CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells
Upon progesterone stimulation, Endometrial Stromal Cells (EnSCs) undergo a differentiation program into secretory cells (decidualization) to release in abundance factors crucial for embryo implantation. We previously demonstrated that decidualization requires massive reshaping of the secretory pathw...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.986997/full |
| _version_ | 1811241005226131456 |
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| author | Daniele Pittari Marco Dalla Torre Marco Dalla Torre Elena Borini Barbara Hummel Ritwick Sawarkar Ritwick Sawarkar Claudia Semino Eelco van Anken Eelco van Anken Paola Panina-Bordignon Paola Panina-Bordignon Roberto Sitia Roberto Sitia Tiziana Anelli Tiziana Anelli |
| author_facet | Daniele Pittari Marco Dalla Torre Marco Dalla Torre Elena Borini Barbara Hummel Ritwick Sawarkar Ritwick Sawarkar Claudia Semino Eelco van Anken Eelco van Anken Paola Panina-Bordignon Paola Panina-Bordignon Roberto Sitia Roberto Sitia Tiziana Anelli Tiziana Anelli |
| author_sort | Daniele Pittari |
| collection | DOAJ |
| description | Upon progesterone stimulation, Endometrial Stromal Cells (EnSCs) undergo a differentiation program into secretory cells (decidualization) to release in abundance factors crucial for embryo implantation. We previously demonstrated that decidualization requires massive reshaping of the secretory pathway and, in particular, of the Golgi complex. To decipher the underlying mechanisms, we performed a time-course transcriptomic analysis of in vitro decidualizing EnSC. Pathway analysis shows that Gene Ontology terms associated with vesicular trafficking and early secretory pathway compartments are the most represented among those enriched for upregulated genes. Among these, we identified a cluster of co-regulated genes that share CREB3L1 and CREB3L2 binding elements in their promoter regions. Indeed, both CREB3L1 and CREB3L2 transcription factors are up-regulated during decidualization. Simultaneous downregulation of CREB3L1 and CREB3L2 impairs Golgi enlargement, and causes dramatic changes in decidualizing EnSC, including Golgi fragmentation, collagen accumulation in dilated Endoplasmic Reticulum cisternae, and overall decreased protein secretion. Thus, both CREB3L1 and CREB3L2 are required for Golgi reshaping and efficient protein secretion, and, as such, for successful decidualization. |
| first_indexed | 2024-04-12T13:29:29Z |
| format | Article |
| id | doaj.art-885c2620c1c54e078fe93b1eb321f404 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T13:29:29Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-885c2620c1c54e078fe93b1eb321f4042022-12-22T03:31:13ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-10-011010.3389/fcell.2022.986997986997CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cellsDaniele Pittari0Marco Dalla Torre1Marco Dalla Torre2Elena Borini3Barbara Hummel4Ritwick Sawarkar5Ritwick Sawarkar6Claudia Semino7Eelco van Anken8Eelco van Anken9Paola Panina-Bordignon10Paola Panina-Bordignon11Roberto Sitia12Roberto Sitia13Tiziana Anelli14Tiziana Anelli15Faculty of Medicine, Vita-Salute San Raffaele University, Milan, ItalyFaculty of Medicine, Vita-Salute San Raffaele University, Milan, ItalyDivision of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, ItalyFaculty of Medicine, Vita-Salute San Raffaele University, Milan, ItalyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, GermanyMedical Research Council (MRC), University of Cambridge, Cambridge, United KingdomDivision of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, ItalyFaculty of Medicine, Vita-Salute San Raffaele University, Milan, ItalyDivision of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, ItalyFaculty of Medicine, Vita-Salute San Raffaele University, Milan, ItalyDivision of Neuroscience, IRCCS Ospedale San Raffaele, Milan, ItalyFaculty of Medicine, Vita-Salute San Raffaele University, Milan, ItalyDivision of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, ItalyFaculty of Medicine, Vita-Salute San Raffaele University, Milan, ItalyDivision of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, ItalyUpon progesterone stimulation, Endometrial Stromal Cells (EnSCs) undergo a differentiation program into secretory cells (decidualization) to release in abundance factors crucial for embryo implantation. We previously demonstrated that decidualization requires massive reshaping of the secretory pathway and, in particular, of the Golgi complex. To decipher the underlying mechanisms, we performed a time-course transcriptomic analysis of in vitro decidualizing EnSC. Pathway analysis shows that Gene Ontology terms associated with vesicular trafficking and early secretory pathway compartments are the most represented among those enriched for upregulated genes. Among these, we identified a cluster of co-regulated genes that share CREB3L1 and CREB3L2 binding elements in their promoter regions. Indeed, both CREB3L1 and CREB3L2 transcription factors are up-regulated during decidualization. Simultaneous downregulation of CREB3L1 and CREB3L2 impairs Golgi enlargement, and causes dramatic changes in decidualizing EnSC, including Golgi fragmentation, collagen accumulation in dilated Endoplasmic Reticulum cisternae, and overall decreased protein secretion. Thus, both CREB3L1 and CREB3L2 are required for Golgi reshaping and efficient protein secretion, and, as such, for successful decidualization.https://www.frontiersin.org/articles/10.3389/fcell.2022.986997/fullsecretory pathwayvesicular transportdifferentiationtranscriptomics analysiscollagen |
| spellingShingle | Daniele Pittari Marco Dalla Torre Marco Dalla Torre Elena Borini Barbara Hummel Ritwick Sawarkar Ritwick Sawarkar Claudia Semino Eelco van Anken Eelco van Anken Paola Panina-Bordignon Paola Panina-Bordignon Roberto Sitia Roberto Sitia Tiziana Anelli Tiziana Anelli CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells Frontiers in Cell and Developmental Biology secretory pathway vesicular transport differentiation transcriptomics analysis collagen |
| title | CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells |
| title_full | CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells |
| title_fullStr | CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells |
| title_full_unstemmed | CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells |
| title_short | CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells |
| title_sort | creb3l1 and creb3l2 control golgi remodelling during decidualization of endometrial stromal cells |
| topic | secretory pathway vesicular transport differentiation transcriptomics analysis collagen |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.986997/full |
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