High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures
During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and ex...
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eLife Sciences Publications Ltd
2020-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/59445 |
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| author | Kyaw Thu Minn Yuheng C Fu Shenghua He Sabine Dietmann Steven C George Mark A Anastasio Samantha A Morris Lilianna Solnica-Krezel |
| author_facet | Kyaw Thu Minn Yuheng C Fu Shenghua He Sabine Dietmann Steven C George Mark A Anastasio Samantha A Morris Lilianna Solnica-Krezel |
| author_sort | Kyaw Thu Minn |
| collection | DOAJ |
| description | During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells in radial arrangement. Using single-cell RNA sequencing and cross-species comparisons with mouse, cynomolgus monkey gastrulae, and post-implantation human embryos, we reveal that gastruloids contain cells transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial germ cells, trophectoderm, and amnion. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell types. Ectodermal cells segregated from endodermal and extraembryonic but mixed with mesodermal cells. Our work demonstrates that the gastruloid system models primate-specific features of embryogenesis, and that gastruloid cells exhibit evolutionarily conserved sorting behaviors. This work generates a resource for transcriptomes of human extraembryonic and embryonic germ layers differentiated in a stereotyped arrangement. |
| first_indexed | 2024-04-12T02:43:24Z |
| format | Article |
| id | doaj.art-c34323156d4f42b1bfaa49c57b05a1d8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:43:24Z |
| publishDate | 2020-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c34323156d4f42b1bfaa49c57b05a1d82022-12-22T03:51:16ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.59445High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid culturesKyaw Thu Minn0Yuheng C Fu1https://orcid.org/0000-0001-8037-6398Shenghua He2Sabine Dietmann3Steven C George4Mark A Anastasio5Samantha A Morris6https://orcid.org/0000-0001-8561-4340Lilianna Solnica-Krezel7https://orcid.org/0000-0003-0983-221XDepartment of Biomedical Engineering, Washington University, St. Louis, United States; Department of Developmental Biology, Washington University School of Medicine, St. Louis, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United States; Department of Genetics, Washington University School of Medicine, St. Louis, United States; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, United StatesDepartment of Computer Science & Engineering, Washington University, St. Louis, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United States; Division of Nephrology, Washington University School of Medicine, St. Louis, United States; Institute for Informatics, Washington University School of Medicine, St. Louis, United StatesDepartment of Biomedical Engineering, University of California, Davis, Davis, United StatesDepartment of Biomedical Engineering, Washington University, St. Louis, United States; Department of Bioengineering, University of Illinois, Urbana-Champaign, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United States; Department of Genetics, Washington University School of Medicine, St. Louis, United States; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, United StatesDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, United States; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, United StatesDuring mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells in radial arrangement. Using single-cell RNA sequencing and cross-species comparisons with mouse, cynomolgus monkey gastrulae, and post-implantation human embryos, we reveal that gastruloids contain cells transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial germ cells, trophectoderm, and amnion. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell types. Ectodermal cells segregated from endodermal and extraembryonic but mixed with mesodermal cells. Our work demonstrates that the gastruloid system models primate-specific features of embryogenesis, and that gastruloid cells exhibit evolutionarily conserved sorting behaviors. This work generates a resource for transcriptomes of human extraembryonic and embryonic germ layers differentiated in a stereotyped arrangement.https://elifesciences.org/articles/59445gastrulationgerm layerscell sortingprimordial germ cellsamniontrophectoderm |
| spellingShingle | Kyaw Thu Minn Yuheng C Fu Shenghua He Sabine Dietmann Steven C George Mark A Anastasio Samantha A Morris Lilianna Solnica-Krezel High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures eLife gastrulation germ layers cell sorting primordial germ cells amnion trophectoderm |
| title | High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures |
| title_full | High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures |
| title_fullStr | High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures |
| title_full_unstemmed | High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures |
| title_short | High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures |
| title_sort | high resolution transcriptional and morphogenetic profiling of cells from micropatterned human esc gastruloid cultures |
| topic | gastrulation germ layers cell sorting primordial germ cells amnion trophectoderm |
| url | https://elifesciences.org/articles/59445 |
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