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| Status |
Public on Jun 20, 2024 |
| Title |
Retinoic acid induces human gastruloids with posterior embryo-like structures |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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-seq (scRNA-seq), 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.
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| Overall design |
Single-cell RNA-seq of human gastruloids and RA gastruloids
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| Contributor(s) |
Hamazaki N, Yang W, Kubo C, Qiu C, Martin BK, Garge RK, Regalado SG, Nichols , Lee C, Daza RM, Srivatsan S, Shendure J |
| Citation(s) |
39164488 |
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| Submission date |
Jul 18, 2022 |
| Last update date |
Sep 04, 2024 |
| Contact name |
Nobuhiko Hamazaki |
| E-mail(s) |
hamazaki0917@gmail.com
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| Organization name |
University of Washington
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| Department |
Genome Sciences
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| Street address |
Foege Building S-210 3720 15th Ave NE
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| City |
Seattle |
| State/province |
Washington |
| ZIP/Postal code |
98195 |
| Country |
USA |
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| Platforms (1) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA859692 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE208369_KO_merged.RDS.gz |
733.8 Mb |
(ftp)(http) |
RDS |
| GSE208369_RAW.tar |
3.8 Gb |
(http)(custom) |
TAR (of RDS) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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