Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Non-cell-autonomous control of mouse gastruloid development by the ultra-conserved lncRNA T-UCstem1

Coppola, Arianna ; Amoroso, Filomena ; Saracino, Federica ; Andolfi, Gennaro ; Sozzi, Edoardo LU orcid ; Salerno, Paolo ; Zoppoli, Pietro ; Fiorenzano, Alessandro LU ; Merla, Giuseppe and Patriarca, Eduardo Jorge , et al. (2025) In EMBO Journal 44(24). p.7620-7648
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
DKK1, Gastruloids, Noncoding RNAs, T-UCstem1, WNT Pathway
in
EMBO Journal
volume
44
issue
24
pages
29 pages
publisher
Oxford University Press
external identifiers
  • pmid:41174250
  • scopus:105020316946
ISSN
0261-4189
DOI
10.1038/s44318-025-00558-2
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025.
id
27ab0554-5f8a-411b-a8e1-331e75364719
date added to LUP
2026-01-14 15:59:25
date last changed
2026-02-11 18:42:15
@article{27ab0554-5f8a-411b-a8e1-331e75364719,
  abstract     = {{<p>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.</p>}},
  author       = {{Coppola, Arianna and Amoroso, Filomena and Saracino, Federica and Andolfi, Gennaro and Sozzi, Edoardo and Salerno, Paolo and Zoppoli, Pietro and Fiorenzano, Alessandro and Merla, Giuseppe and Patriarca, Eduardo Jorge and Minchiotti, Gabriella and Fico, Annalisa}},
  issn         = {{0261-4189}},
  keywords     = {{DKK1; Gastruloids; Noncoding RNAs; T-UCstem1; WNT Pathway}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{24}},
  pages        = {{7620--7648}},
  publisher    = {{Oxford University Press}},
  series       = {{EMBO Journal}},
  title        = {{Non-cell-autonomous control of mouse gastruloid development by the ultra-conserved lncRNA T-UCstem1}},
  url          = {{http://dx.doi.org/10.1038/s44318-025-00558-2}},
  doi          = {{10.1038/s44318-025-00558-2}},
  volume       = {{44}},
  year         = {{2025}},
}