3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment

Physical signals provided by the extracellular matrix (ECM) are key microenvironmental parameters for the fate decision of hematopoietic stem and progenitor cells (HSPC) in bone marrow. Insights into cell-ECM interactions are critical for advancing HSC-based tissue engineering. Herein, we employed c...

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Main Authors: Pan Zhang, Linmu Xu, Jingsong Gao, Guangkui Xu, Yanping Song, Guang Li, Jingjing Ren, Yunjie Zhang, Cheng Yang, Yu Zhang, Ruiheng Xie, Nu Zhang, Hui Yang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2022-04-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X21004084
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author Pan Zhang
Linmu Xu
Jingsong Gao
Guangkui Xu
Yanping Song
Guang Li
Jingjing Ren
Yunjie Zhang
Cheng Yang
Yu Zhang
Ruiheng Xie
Nu Zhang
Hui Yang
author_facet Pan Zhang
Linmu Xu
Jingsong Gao
Guangkui Xu
Yanping Song
Guang Li
Jingjing Ren
Yunjie Zhang
Cheng Yang
Yu Zhang
Ruiheng Xie
Nu Zhang
Hui Yang
author_sort Pan Zhang
collection DOAJ
description Physical signals provided by the extracellular matrix (ECM) are key microenvironmental parameters for the fate decision of hematopoietic stem and progenitor cells (HSPC) in bone marrow. Insights into cell-ECM interactions are critical for advancing HSC-based tissue engineering. Herein, we employed collagen hydrogels and collagen-alginate hydrogels of defined stiffness to study the behaviors of hematopoietic progenitor cells (HPCs). Three-dimensional (3D) collagen hydrogels with a stiffness of 45 Pa were found to promote HPC maintenance and colony formation of monocyte/macrophage progenitors. Using single-cell RNA sequencing (scRNA-seq), we also characterized the comprehensive transcriptional profiles of cells randomly selected from two-dimensional (2D) and 3D hydrogels. A distinct maturation trajectory from HPCs into macrophages within the 3D microenvironment was revealed by these results. 3D-derived macrophages expressed high levels of various cytokines and chemokines, such as Saa3, Cxcl2, Socs3 and Tnf. Furthermore, enhanced communication between 3D-macrophages and other hematopoietic clusters based on ligand-repair interactions was demonstrated through bioinformatic analyses. Our research underlines the regulatory role of matrix-dimensionality in HPC differentiation and therefore probably be applied to the generation of specialized macrophages.
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spelling doaj.art-f5c8d6db82a34a58bf2f58abfab572c32024-04-16T20:20:36ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-04-01102552683D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitmentPan Zhang0Linmu Xu1Jingsong Gao2Guangkui Xu3Yanping Song4Guang Li5Jingjing Ren6Yunjie Zhang7Cheng Yang8Yu Zhang9Ruiheng Xie10Nu Zhang11Hui Yang12School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China; Research Center of Special Environmental Biomechanics & Medical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, ChinaSchool of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China; Research Center of Special Environmental Biomechanics & Medical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, ChinaSchool of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China; Research Center of Special Environmental Biomechanics & Medical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, ChinaSchool of Aerospace Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, ChinaInstitute of Hematology, Xi'an Central Hospital, Xi'an, Shaanxi, 710003, ChinaInstitute of Hematology, Xi'an Central Hospital, Xi'an, Shaanxi, 710003, ChinaInstitute of Hematology, Xi'an Central Hospital, Xi'an, Shaanxi, 710003, ChinaInstitute of Hematology, Xi'an Central Hospital, Xi'an, Shaanxi, 710003, ChinaSchool of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China; Research Center of Special Environmental Biomechanics & Medical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, ChinaSchool of Computer Science, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, ChinaDepartment of Computer and Information Science, University of Delaware, Newark, DE, USASchool of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China; Research Center of Special Environmental Biomechanics & Medical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, ChinaSchool of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China; Research Center of Special Environmental Biomechanics & Medical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China; Corresponding author. Northwestern Polytechnical University, #127 West Youyi Road, Xi'an, Shaanxi 710072, China.Physical signals provided by the extracellular matrix (ECM) are key microenvironmental parameters for the fate decision of hematopoietic stem and progenitor cells (HSPC) in bone marrow. Insights into cell-ECM interactions are critical for advancing HSC-based tissue engineering. Herein, we employed collagen hydrogels and collagen-alginate hydrogels of defined stiffness to study the behaviors of hematopoietic progenitor cells (HPCs). Three-dimensional (3D) collagen hydrogels with a stiffness of 45 Pa were found to promote HPC maintenance and colony formation of monocyte/macrophage progenitors. Using single-cell RNA sequencing (scRNA-seq), we also characterized the comprehensive transcriptional profiles of cells randomly selected from two-dimensional (2D) and 3D hydrogels. A distinct maturation trajectory from HPCs into macrophages within the 3D microenvironment was revealed by these results. 3D-derived macrophages expressed high levels of various cytokines and chemokines, such as Saa3, Cxcl2, Socs3 and Tnf. Furthermore, enhanced communication between 3D-macrophages and other hematopoietic clusters based on ligand-repair interactions was demonstrated through bioinformatic analyses. Our research underlines the regulatory role of matrix-dimensionality in HPC differentiation and therefore probably be applied to the generation of specialized macrophages.http://www.sciencedirect.com/science/article/pii/S2452199X21004084Hematopoietic progenitor cellsCollagenMatrix-dimensionalityMacrophages
spellingShingle Pan Zhang
Linmu Xu
Jingsong Gao
Guangkui Xu
Yanping Song
Guang Li
Jingjing Ren
Yunjie Zhang
Cheng Yang
Yu Zhang
Ruiheng Xie
Nu Zhang
Hui Yang
3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment
Bioactive Materials
Hematopoietic progenitor cells
Collagen
Matrix-dimensionality
Macrophages
title 3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment
title_full 3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment
title_fullStr 3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment
title_full_unstemmed 3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment
title_short 3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment
title_sort 3d collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment
topic Hematopoietic progenitor cells
Collagen
Matrix-dimensionality
Macrophages
url http://www.sciencedirect.com/science/article/pii/S2452199X21004084
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