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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Main Authors: 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.771773/full
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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
collection DOAJ
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.
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spelling doaj.art-ef18aa4f31bd4fafa2b2c2e8ac76fd9e2022-12-21T20:39:55ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-11-01910.3389/fcell.2021.771773771773Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem CellsJiao Lin0Jiahui Zeng1Wencui Sun2Kun Liu3Myagmartsend Enkhbat4Danying Yi5Javad Harati6Jiaxin Liu7Peter Kingshott8Bo Chen9Feng Ma10Peng-Yuan Wang11Peng-Yuan Wang12Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaStem Cell Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Chengdu, ChinaStem Cell Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Chengdu, ChinaShenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaShenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaStem Cell Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Chengdu, ChinaShenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaStem Cell Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Chengdu, ChinaDepartment of Chemistry and Biotechnology, Swinburne University of Technology, Hawthorn, VIC, AustraliaStem Cell Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Chengdu, ChinaStem Cell Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Chengdu, ChinaShenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Chemistry and Biotechnology, Swinburne University of Technology, Hawthorn, VIC, AustraliaThe 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.771773/fullcolloidal self-assemblyartificial ECMpluripotent stem cellshematopoiesisblood cellsfocal adhesion
spellingShingle 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
Frontiers in Cell and Developmental Biology
colloidal self-assembly
artificial ECM
pluripotent stem cells
hematopoiesis
blood cells
focal adhesion
title 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_short 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
topic colloidal self-assembly
artificial ECM
pluripotent stem cells
hematopoiesis
blood cells
focal adhesion
url https://www.frontiersin.org/articles/10.3389/fcell.2021.771773/full
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