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

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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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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DNA damage-induced Lok/CHK2 activation compromises germline stem cell self-renewal and lineage differentiation

Development ◽

10.1242/dev.141069 ◽

2016 ◽

Vol 143 (23) ◽

pp. 4312-4323 ◽

Cited By ~ 22

Author(s):

Xing Ma ◽

Yingying Han ◽

Xiaoqing Song ◽

Trieu Do ◽

Zhihao Yang ◽

...

Keyword(s):

Dna Damage ◽

Stem Cell ◽

Germline Stem Cell ◽

Self Renewal ◽

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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Control of germline stem cell self-renewal and differentiation in the Drosophila ovary: concerted actions of niche signals and intrinsic factors

Wiley Interdisciplinary Reviews Developmental Biology ◽

10.1002/wdev.60 ◽

2012 ◽

Vol 2 (2) ◽

pp. 261-273 ◽

Cited By ~ 54

Author(s):

Xie Ting

Keyword(s):

Stem Cell ◽

Germline Stem Cell ◽

Self Renewal ◽

Intrinsic Factors ◽

Drosophila Ovary

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

Science Advances ◽

10.1126/sciadv.aaz0480 ◽

2020 ◽

Vol 6 (20) ◽

pp. eaaz0480 ◽

Cited By ~ 2

Author(s):

Renjun Tu ◽

Bo Duan ◽

Xiaoqing Song ◽

Ting Xie

Keyword(s):

Transcription Factor ◽

Stem Cell ◽

Wnt Signaling ◽

Regulatory Mechanism ◽

Regulatory Region ◽

Bmp Signaling ◽

Germline Stem Cell ◽

Self Renewal ◽

Wnt Pathways ◽

Multiple Signaling

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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BMP Signaling Is Required for Controlling Somatic Stem Cell Self-Renewal in the Drosophila Ovary

Developmental Cell ◽

10.1016/j.devcel.2005.09.013 ◽

2005 ◽

Vol 9 (5) ◽

pp. 651-662 ◽

Cited By ~ 66

Author(s):

Daniel Kirilly ◽

Eric P. Spana ◽

Norbert Perrimon ◽

Richard W. Padgett ◽

Ting Xie

Keyword(s):

Stem Cell ◽

Bmp Signaling ◽

Somatic Stem Cell ◽

Self Renewal ◽

Drosophila Ovary

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Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

Molecular and Cellular Biology ◽

10.1128/mcb.00121-15 ◽

2015 ◽

Vol 35 (10) ◽

pp. 1700-1711 ◽

Cited By ~ 15

Author(s):

Fenfang Chen ◽

Xia Lin ◽

Pinglong Xu ◽

Zhengmao Zhang ◽

Yanzhen Chen ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Mesenchymal Stem Cell ◽

Nuclear Export ◽

Stem Cell Differentiation ◽

Bmp Signaling ◽

Dependent Manner ◽

Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

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Wnt5a Signaling in Normal and Cancer Stem Cells

Stem Cells International ◽

10.1155/2017/5295286 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Yan Zhou ◽

Thomas J. Kipps ◽

Suping Zhang

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Target Cells ◽

Dependent Manner ◽

Self Renewal ◽

Surface Receptors ◽

Canonical Wnt

Wnt5a is involved in activating several noncanonical Wnt signaling pathways, which can inhibit or activate canonical Wnt/β-catenin signaling pathway in a receptor context-dependent manner. Wnt5a signaling is critical for regulating normal developmental processes, including stem cell self-renewal, proliferation, differentiation, migration, adhesion, and polarity. Moreover, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a signaling in regulating normal and cancer stem cell self-renewal, cancer cell proliferation, migration, and invasion. In this article, we review recent findings regarding the molecular mechanisms and roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or neoplastic breast or ovary, highlighting that Wnt5a may have different effects on target cells depending on the surface receptors expressed by the target cell.

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