2. Academic Validation
  3. A single-cell hematopoietic microenvironmental atlas reveals progressive maturation of bone marrow vascular niche

A single-cell hematopoietic microenvironmental atlas reveals progressive maturation of bone marrow vascular niche

  • Cell Regen. 2025 Dec 4;14(1):50. doi: 10.1186/s13619-025-00265-7.
Lan-Yue Ma # 1 2 3 4,  Zhao-Hua Deng # 1 2 3 4,  Ke Bai 5,  Yan-Mei Yu 1 2 3 4,  Yin Huang 5,  Rong-Rong Gao 1 2 3 4,  Yu-Yan Li 1 2 3 4,  Xiao-Ling Li 1 3 4,  Jia-Xin Yang 5,  Ya-Hai Shu 1,  Jinjin Ma 5 6,  Yang Liu 7,  Qi Chen 8 9 10
Affiliations

Affiliations

  • 1 Center for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 101408, China.
  • 3 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
  • 4 Guangzhou Medical University, Guangzhou, 511436, China.
  • 5 The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, 510006, China.
  • 6 The Institute of Future Health, South China of Technology, Guangzhou International Campus, Guangzhou, 511442, China.
  • 7 The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, 510006, China. [email protected].
  • 8 Center for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. [email protected].
  • 9 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. [email protected].
  • 10 Guangzhou Medical University, Guangzhou, 511436, China. [email protected].
  • # Contributed equally.
PMID: 41339619 DOI: 10.1186/s13619-025-00265-7
Abstract

The interaction between hematopoietic stem and progenitor cell (HSPC) and its vascular niche is essential for supporting the homeostasis and reconstitution of hematopoietic system in adult bone marrow (BM), but a comprehensive atlas covering this HSPC-vascular niche crosstalk in multiple developmental stages and species is lacking. Here, we integrated single-cell transcriptomic data of HSPC and its vascular niches from fetal liver until aged BM, covering two species, two organs, and six developmental time points. Comparative analyses revealed dramatic differences in the gene expression, enriched pathway, and cell-cell communication between human fetal and adult BM. Notably, many of these differences were conserved between humans and mice. Multi-timepoint profiling of murine BM vascular niches revealed a stepwise maturation of gene expression, including critical niche factors such as SCF and CXCL12. Furthermore, analysis of this dynamic vascular niche atlas highlighted organ-specific features between fetal liver and BM niches, significant transcriptional changes in aged BM endothelial cells, and identified midkine as a previously unknown niche factor. Functional validation showed that transplanting HSPC into midkine knockout mice or treating with a midkine inhibitor (iMDK) enhanced hematopoietic reconstitution. In contrast, recombinant midkine suppressed HSPC differentiation. Together, our work presents a cross-species and multi-stage atlas of HSPC-vascular niche interactions, offering valuable insights into the dynamic changes of vascular niche through lifelong HSPC development and a platform to identify unknown niche factors.

Keywords

Hematopoietic microenvironment; Midkine; Niche atlas; scRNA-seq.

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