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Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells
The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional f...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621967/ https://www.ncbi.nlm.nih.gov/pubmed/34831338 http://dx.doi.org/10.3390/cells10113111 |
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author | Lin, Po-Yu Yang, Denny Chuang, Chi-Hsuan Lin, Hsuan Chen, Wei-Ju Chen, Chia-Ying Chuang, Trees-Juen Lai, Chien-Ying Li, Long-Yuan Schuyler, Scott C. Lu, Frank Leigh Liu, Yu-Chuan Lu, Jean |
author_facet | Lin, Po-Yu Yang, Denny Chuang, Chi-Hsuan Lin, Hsuan Chen, Wei-Ju Chen, Chia-Ying Chuang, Trees-Juen Lai, Chien-Ying Li, Long-Yuan Schuyler, Scott C. Lu, Frank Leigh Liu, Yu-Chuan Lu, Jean |
author_sort | Lin, Po-Yu |
collection | PubMed |
description | The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro. The TBLCs exhibited totipotency transcriptionally and acquired expanded developmental potential with the ability to yield various embryonic and extraembryonic tissues that may be employed as novel mouse developmental cell models. However, it is disputed whether TBLCs are ‘true’ totipotent stem cells equivalent to in vivo two-cell stage embryos. To address this question, single-cell RNA sequencing was applied to TBLCs and cells from early mouse embryonic developmental stages and the data were integrated using canonical correlation analyses. Differential expression analyses were performed between TBLCs and multi-embryonic cell stages to identify differentially expressed genes. Remarkably, a subpopulation within the TBLCs population expressed a high level of the totipotent-related genes Zscan4s and displayed transcriptomic features similar to mouse two-cell stage embryonic cells. This study underscores the subtle differences between in vitro derived TBLCs and in vivo mouse early developmental cell stages at the single-cell transcriptomic level. Our study has identified a new experimental model for stem cell biology, namely ‘cluster 3’, as a subpopulation of TBLCs that can be molecularly defined as near totipotent cells. |
format | Online Article Text |
id | pubmed-8621967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86219672021-11-27 Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells Lin, Po-Yu Yang, Denny Chuang, Chi-Hsuan Lin, Hsuan Chen, Wei-Ju Chen, Chia-Ying Chuang, Trees-Juen Lai, Chien-Ying Li, Long-Yuan Schuyler, Scott C. Lu, Frank Leigh Liu, Yu-Chuan Lu, Jean Cells Article The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro. The TBLCs exhibited totipotency transcriptionally and acquired expanded developmental potential with the ability to yield various embryonic and extraembryonic tissues that may be employed as novel mouse developmental cell models. However, it is disputed whether TBLCs are ‘true’ totipotent stem cells equivalent to in vivo two-cell stage embryos. To address this question, single-cell RNA sequencing was applied to TBLCs and cells from early mouse embryonic developmental stages and the data were integrated using canonical correlation analyses. Differential expression analyses were performed between TBLCs and multi-embryonic cell stages to identify differentially expressed genes. Remarkably, a subpopulation within the TBLCs population expressed a high level of the totipotent-related genes Zscan4s and displayed transcriptomic features similar to mouse two-cell stage embryonic cells. This study underscores the subtle differences between in vitro derived TBLCs and in vivo mouse early developmental cell stages at the single-cell transcriptomic level. Our study has identified a new experimental model for stem cell biology, namely ‘cluster 3’, as a subpopulation of TBLCs that can be molecularly defined as near totipotent cells. MDPI 2021-11-10 /pmc/articles/PMC8621967/ /pubmed/34831338 http://dx.doi.org/10.3390/cells10113111 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lin, Po-Yu Yang, Denny Chuang, Chi-Hsuan Lin, Hsuan Chen, Wei-Ju Chen, Chia-Ying Chuang, Trees-Juen Lai, Chien-Ying Li, Long-Yuan Schuyler, Scott C. Lu, Frank Leigh Liu, Yu-Chuan Lu, Jean Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells |
title | Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells |
title_full | Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells |
title_fullStr | Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells |
title_full_unstemmed | Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells |
title_short | Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells |
title_sort | comparative analyses of single-cell transcriptomic profiles between in vitro totipotent blastomere-like cells and in vivo early mouse embryonic cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621967/ https://www.ncbi.nlm.nih.gov/pubmed/34831338 http://dx.doi.org/10.3390/cells10113111 |
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