scholarly journals Mouse CHD4-NURD is Required for Neonatal Spermatogonia Survival and Normal Gonad Development.

2022 ◽  
Author(s):  
Rodrigo Orlandini de Castro ◽  
Luciana Previato ◽  
Agustin Carbajal ◽  
Victor Goitea ◽  
Courtney T. Griffin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Germ Cell ◽  
Gonad Development ◽  
Stem Cell Population ◽  
Nurd Complex ◽  
Stem Cell Maintenance ◽  
Downstream Target ◽  
Chromatin Remodeling Complexes ◽  
Spermatogonia Stem Cell

Abstract Testis development and sustained germ cell production in adults rely on the establishment and maintenance of spermatogonia stem cells and their proper differentiation into spermatocytes. Chromatin remodeling complexes regulate critical processes during gamete development by restricting or promoting accessibility of DNA repair and gene expression machineries to the chromatin. Here, we investigated the role of CHD4 and CHD3 catalytic subunits of the NURD complex during spermatogenesis. Germ cell-specific deletion of Chd4 early in gametogenesis, but not Chd3, resulted in arrested early gamete development due to failed cell survival of neonate undifferentiated spermatogonia stem cell population. Candidate assessment revealed that CHD4 controls expression of Dmrt1 and its downstream target Plzf, both described as prominent regulators of spermatogonia stem cell maintenance. Our results show the requirement of CHD4 in mammalian gametogenesis pointing to functions in gene expression early in the process.

scholarly journals CHD4-NURD controls spermatogonia survival and differentiation

2019 ◽  
Author(s):  
Rodrigo O. de Castro ◽  
Victor Goitea ◽  
Luciana Previato ◽  
Agustin Carbajal ◽  
Courtney T. Griffin ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Survival ◽  
Chromatin Remodeling ◽  
Male Gamete ◽  
Stem Cell Population ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Testis Development ◽  
Expression Of Genes ◽  
Chromatin Remodeling Complexes

AbstractTestis development and sustained germ cell production in adults rely on the establishment of spermatogonia stem cells and their proper differentiation into mature gametes. Control of these processes involves not only promoting the expression of genes required for cell survival and differentiation but also repressing other cell fates. This level of transcriptional control requires chromatin-remodeling complexes that restrict or promote transcription machinery. Here, we investigated the roles of the NUcleosome Remodeling and Deacetylase (NURD) complex during spermatogenesis. Our cellular and biochemical analyses revealed differential expression and composition of NURD subunits in gametocytes at different stages of testis development. Germ cell-specific deletion of the NURD catalytic component CHD4, but not CHD3, resulted in arrested early gamete development due to failed cell survival of the undifferentiated spermatogonia stem cell population. Genome-wide CHD4 chromatin localization and transcriptomic analyses revealed that CHD4 binds the promoters and regulates the expression of genes involved in spermatogonia cell survival and differentiation. These results uncover the requirements of CHD4 in mammalian gonad development, and point to unique roles for the NURD complex with respect to other chromatin remodelers during gamete development.Significance StatementGametogenesis is a fundamental developmental program required for sustained fertility and survival of all sexually reproducing species. The developing male gamete undergoes numerous cell divisions and developmental stage transitions that are carefully monitored by epigenetic mechanisms. One prominent mechanism is directed by chromatin remodeling complexes, which modify chromatin structure and thereby control fundamental cellular processes such as gene transcription. In this work, we focused in understanding the role of CHD4 and CHD3 proteins, catalytic subunits of the NURD chromatin-remodeling complex, in mouse gametogenesis. We find that CHD4 has an essential function in gametogenesis, with an absolute requirement for survival of spermatogonia populations in the developing testis. This is accompanied by CHD4-mediated transcriptional regulation of genes important for spermatogonia survival, and differentiation.

scholarly journals The actin-binding protein profilin is required for germline stem cell maintenance and germ cell enclosure by somatic cyst cells

Development ◽  
2013 ◽  
Vol 141 (1) ◽  
pp. 73-82 ◽  
Author(s):  
A. R. Shields ◽  
A. C. Spence ◽  
Y. M. Yamashita ◽  
E. L. Davies ◽  
M. T. Fuller
Keyword(s):  
Stem Cell ◽  
Germ Cell ◽  
Binding Protein ◽  
Actin Binding ◽  
Germline Stem Cell ◽  
Actin Binding Protein ◽  
Stem Cell Maintenance ◽  
Cyst Cells ◽  
Cell Maintenance

scholarly journals me31B regulates stem cell homeostasis by preventing excess dedifferentiation in the Drosophila male germline

2021 ◽  
Author(s):  
Lindy Jensen ◽  
Zsolt G. Venkei ◽  
George J. Watase ◽  
Bitarka Bisai ◽  
Scott Pletcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Critical Role ◽  
Stem Cell Population ◽  
Germline Stem Cells ◽  
Cell Identity ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Male Germline ◽  
Elevated Frequency

Tissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is speculated to underlie tumorigenesis. Therefore, this process must be tightly controlled. Here we show that a translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.

Evaluation of Novel Mouse-Specific Germ Cell Gene Expression in Embryonic Stem Cell-Derived Germ Cell-Like CellsIn Vitrowith Retinoic Acid Treatment

2018 ◽  
Vol 20 (4) ◽  
pp. 245-255 ◽  
Author(s):  
Maryam Gholamitabar Tabari ◽  
Seyed Gholam Ali Jorsaraei ◽  
Mohammad Ghasemzadeh-Hasankolaei ◽  
Ali Asghar Ahmadi ◽  
Mehdi Amirikia
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Retinoic Acid ◽  
Germ Cell ◽  
Embryonic Stem Cell ◽  
Acid Treatment ◽  
Embryonic Stem ◽  
Retinoic Acid Treatment ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals Ush regulates hemocyte-specific gene expression, fatty acid metabolism and cell cycle progression and cooperates with dNuRD to orchestrate hematopoiesis

2020 ◽  
Author(s):  
Jonathan Lenz ◽  
Robert Liefke ◽  
Julianne Funk ◽  
Samuel Shoup ◽  
Andrea Nist ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cell ◽  
Specific Gene ◽  
Cell Cycle Regulators ◽  
Cell Type ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Specific Gene Expression ◽  
Cell Type Specific

AbstractThe generation of lineage-specific gene expression programmes that alter proliferation capacity, metabolic profile and cell type-specific functions during differentiation from multipotent stem cells to specialised cell types is crucial for development. During differentiation gene expression programmes are dynamically modulated by a complex interplay between sequence-specific transcription factors, associated cofactors and epigenetic regulators. Here, we study U-shaped (Ush), a multi-zinc finger protein that maintains the multipotency of stem cell-like hemocyte progenitors during Drosophila hematopoiesis. Using genomewide approaches we reveal that Ush binds to promoters and enhancers and that it controls the expression of three gene classes that encode proteins relevant to stem cell-like functions and differentiation: cell cycle regulators, key metabolic enzymes and proteins conferring specific functions of differentiated hemocytes. We employ complementary biochemical approaches to characterise the molecular mechanisms of Ush-mediated gene regulation. We uncover distinct Ush isoforms one of which binds the Nucleosome Remodeling and Deacetylation (NuRD) complex using an evolutionary conserved peptide motif. Remarkably, the Ush/NuRD complex specifically contributes to the repression of lineage-specific genes but does not impact the expression of cell cycle regulators or metabolic genes. This reveals a mechanism that enables specific and concerted modulation of functionally related portions of a wider gene expression programme. Finally, we use genetic assays to demonstrate that Ush and NuRD regulate enhancer activity during hemocyte differentiation in vivo and that both cooperate to suppress the differentiation of lamellocytes, a highly specialised blood cell type. Our findings reveal that Ush coordinates proliferation, metabolism and cell type-specific activities by isoform-specific cooperation with an epigenetic regulator.

Investigations of Murine Embryonic Stem Cell Maintenance by Analyses of Culture Variables and Gene Expression

2007 ◽  
pp. 185-189
Author(s):  
James M. Piret ◽  
Clive H. Glover ◽  
Michael Marin ◽  
Mohammed A. S. Chaudhry ◽  
Connie J. Eaves ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Maintenance ◽  
Murine Embryonic Stem Cell ◽  
Cell Maintenance

scholarly journals Fine-Tuning of GLI Activity through Arginine Methylation: Its Mechanisms and Function

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1973
Author(s):  
Yoshinori Abe ◽  
Nobuyuki Tanaka
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Target Gene ◽  
Arginine Methylation ◽  
Protein Stabilization ◽  
Fine Tuning ◽  
Target Gene Expression ◽  
Stem Cell Maintenance ◽  
Cell Maintenance

The glioma-associated oncogene (GLI) family consists of GLI1, GLI2, and GLI3 in mammals. This family has important roles in development and homeostasis. To achieve these roles, the GLI family has widespread outputs. GLI activity is therefore strictly regulated at multiple levels, including via post-translational modifications for context-dependent GLI target gene expression. The protein arginine methyl transferase (PRMT) family is also associated with embryogenesis, homeostasis, and cancer mainly via epigenetic modifications. In the PRMT family, PRMT1, PRMT5, and PRMT7 reportedly regulate GLI1 and GLI2 activity. PRMT1 methylates GLI1 to upregulate its activity and target gene expression. Cytoplasmic PRMT5 methylates GLI1 and promotes GLI1 protein stabilization. Conversely, nucleic PRMT5 interacts with MENIN to suppress growth arrest-specific protein 1 expression, which assists Hedgehog ligand binding to Patched, indirectly resulting in downregulated GLI1 activity. PRMT7-mediated GLI2 methylation upregulates its activity through the dissociation of GLI2 and Suppressor of Fused. Together, PRMT1, PRMT5, and PRMT7 regulate GLI activity at multiple revels. Furthermore, the GLI and PRMT families have strong links with various cancers through cancer stem cell maintenance. Therefore, PRMT-mediated regulation of GLI activity would have important roles in cancer stem cell maintenance.

scholarly journals Musashi regulates follicle stem cell maintenance and epithelial niche homeostasis in the Drosophila ovary

2020 ◽  
Author(s):  
Nicole A. Siddall ◽  
Franca Casagranda ◽  
Nicole Dominado ◽  
James Heaney ◽  
Jessie M. Sutherland ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Wnt Pathway ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Stem Cell Population ◽  
Stem Cell Maintenance ◽  
Lineage Differentiation ◽  
Cell Niche ◽  
Drosophila Ovary

AbstractThe Musashi (Msi) family of RNA-binding proteins regulate maintenance and differentiation of stem cells in multiple tissues of different species. Here, we use the powerful system of the Drosophila ovary to uncover an intrinsic requirement for Msi in both the maintenance of the follicle stem cell population and regulation of the architecture of the follicle stem cell niche. Further, we demonstrate an associated G2 lag of cycling somatic cells within the niche when Msi function is abrogated. Additionally, we show that Msi interaction with the Wnt pathway influences differentiation of anterior germarial escort cells from cells within the follicle stem cell niche region. This provides further evidence that escort cells can be derived from follicle stem/precursor cells and that Msi regulates lineage differentiation of follicle stem cell daughters.

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