Fsh and Lh have common and distinct effects on gene expression in rainbow trout testis

The general rules established from mammalian species for the regulation of spermatogenesis by gonadotropins may not be fully relevant in fish. Particularly, Fsh is as potent as Lh to stimulate steroidogenesis and the Fsh receptor is expressed in Leydig cells. In seasonal breeders, Fsh is likely the major gonadotropin involved in spermatogenesis onset and Lh is required to support spermatogenesis progression and gamete release. However, the genes that relay the action of Fsh and Lh have been poorly investigated in fish. The present study was aimed at identifying gonadotropin-dependent genes expressed in the testis during fish puberty. We cultured pubertal trout testicular explants for 96 h, with or without gonadotropin, and analyzed transcriptome variations using microarrays. Fsh and Lh had similar effects on a large group of genes while other genes were preferentially regulated by one or the other gonadotropin. We showed that most of the responsive genes were expressed in somatic cells and exhibited relevant patterns during the seasonal reproductive cycle. Some genes preferentially modulated by Lh could be involved in testicular cell fate (pvrl1andbty) or sperm maturation (ehmt2andracgap1) and will deserve further examination. Besides Fsh's effects on the steroidogenic pathway, our study demonstrates that Fsh coordinates relevant stimulatory and inhibitory paracrine factors known to regulate early germ cell proliferation and differentiation. Some of these genes belong to major regulatory pathways including the Igf pathway (igf1b/igf3andigfbp6), the Tgfb pathway (amh,inha,inhba, andfstl3), the Wnt pathway (wisp1), and pleiotrophin (mdka).

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Bisphenol A alters differentiation of Leydig cells in the rabbit fetal testis

The International Journal of Developmental Biology ◽

10.1387/ijdb.200185hm ◽

2020 ◽

Vol 52 ◽

Author(s):

Alexis Paulina Ortega-García ◽

Verónica Díaz-Hernández ◽

Pedro Collazo-Saldaña ◽

Horacio Merchant-Larios

Keyword(s):

Bisphenol A ◽

Leydig Cells ◽

Serum Testosterone ◽

Disruptive Effect ◽

Paracrine Signaling ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Tissue Compartments ◽

Fetal Organs ◽

The Impact

The endocrine disruptor Bisphenol A (BPA) crosses the placental barrier and reaches the fetal organs, including the gonads. In the testis, fetal Leydig cells (FLC) produce testosterone required for the male phenotype and homeostatic cell-cell signaling in the developing testis. Although it is known that BPA affects cell proliferation and differentiation in FLC, results concerning the mechanism involved are contradictory, mainly due to differences among species. Fast developing fetal gonads of rodents lack cortex and medulla, whereas species with more extended gestation periods form these two tissue compartments. The rabbit provides a good subject for studying the disruptive effect of BPA in fetal Leydig and possible postnatal endocrine consequences in adult Leydig cells. Here, we investigated the impact of BPA administered to pregnant rabbits does, on the FLC population of the developing testes. Using qRT-PCR, we assessed the levels of SF1, CYP11A1, 3β-HSD, and androgen receptor (AR) genes, and levels of fetal serum testosterone were measured by ELISA. These levels correlated with both the mitotic activity and the ultrastructural differentiation of the FLC by confocal and electron microscopy, respectively. Results indicate that BPA alters the expression levels of essential genes involved in androgen paracrine signaling, modifies the proliferation and differentiation of the FLCs, and alters the levels of serum testosterone after birth. Thus, BPA may change the postnatal levels of serum testosterone due to the impaired FLC population formed by the proliferating stem and non-proliferating cytodifferentiated FLC.

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Hierarchically engineered fibrous scaffolds for bone regeneration

Journal of The Royal Society Interface ◽

10.1098/rsif.2013.0684 ◽

2013 ◽

Vol 10 (88) ◽

pp. 20130684 ◽

Cited By ~ 28

Author(s):

Nadège Sachot ◽

Oscar Castaño ◽

Miguel A. Mateos-Timoneda ◽

Elisabeth Engel ◽

Josep A. Planell

Keyword(s):

Cell Fate ◽

Sol Gel ◽

Surface Characteristics ◽

Inorganic Glass ◽

Stem Cell Fate ◽

Fibrous Scaffolds ◽

Novel Approach ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Physical And Chemical

Surface properties of biomaterials play a major role in the governing of cell functionalities. It is well known that mechanical, chemical and nanotopographic cues, for example, influence cell proliferation and differentiation. Here, we present a novel coating protocol to produce hierarchically engineered fibrous scaffolds with tailorable surface characteristics, which mimic bone extracellular matrix. Based on the sol–gel method and a succession of surface treatments, hollow electrospun polylactic acid fibres were coated with a silicon–calcium–phosphate bioactive organic–inorganic glass. Compared with pure polymeric fibres that showed a completely smooth surface, the coated fibres exhibited a nanostructured topography and greater roughness. They also showed improved hydrophilic properties and a Young's modulus sixfold higher than non-coated ones, while remaining fully flexible and easy to handle. Rat mesenchymal stem cells cultured on these fibres showed great cellular spreading and interactions with the material. This protocol can be transferred to other structures and glasses, allowing the fabrication of various materials with well-defined features. This novel approach represents therefore a valuable improvement in the production of artificial matrices able to direct stem cell fate through physical and chemical interactions.

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Hyperactive WNT/CTNNB1 signaling induces a competing cell proliferation and epidermal differentiation response in the mouse mammary epithelium

10.1101/2021.06.22.449461 ◽

2021 ◽

Author(s):

Larissa Mourao ◽

Amber L. Zeeman ◽

Katrin E. Wiese ◽

Anika Bongaarts ◽

Lieve L. Oudejans ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Fate ◽

De Novo ◽

Mammary Epithelium ◽

Mechanistic Explanation ◽

Tumor Formation ◽

Epidermal Differentiation ◽

Cell Proliferation And Differentiation ◽

Primary Mouse ◽

Proliferation And Differentiation

In the past forty years, the WNT/CTNNB1 signaling pathway has emerged as a key player in mammary gland development and homeostasis. While also evidently involved in breast cancer, much unclarity continues to surround its precise role in mammary tumor formation and progression. This is largely due to the fact that the specific and direct effects of hyperactive WNT/CTNNB1 signaling on the mammary epithelium remain unknown. Here we use a primary mouse mammary organoid culture system to close this fundamental knowledge gap. We show that hyperactive WNT/CTNNB1 signaling induces competing cell proliferation and differentiation responses. While proliferation is dominant at lower levels of WNT/CTNNB1 signaling activity, higher levels cause reprogramming towards an epidermal cell fate. We show that this involves de novo activation of the epidermal differentiation cluster (EDC) locus and we identify master regulatory transcription factors that likely control the process. This is the first time that the molecular and cellular dose-response effects of WNT/CTNNB1 signaling in the mammary epithelium have been dissected in such detail. Our analyses reveal that the mammary epithelium is exquisitely sensitive to small changes in WNT/CTNNB1 signaling and offer a mechanistic explanation for the squamous differentiation that is observed in some WNT/CTNNB1 driven tumors.

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Identification of a New Site of Sumoylation on Tel (ETV6) Uncovers a PIAS-Dependent Mode of Regulating Tel Function

Molecular and Cellular Biology ◽

10.1128/mcb.01159-07 ◽

2008 ◽

Vol 28 (7) ◽

pp. 2342-2357 ◽

Cited By ~ 21

Author(s):

M. Guy Roukens ◽

Mariam Alloul-Ramdhani ◽

Alfred C. O. Vertegaal ◽

Zeinab Anvarian ◽

Crina I. A. Balog ◽

...

Keyword(s):

Gene Expression ◽

Cell Fate ◽

Control Of Gene Expression ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Spatiotemporal Control ◽

Identification And Characterization ◽

In Cells

ABSTRACT Cell proliferation and differentiation are governed by a finely controlled balance between repression and activation of gene expression. The vertebrate Ets transcriptional repressor Tel (ETV6) and its invertebrate orthologue Yan, play pivotal roles in cell fate determination although the precise mechanisms by which repression of gene expression by these factors is achieved are not clearly defined. Here, we report the identification and characterization of the primary site of sumoylation of Tel, lysine 11 (K11), which is highly conserved in vertebrates (except Danio rerio). We demonstrate that in cells PIAS3 binds to Tel and stimulates sumoylation of K11 in the nucleus. Both Tel monomers and oligomers are efficiently sumoylated on K11 in vitro; but in cells only Tel oligomers are found conjugated with SUMO, whereas sumoylation of Tel monomers is transitory and appears to sensitize them for proteasomal degradation. Mechanistically, sumoylation of K11 inhibits repression of gene expression by full-length Tel. In accordance with this observation, we found that sumoylation impedes Tel association with DNA. By contrast, a Tel isoform lacking K11 (TelM43) is strongly repressive. This isoform results from translation from an alternative initiation codon (M43) that is common to all Tel proteins that also contain the K11 sumoylation consensus site. We find that PIAS3 may have a dual, context-dependent influence on Tel; it mediates Tel sumoylation, but it also augments Tel's repressive function in a sumoylation-independent fashion. Our data support a model that suggests that PIAS-mediated sumoylation of K11 and the emergence of TelM43 in early vertebrates are linked and that this serves to refine spatiotemporal control of gene expression by Tel by establishing a pool of Tel molecules that are available either to be recycled to reinforce repression of gene expression or are degraded in a regulated fashion.

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The emerging role of MEIS1 in cell proliferation and differentiation

AJP Cell Physiology ◽

10.1152/ajpcell.00422.2020 ◽

2020 ◽

Author(s):

Mingzhu Jiang ◽

Shuang Xu ◽

Mi Bai ◽

Aihua Zhang

Keyword(s):

Cell Proliferation ◽

Cell Fate ◽

Integration Site ◽

Leukemia Cells ◽

Cell Fate Specification ◽

Cardiomyocyte Proliferation ◽

Proliferative Effect ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation

Cell proliferation and differentiation are the foundation of reproduction and growth. Mistakes in these processes may affect cell survival, or cause cell cycle dysregulation, such as tumorigenesis, birth defects and degenerative diseases, or cell death. Myeloid ecotropic viral integration site 1 (MEIS1) was initially discovered in leukemic mice. Recent research identified MEIS1 as an important transcription factor that regulates cell proliferation and differentiation during cell fate commitment. MEIS1 has a pro-proliferative effect in leukemia cells; however, its overexpression in cardiomyocytes restrains neonatal and adult cardiomyocyte proliferation. Additionally, MEIS1 has carcinogenic or tumor suppressive effects in different neoplasms. Thus, this uncertainty suggests that MEIS1 has a unique function in cell proliferation and differentiation. In this review, we summarize the primary findings of MEIS1 in regulating cell proliferation and differentiation. Correlations between MEIS1 and cell fate specification might suggest MEIS1 as a therapeutic target for diseases.

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Notch-Directed Germ Cell Proliferation Is Mediated by Proteoglycan-Dependent Transcription

10.1101/2020.07.30.229997 ◽

2020 ◽

Author(s):

Sandeep Gopal ◽

Aqilah Amran ◽

Andre Elton ◽

Leelee Ng ◽

Roger Pocock

Keyword(s):

Cell Proliferation ◽

Germ Cell ◽

Cell Fate ◽

Notch Receptor ◽

Cell Fate Decisions ◽

Calcium Dependent ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Germline Proliferation ◽

Membrane Bound

Notch receptors are essential membrane-bound regulators of cell proliferation and differentiation in metazoa. In the nematode Caenorhabditis elegans, correct expression of GLP-1 (germline proliferation-1), a germline-expressed Notch receptor, is important for germ cell maintenance. However, mechanisms that regulate GLP-1 expression are undefined. Here, we demonstrate that an AP-2 transcription factor (APTF-2) regulates GLP-1 expression through calcium-dependent binding to a conserved motif in the glp-1 promoter. Our data reveals that SDN-1 (syndecan-1), a transmembrane proteoglycan, regulates a TRP calcium channel in the soma to modulate the interaction between APTF-2 and glp-1 promoter - thus providing a potential communication nexus between the germline and its somatic environment to control germ cell fate decisions.

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Nanotechnology Facilitated Cultured Neuronal Network and Its Applications

International Journal of Molecular Sciences ◽

10.3390/ijms22115552 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5552

Author(s):

Satnam Singh ◽

Sachin Mishra ◽

Song Juha ◽

Manojit Pramanik ◽

Parasuraman Padmanabhan ◽

...

Keyword(s):

Cell Fate ◽

Neuronal Network ◽

Neural Cells ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

3D Architecture ◽

Tools And Techniques ◽

Insight Into

The development of a biomimetic neuronal network from neural cells is a big challenge for researchers. Recent advances in nanotechnology, on the other hand, have enabled unprecedented tools and techniques for guiding and directing neural stem cell proliferation and differentiation in vitro to construct an in vivo-like neuronal network. Nanotechnology allows control over neural stem cells by means of scaffolds that guide neurons to reform synaptic networks in suitable directions in 3D architecture, surface modification/nanopatterning to decide cell fate and stimulate/record signals from neurons to find out the relationships between neuronal circuit connectivity and their pathophysiological functions. Overall, nanotechnology-mediated methods facilitate precise physiochemical controls essential to develop tools appropriate for applications in neuroscience. This review emphasizes the newest applications of nanotechnology for examining central nervous system (CNS) roles and, therefore, provides an insight into how these technologies can be tested in vitro before being used in preclinical and clinical research and their potential role in regenerative medicine and tissue engineering.

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Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and Cancer

Stem Cells International ◽

10.1155/2017/6301385 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Nickolas Steinauer ◽

Chun Guo ◽

Jinsong Zhang

Keyword(s):

Stem Cells ◽

Fusion Protein ◽

Cell Fate ◽

Lymphoblastic Leukemia ◽

In Vivo Studies ◽

Hematopoietic Stem ◽

Regulatory Pathways ◽

Domain Structures ◽

Proliferation And Differentiation

MTG16 (myeloid translocation gene on chromosome 16) and its related proteins, MTG8 and MTGR1, define a small family of transcriptional corepressors. These corepressors share highly conserved domain structures yet have distinct biological functions and tissue specificity. In vivo studies have shown that, of the three MTG corepressors, MTG16 is uniquely important for the regulation of hematopoietic stem/progenitor cell (HSPC) proliferation and differentiation. Apart from this physiological function, MTG16 is also involved in carcinomas and leukemias, acting as the genetic target of loss of heterozygosity (LOH) aberrations in breast cancer and recurrent translocations in leukemia. The frequent involvement of MTG16 in these disease etiologies implies an important developmental role for this transcriptional corepressor. Furthermore, mounting evidence suggests that MTG16 indirectly alters the disease course of several leukemias via its regulatory interactions with a variety of pathologic fusion proteins. For example, a recent study has shown that MTG16 can repress not only wild-type E2A-mediated transcription, but also leukemia fusion protein E2A-Pbx1-mediated transcription, suggesting that MTG16 may serve as a potential therapeutic target in acute lymphoblastic leukemia expressing the E2A-Pbx1 fusion protein. Given that leukemia stem cells share similar regulatory pathways with normal HSPCs, studies to further understand how MTG16 regulates cell proliferation and differentiation could lead to novel therapeutic approaches for leukemia treatment.

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Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis

Cancers ◽

10.3390/cancers11040555 ◽

2019 ◽

Vol 11 (4) ◽

pp. 555 ◽

Cited By ~ 7

Author(s):

Elke Kaemmerer ◽

Min Kyung Jeon ◽

Alexander Berndt ◽

Christian Liedtke ◽

Nikolaus Gassler

Keyword(s):

Stem Cells ◽

Wnt Signaling ◽

Cell Fate ◽

Wnt Pathway ◽

Paneth Cell ◽

Cell Types ◽

Intestinal Stem Cells ◽

Neoplastic Disease ◽

Intestinal Epithelial ◽

Proliferation And Differentiation

Proliferation and differentiation of intestinal epithelial cells is assisted by highly specialized and well-regulated signaling cascades. The Wnt pathway, which is one of the fundamental pathways in the intestine, contributes to the organization of proliferative intestinal crypts by positioning and cycling of intestinal stem cells and their derivatives. The Wnt pathway promotes differentiation of intestinal secretory cell types along the crypt-plateau and crypt-villus axis. In contrast to the Wnt pathway, the intestinal Notch cascade participates in cellular differentiation and directs progenitor cells towards an absorptive fate with diminished numbers of Paneth and goblet cells. Opposing activities of Notch and Wnt signaling in the regulation of intestinal stem cells and the enterocytic cell fate have been elucidated recently. In fact, targeting Notch was able to overcome tumorigenesis of intestinal adenomas, prevented carcinogenesis, and counteracted Paneth cell death in the absence of caspase 8. At present, pharmacological Notch inhibition is considered as an interesting tool targeting the intrinsic Wnt pathway activities in intestinal non-neoplastic disease and carcinogenesis.

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Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

Melatonin Research ◽

10.32794/mr11250059 ◽

2020 ◽

Vol 3 (2) ◽

pp. 216-242 ◽

Cited By ~ 1

Author(s):

Mayuri Shukla ◽

Areechun Sotthibundhu ◽

Piyarat Govitrapong

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Adult Neurogenesis ◽

Adult Brain ◽

Therapeutic Approaches ◽

Therapeutic Implications ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.

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