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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Autores principales: 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
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Publicado: KeAi Communications Co., Ltd. 2022
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Acceso en línea:https://doaj.org/article/f5c8d6db82a34a58bf2f58abfab572c3
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spelling oai:doaj.org-article:f5c8d6db82a34a58bf2f58abfab572c32021-11-28T04:35:22Z3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment2452-199X10.1016/j.bioactmat.2021.08.032https://doaj.org/article/f5c8d6db82a34a58bf2f58abfab572c32022-04-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21004084https://doaj.org/toc/2452-199XPhysical 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.Pan ZhangLinmu XuJingsong GaoGuangkui XuYanping SongGuang LiJingjing RenYunjie ZhangCheng YangYu ZhangRuiheng XieNu ZhangHui YangKeAi Communications Co., Ltd.articleHematopoietic progenitor cellsCollagenMatrix-dimensionalityMacrophagesMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 10, Iss , Pp 255-268 (2022)
institution DOAJ
collection DOAJ
language EN
topic Hematopoietic progenitor cells
Collagen
Matrix-dimensionality
Macrophages
Materials of engineering and construction. Mechanics of materials
TA401-492
Biology (General)
QH301-705.5
spellingShingle Hematopoietic progenitor cells
Collagen
Matrix-dimensionality
Macrophages
Materials of engineering and construction. Mechanics of materials
TA401-492
Biology (General)
QH301-705.5
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
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.
format article
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
title 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_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_sort 3d collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment
publisher KeAi Communications Co., Ltd.
publishDate 2022
url https://doaj.org/article/f5c8d6db82a34a58bf2f58abfab572c3
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