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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Po-Yu Lin, Denny Yang, Chi-Hsuan Chuang, Hsuan Lin, Wei-Ju Chen, Chia-Ying Chen, Trees-Juen Chuang, Chien-Ying Lai, Long-Yuan Li, Scott C. Schuyler, Frank Leigh Lu, Yu-Chuan Liu, Jean Lu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	totipotency embryonic stem cells totipotent blastomere-like cells 2-cell-like cells (2CLCs) spliceosome inhibitor pladienolide B Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8e094dcf1fb8434c986d0415f34f3a63
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8e094dcf1fb8434c986d0415f34f3a63
record_format	dspace
spelling	oai:doaj.org-article:8e094dcf1fb8434c986d0415f34f3a632021-11-25T17:11:38ZComparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells10.3390/cells101131112073-4409https://doaj.org/article/8e094dcf1fb8434c986d0415f34f3a632021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3111https://doaj.org/toc/2073-4409The 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 <i>Zscan4s</i> 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.Po-Yu LinDenny YangChi-Hsuan ChuangHsuan LinWei-Ju ChenChia-Ying ChenTrees-Juen ChuangChien-Ying LaiLong-Yuan LiScott C. SchuylerFrank Leigh LuYu-Chuan LiuJean LuMDPI AGarticletotipotencyembryonic stem cellstotipotent blastomere-like cells2-cell-like cells (2CLCs)spliceosome inhibitorpladienolide BBiology (General)QH301-705.5ENCells, Vol 10, Iss 3111, p 3111 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	totipotency embryonic stem cells totipotent blastomere-like cells 2-cell-like cells (2CLCs) spliceosome inhibitor pladienolide B Biology (General) QH301-705.5
spellingShingle	totipotency embryonic stem cells totipotent blastomere-like cells 2-cell-like cells (2CLCs) spliceosome inhibitor pladienolide B Biology (General) QH301-705.5 Po-Yu Lin Denny Yang Chi-Hsuan Chuang Hsuan Lin Wei-Ju Chen Chia-Ying Chen Trees-Juen Chuang Chien-Ying Lai Long-Yuan Li Scott C. Schuyler Frank Leigh Lu Yu-Chuan Liu Jean Lu Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells
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 <i>Zscan4s</i> 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	article
author	Po-Yu Lin Denny Yang Chi-Hsuan Chuang Hsuan Lin Wei-Ju Chen Chia-Ying Chen Trees-Juen Chuang Chien-Ying Lai Long-Yuan Li Scott C. Schuyler Frank Leigh Lu Yu-Chuan Liu Jean Lu
author_facet	Po-Yu Lin Denny Yang Chi-Hsuan Chuang Hsuan Lin Wei-Ju Chen Chia-Ying Chen Trees-Juen Chuang Chien-Ying Lai Long-Yuan Li Scott C. Schuyler Frank Leigh Lu Yu-Chuan Liu Jean Lu
author_sort	Po-Yu Lin
title	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_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_sort	comparative analyses of single-cell transcriptomic profiles between in vitro totipotent blastomere-like cells and in vivo early mouse embryonic cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8e094dcf1fb8434c986d0415f34f3a63
work_keys_str_mv	AT poyulin comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT dennyyang comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT chihsuanchuang comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT hsuanlin comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT weijuchen comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT chiayingchen comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT treesjuenchuang comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT chienyinglai comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT longyuanli comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT scottcschuyler comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT frankleighlu comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT yuchuanliu comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells AT jeanlu comparativeanalysesofsinglecelltranscriptomicprofilesbetweeninvitrototipotentblastomerelikecellsandinvivoearlymouseembryoniccells
_version_	1718412663767171072

Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells

Ejemplares similares