Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells

The generation of blood cells in a significant amount for clinical uses is still challenging. Human pluripotent stem cells-derived hemopoietic cells (hPSC-HCs) are a promising cell source to generate blood cells. Previously, it has been shown that the attached substrates are crucial in the maintenan...

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Autores principales:	Jiao Lin, Jiahui Zeng, Wencui Sun, Kun Liu, Myagmartsend Enkhbat, Danying Yi, Javad Harati, Jiaxin Liu, Peter Kingshott, Bo Chen, Feng Ma, Peng-Yuan Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	colloidal self-assembly artificial ECM pluripotent stem cells hematopoiesis blood cells focal adhesion Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ef18aa4f31bd4fafa2b2c2e8ac76fd9e
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spelling	oai:doaj.org-article:ef18aa4f31bd4fafa2b2c2e8ac76fd9e2021-11-16T07:39:17ZColloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells2296-634X10.3389/fcell.2021.771773https://doaj.org/article/ef18aa4f31bd4fafa2b2c2e8ac76fd9e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.771773/fullhttps://doaj.org/toc/2296-634XThe generation of blood cells in a significant amount for clinical uses is still challenging. Human pluripotent stem cells-derived hemopoietic cells (hPSC-HCs) are a promising cell source to generate blood cells. Previously, it has been shown that the attached substrates are crucial in the maintenance or differentiation of hPSCs. In this study, a new family of artificial extracellular matrix (ECM) called colloidal self-assembled patterns (cSAPs: #1–#5) was used for the expansion of mouse and human PSCs. The optimized cSAP (i.e., #4 and #5) was selected for subsequent hemopoietic differentiation of human embryonic stem cells (hESCs). Results showed that the hematopoietic potential of hESCs was enhanced approx 3–4 folds on cSAP #5 compared to the flat control. The cell population of hematopoietic progenitors (i.e., CD34+CD43+ cells) and erythroid progenitors (i.e., CD71+GPA+ cells) were enhanced 4 folds at day 8 and 3 folds at day 14. RNA sequencing analysis of cSAP-derived hESCs showed that there were 300 genes up-regulated and 627 genes down-regulated compared to the flat control. The enriched signaling pathways, including up-regulation (i.e., Toll-like receptor, HIF-1a, and Notch) or down-regulation (i.e., FAs, MAPK, JAK/STAT, and TGF-β) were classic in the maintenance of hESC phenotype Real time PCR confirmed that the expression of focal adhesion (PTK2, VCL, and CXCL14) and MAPK signaling (CAV1) related genes was down-regulated 2-3 folds compared to the flat control. Altogether, cSAP enhances the pluripotency and the hematopoietic potential of hESCs that subsequently generates more blood-like cells. This study reveals the potential of cSAPs on the expansion and early-stage blood cell lineage differentiation of hPSCs.Jiao LinJiahui ZengWencui SunKun LiuMyagmartsend EnkhbatDanying YiJavad HaratiJiaxin LiuPeter KingshottBo ChenFeng MaPeng-Yuan WangPeng-Yuan WangFrontiers Media S.A.articlecolloidal self-assemblyartificial ECMpluripotent stem cellshematopoiesisblood cellsfocal adhesionBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colloidal self-assembly artificial ECM pluripotent stem cells hematopoiesis blood cells focal adhesion Biology (General) QH301-705.5
spellingShingle	colloidal self-assembly artificial ECM pluripotent stem cells hematopoiesis blood cells focal adhesion Biology (General) QH301-705.5 Jiao Lin Jiahui Zeng Wencui Sun Kun Liu Myagmartsend Enkhbat Danying Yi Javad Harati Jiaxin Liu Peter Kingshott Bo Chen Feng Ma Peng-Yuan Wang Peng-Yuan Wang Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells
description	The generation of blood cells in a significant amount for clinical uses is still challenging. Human pluripotent stem cells-derived hemopoietic cells (hPSC-HCs) are a promising cell source to generate blood cells. Previously, it has been shown that the attached substrates are crucial in the maintenance or differentiation of hPSCs. In this study, a new family of artificial extracellular matrix (ECM) called colloidal self-assembled patterns (cSAPs: #1–#5) was used for the expansion of mouse and human PSCs. The optimized cSAP (i.e., #4 and #5) was selected for subsequent hemopoietic differentiation of human embryonic stem cells (hESCs). Results showed that the hematopoietic potential of hESCs was enhanced approx 3–4 folds on cSAP #5 compared to the flat control. The cell population of hematopoietic progenitors (i.e., CD34+CD43+ cells) and erythroid progenitors (i.e., CD71+GPA+ cells) were enhanced 4 folds at day 8 and 3 folds at day 14. RNA sequencing analysis of cSAP-derived hESCs showed that there were 300 genes up-regulated and 627 genes down-regulated compared to the flat control. The enriched signaling pathways, including up-regulation (i.e., Toll-like receptor, HIF-1a, and Notch) or down-regulation (i.e., FAs, MAPK, JAK/STAT, and TGF-β) were classic in the maintenance of hESC phenotype Real time PCR confirmed that the expression of focal adhesion (PTK2, VCL, and CXCL14) and MAPK signaling (CAV1) related genes was down-regulated 2-3 folds compared to the flat control. Altogether, cSAP enhances the pluripotency and the hematopoietic potential of hESCs that subsequently generates more blood-like cells. This study reveals the potential of cSAPs on the expansion and early-stage blood cell lineage differentiation of hPSCs.
format	article
author	Jiao Lin Jiahui Zeng Wencui Sun Kun Liu Myagmartsend Enkhbat Danying Yi Javad Harati Jiaxin Liu Peter Kingshott Bo Chen Feng Ma Peng-Yuan Wang Peng-Yuan Wang
author_facet	Jiao Lin Jiahui Zeng Wencui Sun Kun Liu Myagmartsend Enkhbat Danying Yi Javad Harati Jiaxin Liu Peter Kingshott Bo Chen Feng Ma Peng-Yuan Wang Peng-Yuan Wang
author_sort	Jiao Lin
title	Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells
title_short	Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells
title_full	Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells
title_fullStr	Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells
title_full_unstemmed	Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells
title_sort	colloidal self-assembled patterns maintain the pluripotency and promote the hemopoietic potential of human embryonic stem cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ef18aa4f31bd4fafa2b2c2e8ac76fd9e
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Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells

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