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

• Published in: Bioactive materials 2022-04, Vol.10, p.255-268
• Main Authors: Zhang, Pan, Xu, Linmu, Gao, Jingsong, Xu, Guangkui, Song, Yanping, Li, Guang, Ren, Jingjing, Zhang, Yunjie, Yang, Cheng, Zhang, Yu, Xie, Ruiheng, Zhang, Nu, Yang, Hui
• Format: Article
• Language: English
• Subjects: Collagen; Hematopoietic progenitor cells; Macrophages; Matrix-dimensionality
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2021.08.032

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. [Display omitted] •3D collagen hydrogels influenced the maintenance of hematopoietic progenitor cells.•3D matrices modulated the lineage specification of hematopoietic progenitors and promoted the formation of CFU-M colonies.•Single-cell RNA sequencing identified a cluster of specialized macrophages within a 3D microenvironment.