A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass
There remains much that we do not understand about the earliest stages of human development. On a gross level, there is evidence for apoptosis, but the nature of the affected cell types is unknown. Perhaps most importantly, the inner cell mass (ICM), from which the foetus is derived and hence of int...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-06-01
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| Series: | PLoS Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281584/?tool=EBI |
| _version_ | 1797797895713325056 |
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| author | Manvendra Singh Aleksandra M. Kondrashkina Thomas J. Widmann Jose L. Cortes Vikas Bansal Jichang Wang Christine Römer Marta Garcia-Canadas Jose L. Garcia-Perez Laurence D. Hurst Zsuzsanna Izsvák |
| author_facet | Manvendra Singh Aleksandra M. Kondrashkina Thomas J. Widmann Jose L. Cortes Vikas Bansal Jichang Wang Christine Römer Marta Garcia-Canadas Jose L. Garcia-Perez Laurence D. Hurst Zsuzsanna Izsvák |
| author_sort | Manvendra Singh |
| collection | DOAJ |
| description | There remains much that we do not understand about the earliest stages of human development. On a gross level, there is evidence for apoptosis, but the nature of the affected cell types is unknown. Perhaps most importantly, the inner cell mass (ICM), from which the foetus is derived and hence of interest in reproductive health and regenerative medicine, has proven hard to define. Here, we provide a multi-method analysis of the early human embryo to resolve these issues. Single-cell analysis (on multiple independent datasets), supported by embryo visualisation, uncovers a common previously uncharacterised class of cells lacking commitment markers that segregates after embryonic gene activation (EGA) and shortly after undergo apoptosis. The discovery of this cell type allows us to clearly define their viable ontogenetic sisters, these being the cells of the ICM. While ICM is characterised by the activity of an Old non-transposing endogenous retrovirus (HERVH) that acts to suppress Young transposable elements, the new cell type, by contrast, expresses transpositionally competent Young elements and DNA-damage response genes. As the Young elements are RetroElements and the cells are excluded from the developmental process, we dub these REject cells. With these and ICM being characterised by differential mobile element activities, the human embryo may be a “selection arena” in which one group of cells selectively die, while other less damaged cells persist. The inner cell mass, from which the human foetus is derived and hence of interest in reproductive health and regenerative medicine, has proven hard to define. Single-cell analysis and embryo visualization reveal a common novel class of non-committed cells that undergo apoptosis and may reflect a quality control screening process. |
| first_indexed | 2024-03-13T03:56:18Z |
| format | Article |
| id | doaj.art-c79ae257f97a464eb8488ff58e3fdc6f |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-03-13T03:56:18Z |
| publishDate | 2023-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-c79ae257f97a464eb8488ff58e3fdc6f2023-06-22T05:31:00ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-06-01216A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell massManvendra SinghAleksandra M. KondrashkinaThomas J. WidmannJose L. CortesVikas BansalJichang WangChristine RömerMarta Garcia-CanadasJose L. Garcia-PerezLaurence D. HurstZsuzsanna IzsvákThere remains much that we do not understand about the earliest stages of human development. On a gross level, there is evidence for apoptosis, but the nature of the affected cell types is unknown. Perhaps most importantly, the inner cell mass (ICM), from which the foetus is derived and hence of interest in reproductive health and regenerative medicine, has proven hard to define. Here, we provide a multi-method analysis of the early human embryo to resolve these issues. Single-cell analysis (on multiple independent datasets), supported by embryo visualisation, uncovers a common previously uncharacterised class of cells lacking commitment markers that segregates after embryonic gene activation (EGA) and shortly after undergo apoptosis. The discovery of this cell type allows us to clearly define their viable ontogenetic sisters, these being the cells of the ICM. While ICM is characterised by the activity of an Old non-transposing endogenous retrovirus (HERVH) that acts to suppress Young transposable elements, the new cell type, by contrast, expresses transpositionally competent Young elements and DNA-damage response genes. As the Young elements are RetroElements and the cells are excluded from the developmental process, we dub these REject cells. With these and ICM being characterised by differential mobile element activities, the human embryo may be a “selection arena” in which one group of cells selectively die, while other less damaged cells persist. The inner cell mass, from which the human foetus is derived and hence of interest in reproductive health and regenerative medicine, has proven hard to define. Single-cell analysis and embryo visualization reveal a common novel class of non-committed cells that undergo apoptosis and may reflect a quality control screening process.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281584/?tool=EBI |
| spellingShingle | Manvendra Singh Aleksandra M. Kondrashkina Thomas J. Widmann Jose L. Cortes Vikas Bansal Jichang Wang Christine Römer Marta Garcia-Canadas Jose L. Garcia-Perez Laurence D. Hurst Zsuzsanna Izsvák A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass PLoS Biology |
| title | A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass |
| title_full | A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass |
| title_fullStr | A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass |
| title_full_unstemmed | A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass |
| title_short | A new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass |
| title_sort | new human embryonic cell type associated with activity of young transposable elements allows definition of the inner cell mass |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281584/?tool=EBI |
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