The primitive endoderm supports lineage plasticity to enable regulative development
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 24,3 MB, PDF-dokument
Mammalian blastocyst formation involves the specification of the trophectoderm followed by the differentiation of the inner cell mass into embryonic epiblast and extra-embryonic primitive endoderm (PrE). During this time, the embryo maintains a window of plasticity and can redirect its cellular fate when challenged experimentally. In this context, we found that the PrE alone was sufficient to regenerate a complete blastocyst and continue post-implantation development. We identify an in vitro population similar to the early PrE in vivo that exhibits the same embryonic and extra-embryonic potency and can form complete stem cell-based embryo models, termed blastoids. Commitment in the PrE is suppressed by JAK/STAT signaling, collaborating with OCT4 and the sustained expression of a subset of pluripotency-related transcription factors that safeguard an enhancer landscape permissive for multi-lineage differentiation. Our observations support the notion that transcription factor persistence underlies plasticity in regulative development and highlight the importance of the PrE in perturbed development.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cell |
| Vol/bind | 187 |
| Udgave nummer | 15 |
| Sider (fra-til) | 4010-4029.e16 |
| Antal sider | 37 |
| ISSN | 0092-8674 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
We thank N. Festuccia for EKOiE ESCs; B. Hogan, M. Aragona, and I. Kaklamanou for the Pdgfra-CreERT2 and RosamT/mG mice; J. Martin Gonzalez, R.A.L. Barraza, and the Core Facility for Transgenic Mice for embryo generation and support; H. Wollmann, M. Michaut, A. Kalvisa, and the reNEW Genomics Platform for technical expertise, support, and use of instruments; and G. de la Cruz, P. van Dieken, and the reNEW Flow Cytometry Platform for technical expertise, support, and use of instruments. We also thank J.J. Zylicz, M. Pleasants Lowndes, and other members of the Brickman lab for fruitful discussions and critical comments on this manuscript. We thank Elena G. Bansh for producing illustrations for the graphical abstract. Work in the Brickman lab was funded by the Lundbeck Foundation (R370-2021-617, R198-2015-412, R400-2022-769, and R286-2018-1534), the Independent Research Fund Denmark (DFF-8020-00100B, DFF-0134-00022B, and DFF-2034-00025B), the Danish National Research Foundation (DNRF116), the Novo Nordisk Foundation (NNF210C0070898), and the European Union (ERC, SENCE, AdG 101097979). Work in the Manzanares lab was funded by the Spanish Ministerio de Ciencia e Innovaci\u00F3n (PID2020-115755GB-100 and CEX2021-001154-S). The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) is supported by the Novo Nordisk Foundation grant number NNF21CC0073729 and previously NNF17CC0027852. Conceptualization, M.L.-A. and J.M.B.; methodology, M.L.-A. A.C.S. A.R.-R. M. Perera, T.E.K. and J.M.B.; investigation, M.L.-A. A.C.S. A.R.-R. M. Perera, T.E.K. and A.B.; formal analysis, M.L.-A. M. Proks, and T.E.K.; data curation, M.L.-A. M. Proks, and T.E.K.; visualization, M.L-A.; writing \u2013 original draft, M.L.-A. and J.M.B.; writing \u2013 review & editing, M.L.-A. and J.M.B.; supervision, M.M. and J.M.B.; funding acquisition, M.L.-A. A.R.-R. M. Perera, M.M. and J.M.B. The authors declare no competing interests.
Funding Information:
We thank N. Festuccia for EKOiE ESCs; B. Hogan, M. Aragona, and I. Kaklamanou for the Pdgfra-CreER T2 and Rosa mT/mG mice; J. Martin Gonzalez, R.A.L. Barraza, and the Core Facility for Transgenic Mice for embryo generation and support; H. Wollmann, M. Michaut, A. Kalvisa, and the reNEW Genomics Platform for technical expertise, support, and use of instruments; and G. de la Cruz, P. van Dieken, and the reNEW Flow Cytometry Platform for technical expertise, support, and use of instruments. We also thank J.J. Zylicz, M. Pleasants Lowndes, and other members of the Brickman lab for fruitful discussions and critical comments on this manuscript. We thank Elena G. Bansh for producing illustrations for the graphical abstract. The work was funded by the Lundbeck Foundation ( R370-2021-617 , R198-2015-412 , and R286-2018-1534 ), the Independent Research Fund Denmark ( DFF-8020-00100B ), the Danish National Research Foundation ( DNRF116 ), the European Union (ERC, SENCE, 101097979 ), and the Spanish Ministerio de Ciencia e Innovaci\u00F3n ( PID2020-115755GB-100 and CEX2021-001154-S ). The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) is supported by the Novo Nordisk Foundation grant number NNF21CC0073729 and previously NNF17CC0027852 .
Publisher Copyright:
© 2024 The Authors
ID: 399748012