PRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferation
BMP signaling acts as an instructive cue in various developmental processes such as tissue patterning, stem cell proliferation, and differentiation. However, it is not fully understood how this signaling pathway generates different cell-specific outputs. Here, we have identified PRDM16 as a key co-f...
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eLife Sciences Publications Ltd
2025-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/104076 |
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| author | Li He Jiayu Wen Qi Dai |
| author_facet | Li He Jiayu Wen Qi Dai |
| author_sort | Li He |
| collection | DOAJ |
| description | BMP signaling acts as an instructive cue in various developmental processes such as tissue patterning, stem cell proliferation, and differentiation. However, it is not fully understood how this signaling pathway generates different cell-specific outputs. Here, we have identified PRDM16 as a key co-factor for BMP signaling in the mouse brain. PRDM16 contributes to a repressive role of BMP signaling on neural stem cell (NSC) proliferation. We demonstrate that PRDM16 regulates the genomic distribution of BMP pathway transcription factors, the SMAD4/pSMAD complex, preventing the activation of cell proliferation genes. When Prdm16 is lost, the SMAD complex relocates to nearby genomic regions, leading to abnormal upregulation of BMP target genes. This function of PRDM16 is also required for the specification of choroid plexus (ChP) epithelial cells. Through a single-cell resolution fluorescent in situ approach, we have observed that genes co-repressed by SMAD and PRDM16, such as Wnt7b and several cell cycle regulators, become overexpressed in Prdm16 mutant ChP. Our findings elucidate a mechanism through which SMAD4 and pSMAD1/5/8 repress gene expression. Moreover, our study suggests a regulatory circuit composed of BMP and Wnt signaling, along with PRDM16, in controlling stem cell behaviors. |
| format | Article |
| id | doaj-art-e3ff71304e6843469a9c477d3e65bebf |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-e3ff71304e6843469a9c477d3e65bebf2025-08-20T03:25:12ZengeLife Sciences Publications LtdeLife2050-084X2025-07-011410.7554/eLife.104076PRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferationLi He0https://orcid.org/0000-0002-4743-5410Jiayu Wen1https://orcid.org/0000-0003-1249-6456Qi Dai2https://orcid.org/0000-0002-2082-0693Department of Molecular Bioscience, the Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDivision of Genome Sciences and Cancer, The John Curtin School of Medical Research, The Australian National University and Australian Research Council Centre of Excellence for the Mathematical Analysis of Cellular Systems, Canberra, AustraliaDepartment of Molecular Bioscience, the Wenner-Gren Institute, Stockholm University, Stockholm, SwedenBMP signaling acts as an instructive cue in various developmental processes such as tissue patterning, stem cell proliferation, and differentiation. However, it is not fully understood how this signaling pathway generates different cell-specific outputs. Here, we have identified PRDM16 as a key co-factor for BMP signaling in the mouse brain. PRDM16 contributes to a repressive role of BMP signaling on neural stem cell (NSC) proliferation. We demonstrate that PRDM16 regulates the genomic distribution of BMP pathway transcription factors, the SMAD4/pSMAD complex, preventing the activation of cell proliferation genes. When Prdm16 is lost, the SMAD complex relocates to nearby genomic regions, leading to abnormal upregulation of BMP target genes. This function of PRDM16 is also required for the specification of choroid plexus (ChP) epithelial cells. Through a single-cell resolution fluorescent in situ approach, we have observed that genes co-repressed by SMAD and PRDM16, such as Wnt7b and several cell cycle regulators, become overexpressed in Prdm16 mutant ChP. Our findings elucidate a mechanism through which SMAD4 and pSMAD1/5/8 repress gene expression. Moreover, our study suggests a regulatory circuit composed of BMP and Wnt signaling, along with PRDM16, in controlling stem cell behaviors.https://elifesciences.org/articles/104076PRDM16BMP signalingWnt signalingstem cell proliferationchoroid plexus |
| spellingShingle | Li He Jiayu Wen Qi Dai PRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferation eLife PRDM16 BMP signaling Wnt signaling stem cell proliferation choroid plexus |
| title | PRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferation |
| title_full | PRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferation |
| title_fullStr | PRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferation |
| title_full_unstemmed | PRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferation |
| title_short | PRDM16 functions as a co-repressor in the BMP pathway to suppress neural stem cell proliferation |
| title_sort | prdm16 functions as a co repressor in the bmp pathway to suppress neural stem cell proliferation |
| topic | PRDM16 BMP signaling Wnt signaling stem cell proliferation choroid plexus |
| url | https://elifesciences.org/articles/104076 |
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