Cells ◽

Self Renewal

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Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro

Processes ◽

10.3390/pr9010045 ◽

2020 ◽

Vol 9 (1) ◽

pp. 45

Author(s):

Ghmkin Hassan ◽

Said M. Afify ◽

Shiro Kitano ◽

Akimasa Seno ◽

Hiroko Ishii ◽

...

Keyword(s):

Stem Cells ◽

Cancer Biology ◽

Advanced Technology ◽

Cancer Microenvironment ◽

Critical Factors ◽

Self Renewal ◽

Cell Microenvironment ◽

Biological Phenomena ◽

Biomaterial Scaffolds

Defined by its potential for self-renewal, differentiation and tumorigenicity, cancer stem cells (CSCs) are considered responsible for drug resistance and relapse. To understand the behavior of CSC, the effects of the microenvironment in each tissue are a matter of great concerns for scientists in cancer biology. However, there are many complicated obstacles in the mimicking the microenvironment of CSCs even with current advanced technology. In this context, novel biomaterials have widely been assessed as in vitro platforms for their ability to mimic cancer microenvironment. These efforts should be successful to identify and characterize various CSCs specific in each type of cancer. Therefore, extracellular matrix scaffolds made of biomaterial will modulate the interactions and facilitate the investigation of CSC associated with biological phenomena simplifying the complexity of the microenvironment. In this review, we summarize latest advances in biomaterial scaffolds, which are exploited to mimic CSC microenvironment, and their chemical and biological requirements with discussion. The discussion includes the possible effects on both cells in tumors and microenvironment to propose what the critical factors are in controlling the CSC microenvironment focusing the future investigation. Our insights on their availability in drug screening will also follow the discussion.

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Formative pluripotent stem cells show features of epiblast cells poised for gastrulation

Cell Research ◽

10.1038/s41422-021-00477-x ◽

2021 ◽

Author(s):

Xiaoxiao Wang ◽

Yunlong Xiang ◽

Yang Yu ◽

Ran Wang ◽

Yu Zhang ◽

...

Keyword(s):

Stem Cells ◽

Germ Cells ◽

Pluripotent Stem Cells ◽

Primordial Germ Cells ◽

Embryonic Stem ◽

Large Set ◽

Mouse Escs ◽

Epiblast Stem Cells ◽

Early Gastrula

AbstractThe pluripotency of mammalian early and late epiblast could be recapitulated by naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), respectively. However, these two states of pluripotency may not be sufficient to reflect the full complexity and developmental potency of the epiblast during mammalian early development. Here we report the establishment of self-renewing formative pluripotent stem cells (fPSCs) which manifest features of epiblast cells poised for gastrulation. fPSCs can be established from different mouse ESCs, pre-/early-gastrula epiblasts and induced PSCs. Similar to pre-/early-gastrula epiblasts, fPSCs show the transcriptomic features of formative pluripotency, which are distinct from naïve ESCs and primed EpiSCs. fPSCs show the unique epigenetic states of E6.5 epiblast, including the super-bivalency of a large set of developmental genes. Just like epiblast cells immediately before gastrulation, fPSCs can efficiently differentiate into three germ layers and primordial germ cells (PGCs) in vitro. Thus, fPSCs highlight the feasibility of using PSCs to explore the development of mammalian epiblast.

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Isolation, Culture and Identification of Bovine Skeletal Stem Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2816 ◽

2021 ◽

Vol 11 (12) ◽

pp. 2337-2345

Author(s):

Junhui Lai ◽

Qin Yang ◽

Ruining Liang ◽

Weijun Guan ◽

Xiuxia Li

Keyword(s):

Stem Cells ◽

Cell Surface ◽

Bone Formation ◽

Growth Plate ◽

Bone Development ◽

Long Bone ◽

Biological Characterization ◽

Self Renewal ◽

And Cartilage

The growth plate is essential in long bone formation and contains a wealth of skeletal stem cells (SSCs). Though the origin and the mechanism for SSCs generation remain uncertain, recent studies demonstrate the transition from cartilage to bone that in the lineage for bone development. SSCs possesses the ability to differentiate into bone and cartilage in vitro. In this research, we aimed to isolate and culture the skeletal stem cells from bovine cattle and then studied its biological characterization. The results showed that these bovine SSCs are positive for PDPN+CD73+CD164+CD90+CD44+ cell surface bio-markers, they are capable of self-renewal and differentiation. Our dates proved that SSCs exists in bovine’s long bone.

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Protocol for controlled modeling of human epiblast and amnion development using stem cells

10.21203/rs.2.11520/v1 ◽

2019 ◽

Cited By ~ 2

Author(s):

Yi Zheng ◽

Jianping Fu

Keyword(s):

Stem Cells ◽

Primordial Germ Cells ◽

Primitive Streak ◽

Human Embryos ◽

Vitro Fertilization ◽

Human Embryology ◽

Post Implantation ◽

Advance Knowledge ◽

Early Human

Abstract Due to the inaccessibility of post-implantation human embryos and the restriction on in-vitro fertilization (IVF) embryos cultured beyond 14 days, the knowledge of early post-implantation human embryogenesis remains extremely limited. Recently, we have developed a microfluidic in-vitro platform, based on human pluripotent stem cells (hPSCs), which is capable of recapitulating several key developmental landmarks of early human post-implantation embryonic development, including lumenogenesis of the epiblast (EPI), amniogenesis, and specification of primordial germ cells (PGCs) and of primitive streak (PS) cells. Given its controllability and reproducibility, the microfluidic platform provides a powerful experimental platform to advance knowledge of human embryology and reproduction. This protocol describes the preparation of the microfluidic device and its implementation for modeling human post-implantation epiblast and amnion development using hPSCs.

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YAP regulates porcine skin-derived stem cells self-renewal partly by repressing Wnt/β-catenin signaling pathway

10.21203/rs.3.rs-414853/v1 ◽

2021 ◽

Author(s):

Hong-Chen Yan ◽

Yu Sun ◽

Ming-Yu Zhang ◽

Shu-Er Zhang ◽

Jia-Dong Sun ◽

...

Keyword(s):

Stem Cells ◽

Signaling Pathway ◽

Adult Stem Cells ◽

Self Renewal ◽

Human Ascs ◽

Regulation Mechanisms ◽

Interfering Rna ◽

Pluripotency Genes

Abstract Background Skin-derived stem cells (SDSCs) are a class of adult stem cells (ASCs) that have the ability to self-renew and differentiate. The regulation mechanisms involved in the differentiation of ASCs is a hot topic. Porcine models have close similarities to humans and porcine SDSCs (pSDSCs) offer an ideal in vitro model to investigate human ASCs. To date, studies concerning the role of yes-associated protein (YAP) in ASCs are limited, and the mechanism of its influence on self-renewal and differentiation of ASCs remain unclear. In this paper, we explore the link between the transcriptional regulator YAP and the fate of pSDSCs. Results We found that YAP promotes the pluripotent state of pSDSCs by maintaining the high expression of the pluripotency genes Sox2, Oct4. The overexpression of YAP prevented the differentiation of pSDSCs and the depletion of YAP by small interfering RNA (siRNAs) suppressed the self-renewal of pSDSCs. In addition, we found that YAP regulates the fate of pSDSCs through a mechanism related to the Wnt/β-catenin signaling pathway. When an activator of the Wnt/β-catenin signaling pathway, CHIR99021, was added to pSDSCs overexpressing YAP the ability of pSDSCs to differentiate was partially restored. Conversely, when XAV939 an inhibitor of Wnt/β-catenin signaling pathway, was added to YAP knockdown pSDSCs a higher self-renewal ability resulted. Conclusions our results suggested that, YAP and the Wnt/β-catenin signaling pathway interact to regulate the fate of pSDSCs.

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