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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KeAi Communications Co., Ltd.
2022
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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) |
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DOAJ |
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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 |
work_keys_str_mv |
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