Dlp-mediated Hh and Wnt signaling interdependence is critical in the niche for germline stem cell progeny differentiation

Although multiple signaling pathways work synergistically in various niches to control stem cell self-renewal and differentiation, it remains poorly understood how they cooperate with one another molecularly. In the Drosophila ovary, Hh and Wnt pathways function in the niche to promote germline stem cell (GSC) progeny differentiation. Here, we show that glypican Dlp-mediated Hh and Wnt signaling interdependence operates in the niche to promote GSC progeny differentiation by preventing BMP signaling. Hh/Wnt-mediated dlp repression is essential for their signaling interdependence in niche cells and for GSC progeny differentiation by preventing BMP signaling. Mechanistically, Hh and Wnt downstream transcription factors directly bind to the same dlp regulatory region and recruit corepressors composed of transcription factor Croc and Egg/H3K9 trimethylase to repress Dlp expression. Therefore, our study reveals a novel mechanism for Hh/Wnt signaling–mediated direct dlp repression and a novel regulatory mechanism for Dlp-mediated Hh/Wnt signaling interdependence in the GSC differentiation niche.

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The Osa-Containing SWI/SNF Chromatin-Remodeling Complex Is Required in the Germline Differentiation Niche for Germline Stem Cell Progeny Differentiation

Genes ◽

10.3390/genes12030363 ◽

2021 ◽

Vol 12 (3) ◽

pp. 363

Author(s):

Xiaolong Hu ◽

Mengjie Li ◽

Xue Hao ◽

Yi Lu ◽

Lei Zhang ◽

...

Keyword(s):

Stem Cell ◽

Bmp Signaling ◽

Germline Stem Cell ◽

Dependent Manner ◽

Self Renewal ◽

Cellular Processes ◽

Lineage Differentiation ◽

Chromatin Remodeling Complex ◽

Germline Differentiation ◽

Drosophila Ovary

The Drosophila ovary is recognized as a powerful model to study stem cell self-renewal and differentiation. Decapentaplegic (Dpp) is secreted from the germline stem cell (GSC) niche to activate Bone Morphogenic Protein (BMP) signaling in GSCs for their self-renewal and is restricted in the differentiation niche for daughter cell differentiation. Here, we report that Switch/sucrose non-fermentable (SWI/SNF) component Osa depletion in escort cells (ECs) results in a blockage of GSC progeny differentiation. Further molecular and genetic analyses suggest that the defective germline differentiation is partially attributed to the elevated dpp transcription in ECs. Moreover, ectopic Engrailed (En) expression in osa-depleted ECs partially contributes to upregulated dpp transcription. Furthermore, we show that Osa regulates germline differentiation in a Brahma (Brm)-associated protein (BAP)-complex-dependent manner. Additionally, the loss of EC long cellular processes upon osa depletion may also partly contribute to the germline differentiation defect. Taken together, these data suggest that the epigenetic factor Osa plays an important role in controlling EC characteristics and germline lineage differentiation.

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magu is required for germline stem cell self-renewal through BMP signaling in the Drosophila testis

Developmental Biology ◽

10.1016/j.ydbio.2011.06.022 ◽

2011 ◽

Vol 357 (1) ◽

pp. 202-210 ◽

Cited By ~ 28

Author(s):

Qi Zheng ◽

Yiwen Wang ◽

Eric Vargas ◽

Stephen DiNardo

Keyword(s):

Stem Cell ◽

Bmp Signaling ◽

Germline Stem Cell ◽

Self Renewal ◽

Drosophila Testis

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Ecdysone signaling promotes expression of multifunctional RNA binding proteins essential for ovarian germline stem cell self-renewal in Drosophila

10.1101/321109 ◽

2018 ◽

Author(s):

Danielle S. Finger ◽

Vivian V. Holt ◽

Elizabeth T. Ables

Keyword(s):

Stem Cell ◽

Molecular Mechanisms ◽

Rna Binding ◽

Rna Binding Proteins ◽

Bmp Signaling ◽

Germline Stem Cell ◽

Self Renewal ◽

Bmp Receptors ◽

Morphogenetic Protein ◽

Ecdysone Signaling

ABSTRACTSteroid hormones promote stem cell self-renewal in many tissues; however, the molecular mechanisms by which hormone signaling is integrated with niche-derived signals are largely uncharacterized. In the Drosophila ovary, the steroid hormone ecdysone promotes germline stem cell (GSC) self-renewal. Despite strong evidence that ecdysone modulates the reception of bone morphogenetic protein (BMP) signals in GSCs, transcriptional targets of ecdysone signaling that facilitate BMP reception are unknown. Here, we report that ecdysone signaling promotes the expression of the heterogeneous nuclear ribonucleoproteins (hnRNPs) squid, hephaestus, Hrb27C, and Hrb87F in GSCs. These hnRNPs functionally interact with ecdysone signaling to control GSC number and are cell autonomously required in GSCs for their maintenance. We demonstrate that hnRNPs promote GSC self-renewal by binding to transcripts essential for proper BMP signaling, including the BMP receptors thickveins and punt. Our findings support the model that stem cells coordinate local and long-range signals at the transcriptional and post-transcriptional levels to maintain self-renewal in response to physiological demand.GRAPHICAL ABSTRACTEcdysone signaling regulates distinct hnRNPs that bind to BMP signaling targets to control GSC self-renewal.SUMMARY STATEMENTEcdysone signaling promotes expression of heterogeneous ribonucleoproteins that modulate BMP-dependent germline stem cell self-renewal in the Drosophila ovary.

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The Wnt pathway limits BMP signaling outside of the germline stem cell niche in Drosophila ovaries

Developmental Biology ◽

10.1016/j.ydbio.2016.06.038 ◽

2016 ◽

Vol 417 (1) ◽

pp. 50-62 ◽

Cited By ~ 34

Author(s):

Violaine I. Mottier-Pavie ◽

Victor Palacios ◽

Susan Eliazer ◽

Shane Scoggin ◽

Michael Buszczak

Keyword(s):

Stem Cell ◽

Stem Cell Niche ◽

Wnt Pathway ◽

Bmp Signaling ◽

Germline Stem Cell ◽

Cell Niche ◽

Germline Stem Cell Niche

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Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation

Nature Communications ◽

10.1038/ncomms9856 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 19

Author(s):

Jin Sun ◽

Hui-Min Wei ◽

Jiang Xu ◽

Jian-Feng Chang ◽

Zhihao Yang ◽

...

Keyword(s):

Stem Cell ◽

Epigenetic Regulation ◽

Histone H1 ◽

Germline Stem Cell ◽

Self Renewal ◽

H4k16 Acetylation

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BMP Signaling and Stem Cell Self-Renewal in the Drosophila Ovary

Principles of Developmental Genetics ◽

10.1016/b978-0-12-405945-0.00005-3 ◽

2015 ◽

pp. 77-96

Author(s):

Darin Dolezal ◽

Francesca Pignoni

Keyword(s):

Stem Cell ◽

Bmp Signaling ◽

Self Renewal ◽

Drosophila Ovary

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Silencing of long noncoding RNA HOXA11-AS inhibits the Wnt signaling pathway via the upregulation of HOXA11 and thereby inhibits the proliferation, invasion, and self-renewal of hepatocellular carcinoma stem cells

Experimental & Molecular Medicine ◽

10.1038/s12276-019-0328-x ◽

2019 ◽

Vol 51 (11) ◽

pp. 1-20 ◽

Cited By ~ 2

Author(s):

Jun-Cheng Guo ◽

Yi-Jun Yang ◽

Jin-Fang Zheng ◽

Jian-Quan Zhang ◽

Min Guo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Stem Cells ◽

Stem Cell ◽

Wnt Signaling ◽

Signaling Pathway ◽

Methylation Level ◽

Wnt Signaling Pathway ◽

The Self ◽

Self Renewal

AbstractHepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.

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