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CD34+ cell atlas of main organs implicates its impact on fibrosis

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Abstract

Rationale

CD34+ cells are believed being progenitors that may be used to treat cardiovascular disease. However, the exact identity and the role of CD34+ cells in physiological and pathological conditions remain unclear.

Methods

We performed single-cell RNA sequencing analysis to provide a cell atlas of normal tissue/organ and pathological conditions. Furthermore, a genetic lineage tracing mouse model was used to investigate the role of CD34+ cells in angiogenesis and organ fibrosis.

Results

Single-cell RNA sequencing analysis revealed a heterogeneous population of CD34+ cells in both physiological and pathological conditions. Using a genetic lineage tracing mouse model, we showed that CD34+ cells not only acquired endothelial cell fate involved in angiogenesis, but also, CD34+ cells expressing Pi16 may transform into myofibroblast and thus participate in organ fibrosis.

Conclusion

A heterogeneous CD34+ cells serve as a contributor not only to endothelial regeneration but also a wound healing response that may provide therapeutic insights into fibrosis.

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Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files, or are available from the corresponding author upon reasonable request.

Abbreviations

CD:

Cluster of differentiation

EPC:

Endothelial progenitor cell

ScRNA-seq:

Single cell RNA sequencing

MSC:

Mesenchymal stem cell

CCA:

Canonical correlation analysis

t-SNE:

T-distributed stochastic neighbor embedding

α-SMA:

Alpha smooth muscle actin

PDGFR:

Platelet-derived growth factor receptor

AngII:

Angiotensin II

UUO:

Unilateral ureteral obstruction

BMT:

Bone-marrow transplantation

EC:

Endothelial cell

UMAP:

Uniform manifold approximation and projection

IFN:

Interferon

ECM:

Extracellular matrix

CXCL:

C-X-C motif chemokine ligand

FGF:

Fibroblast growth factor

TGF:

Transforming growth factor

IGF:

Insulin-like growth factor

CTGF:

Connective tissue growth factor

TAC:

Transverse aortic constriction

CCL:

CC chemokine ligand

VEGF:

Vascular endothelial growth factor

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Acknowledgements

This work was supported by Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare and Alibaba Cloud. We are also grateful to the Core Facility Platform of Zhejiang University School of Medicine for technical assistance.

Funding

National Natural Science Foundation of China 31830039 (Q. Xu), 82030008 (Q. Xu). National Natural Science Foundation of China 82170489 and the Natural Science Foundation of Zhejiang Province (LR22H020001) (T. Chen). National Natural Science Foundation of China 81600339 and the Natural Science Foundation of Zhejiang Province LY19H020009 (X. Pu).

Author information

Author notes

  1. Xiangyuan Pu, Pengwei Zhu and Xuhao Zhou contributed equally.

Authors and Affiliations

  1. Department of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Hangzhou, China

    Xiangyuan Pu, Pengwei Zhu, Xuhao Zhou, Hong Wu, Luping Du, Hui Gong, Xiaotong Sun, Ting Chen, Jianhua Zhu & Qingbo Xu

  2. Department of Vascular Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Yangyan He & Hongkun Zhang

  3. Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou, China

    Ting Chen

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  1. Xiangyuan Pu
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Contributions

Conceptualization: QX and HZ. Methodology: XP, PZ, XZ, and YH. Investigation: XP, PZ, XZ, HW, LD, HG, XS, and TC. Visualization: XP, PZ, and XZ. Supervision: QX, JZ, and HZ. Writing—original draft: XP, PZ, XZ, and QX. Writing—review and editing: YH, HW, LD, HG, XS, JZ, and TC. XP, TC, and QX acquired funding. All authors contributed to the article.

Corresponding authors

Correspondence to Jianhua Zhu, Qingbo Xu or Hongkun Zhang.

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The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Human sample procedures had local ethical approval. All mice experiments were approved by the Institutional Animal Care and Use Committee of Zhejiang University School of Medicine.

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Pu, X., Zhu, P., Zhou, X. et al. CD34+ cell atlas of main organs implicates its impact on fibrosis. Cell. Mol. Life Sci. 79, 576 (2022). https://doi.org/10.1007/s00018-022-04606-6

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