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Neupane, J.* ; Lubatti, G. ; Gross-Thebing, T.* ; Ruiz Tejada Segura, M.L. ; Butler, R.H.* ; Gross-Thebing, S.* ; Dietmann, S.* ; Scialdone, A. ; Surani, M.A.*

The emergence of human primordial germ cell-like cells in stem cell-derived gastruloids.

Sci. Adv. 11:eado1350 (2025)
Publ. Version/Full Text Research data DOI PMC
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Most advances in early human postimplantation development depend on animal studies and stem cell-based embryo models. Here, we present self-organized three-dimensional human gastruloids (hGs) derived from embryonic stem cells. The transcriptome profile of day 3 hGs aligned with Carnegie stage 7 human gastrula, with cell types and differentiation trajectories consistent with human gastrulation. Notably, we observed the emergence of nascent primordial germ cell-like cells (PGCLCs), but without exogenous bone morphogenetic protein (BMP) signaling, which is essential for the PGCLC fate. A mutation in the ISL1 gene affects amnion-like cells and leads to a loss of PGCLCs; the addition of exogenous BMP2 rescues the PGCLC fate, indicating that the amnion may provide endogenous BMP signaling. Our model of early human embryogenesis will enable further exploration of the germ line and other early human lineages.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Blastocyst-like Structures; Differentiation; Fate; Specification; Commitment; Generation; Induction; Reveals
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Journal Science Advances
Quellenangaben Volume: 11, Issue: 13, Pages: , Article Number: eado1350 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Epigenetics and Stem Cells (IES)
Institute of Computational Biology (ICB)
Institute of Functional Epigenetics (IFE)
POF-Topic(s) 30204 - Cell Programming and Repair
30205 - Bioengineering and Digital Health
30203 - Molecular Targets and Therapies
Research field(s) Stem Cell and Neuroscience
Enabling and Novel Technologies
Helmholtz Diabetes Center
PSP Element(s) G-506290-001
G-506200-001
G-503800-001
G-502800-001
Grants Deutsche Forschungsgemeinschaft
Helmholtz Association
German National Academy of Sciences Leopoldina
Human Development Biology Initiative
Wellcome Senior Investigator Award in Science
DOI 10.1126/sciadv.ado1350
WOS ID 001452876500012
PubMed ID 40138398
Erfassungsdatum 2025-05-05
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