| Title: |
Non-cell-autonomous control of mouse gastruloid development by the ultra-conserved lncRNA T-UCstem1 |
| Authors: |
Coppola A.; Amoroso F.; Saracino F.; Andolfi G.; Sozzi E.; Salerno P.; Zoppoli P.; Fiorenzano A.; Merla G.; Patriarca E. J.; Minchiotti G.; Fico A. |
| Contributors: |
Coppola, A.; Amoroso, F.; Saracino, F.; Andolfi, G.; Sozzi, E.; Salerno, P.; Zoppoli, P.; Fiorenzano, A.; Merla, G.; Patriarca, E. J.; Minchiotti, G.; Fico, A. |
| Publication Year: |
2025 |
| Collection: |
IRIS Università degli Studi di Napoli Federico II |
| Subject Terms: |
DKK1; Gastruloid; Noncoding RNA; T-UCstem1; WNT Pathway |
| Description: |
The role of long non-coding RNAs (lncRNAs) in early mammalian embryogenesis remains unclear due to the complexity of the regulatory mechanisms involving lncRNAs and the limited availability of embryo samples. Stem cell-based models, such as mouse gastruloids, provide new ways to address these challenges. Here, we investigate the function of ultra-conserved lncRNA T-UCstem1 in mammalian body plan formation. Combining morphological and immunofluorescence imaging analyses with bulk and single-cell transcriptomics, we provide evidence indicating that T-UCstem1 is important for mouse gastruloid development and anteroposterior axis extension. T-UCstem1 depletion in gastruloids results in their aberrant development, with defects in the expression of differentiation markers and persistence of pluripotency gene expression. Our single-cell analyses reveal higher levels of cellular heterogeneity in T-UCstem1-knockdown gastruloids. The presence of cell populations co-expressing pluripotency and differentiation markers points to an important role of T-UCstem1 in the establishment and maintenance of cell identity. Mechanistically, we show that T-UCstem1 acts in a non-cell-autonomous manner through regulation of the Dickkopf-related protein 1 (DKK1)-dependent WNT pathway. Our study identifies a new role for an ultra-conserved lncRNA in gastruloid development and highlights gastruloids as a model system for studying lncRNAs in early development. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/wos/WOS:001605232400001; journal:EMBO JOURNAL; https://hdl.handle.net/11588/1017015 |
| DOI: |
10.1038/s44318-025-00558-2 |
| Availability: |
https://hdl.handle.net/11588/1017015; https://doi.org/10.1038/s44318-025-00558-2 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Dominio pubblico ; license uri:http://creativecommons.org/publicdomain/zero/1.0/ |
| Accession Number: |
edsbas.6B6D1B78 |
| Database: |
BASE |