Retinoic acid induces human gastruloids with posterior embryo-like structures.

Autor: Hamazaki N; Department of Genome Sciences, University of Washington, Seattle, WA, USA. hamazaki@uw.edu.; Department of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA. hamazaki@uw.edu.; Institute for Stem Cell & Regenerative Medicine, University of Washington, Seattle, WA, USA. hamazaki@uw.edu.; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA. hamazaki@uw.edu.; Seattle Hub for Synthetic Biology, Seattle, WA, USA. hamazaki@uw.edu., Yang W; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Seattle Hub for Synthetic Biology, Seattle, WA, USA., Kubo CA; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Seattle Hub for Synthetic Biology, Seattle, WA, USA., Qiu C; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Seattle Hub for Synthetic Biology, Seattle, WA, USA., Martin BK; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Seattle Hub for Synthetic Biology, Seattle, WA, USA., Garge RK; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA., Regalado SG; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Seattle Hub for Synthetic Biology, Seattle, WA, USA.; Medical Scientist Training Program, University of Washington, Seattle, WA, USA., Nichols EK; Department of Genome Sciences, University of Washington, Seattle, WA, USA., Pendyala S; Department of Genome Sciences, University of Washington, Seattle, WA, USA., Bradley N; Department of Genome Sciences, University of Washington, Seattle, WA, USA., Fowler DM; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA.; Department of Bioengineering, University of Washington, Seattle, WA, USA., Lee C; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Seattle Hub for Synthetic Biology, Seattle, WA, USA., Daza RM; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Seattle Hub for Synthetic Biology, Seattle, WA, USA., Srivatsan S; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA.; Fred Hutchinson Cancer Center, Seattle, WA, USA., Shendure J; Department of Genome Sciences, University of Washington, Seattle, WA, USA. shendure@uw.edu.; Institute for Stem Cell & Regenerative Medicine, University of Washington, Seattle, WA, USA. shendure@uw.edu.; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA. shendure@uw.edu.; Seattle Hub for Synthetic Biology, Seattle, WA, USA. shendure@uw.edu.; Howard Hughes Medical Institute, Seattle, WA, USA. shendure@uw.edu.; Allen Discovery Center for Cell Lineage Tracing, Seattle, WA, USA. shendure@uw.edu.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Aug 20. Date of Electronic Publication: 2024 Aug 20.
DOI: 10.1038/s41556-024-01487-8
Abstrakt: Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed of all three germ layers, human gastruloids do not morphologically resemble post-implantation human embryos. Here we show that an early pulse of retinoic acid (RA), together with later Matrigel, robustly induces human gastruloids with posterior embryo-like morphological structures, including a neural tube flanked by segmented somites and diverse cell types, including neural crest, neural progenitors, renal progenitors and myocytes. Through in silico staging based on single-cell RNA sequencing, we find that human RA-gastruloids progress further than other human or mouse embryo models, aligning to E9.5 mouse and CS11 cynomolgus monkey embryos. We leverage chemical and genetic perturbations of RA-gastruloids to confirm that WNT and BMP signalling regulate somite formation and neural tube length in the human context, while transcription factors TBX6 and PAX3 underpin presomitic mesoderm and neural crest, respectively. Looking forward, RA-gastruloids are a robust, scalable model for decoding early human embryogenesis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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