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| Status |
Public on Aug 21, 2023 |
| Title |
A Human Post-Implantation Embryoid Model Derived Ex Utero Solely from Genetically Unmodified Naïve PSCs (scRNA-Seq II) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Our ability to study early human post-implantation development remains highly limited due to the ethical and technical challenges associated with intrauterine development of the human embryo after implantation. Despite the great progress made on human blastoids or gastruloids, such elegant models do not constitute an integrated synthetic stem cell-derived embryoid models (SEMs) that includes all the key extra-embryonic tissues of the early pre-gastrulating implanted human conceptus (e.g. hypoblast, yolk-sac, trophoblasts, amnion and extraembryonic mesoderm), and thus, do not recapitulate post-implantation epiblast development within the context of these extra-embryonic compartments. Mouse naïve pluripotent stem cells (PSCs) have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation mouse SEMs, while bypassing the blastocyst-like stage, and eventually initiating organogenesis ex utero. Here, we implement critical adaptations to extend these finding in humans, using only genetically unmodified human naïve PSCs, circumventing the need for ectopic expression of lineage promoting transgenes. Such integrated human SEMs recapitulate all known compartments of early post-implantation stage human embryos, including epiblast, hypoblast, extra-embryonic mesoderm, and trophoblast surrounding the latter layers. The organized human SEMs recapitulate key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization (dpf, Carnegie stage 6a), such as bilaminar disk formation, epiblast lumenogenesis, amniogenesis, anterior-posterior symmetry breaking, PGC specification, primary and secondary yolk sac formation, and extra-embryonic mesoderm expansion that defines a chorionic cavity and a connective stalk. This new platform constitutes a tractable stem cell-based model for experimentally interrogating previously inaccessible windows of human early peri- and post-implantation development.
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| Overall design |
10X single-cell RNA-seq measured on two human naïve stem-cell populations that were maintained in either RCL medium (RPMI based medium supplemented with CHIR99021 and LIF and B27 WITHOUT Insulin) to induce PrE/ExEM cells, or in BAP(J) medium, to induce TE lineage.
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| Contributor(s) |
Oldak B, Wildschutz E, Bondarenko V, Novershtern N, Hanna JH |
| Citation(s) |
37673118 |
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| Submission date |
Aug 21, 2023 |
| Last update date |
Oct 26, 2023 |
| Contact name |
Noa Novershtern |
| E-mail(s) |
noa.novershtern@weizmann.ac.il
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| Organization name |
Weizmann Institute of Science
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| Department |
Molecular Genetics
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| Street address |
Weizmann Institute
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| City |
Rehovot |
| ZIP/Postal code |
7610001 |
| Country |
Israel |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (2) |
| GSM7727541 |
Human Naive Stem Cells, BAP(J) medium, maintained for 3 days |
| GSM7727542 |
Human Naive Stem Cells, RCL medium, maintained for 3 days |
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| This SubSeries is part of SuperSeries: |
| GSE239932 |
A Human Post-Implantation Embryoid Model Derived Ex Utero Solely from Genetically Unmodified Naïve PSCs |
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| Relations |
| BioProject |
PRJNA1007731 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE241348_filtered_feature_bc_matrix.tar.gz |
92.6 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
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