CDK14 is a critical regulator of haematopoietic stem and progenitor cell maintenance and post-transplantation proliferation

  • FEBS J. 2026 May 4. doi: 10.1111/febs.70562.
Ya-Fei Li  1 ,  Tian-Jing Li  1 ,  Yin Huang  1 ,  Ke Bai  1 ,  Rong-Rong Gao  2  3  4  5 ,  Jia-Xin Yang  1 ,  Lan-Yue Ma  2  3  4  5 ,  Yan-Mei Yu  2  3  4  5 ,  Jinjin Ma  6 ,  Qi Chen  2  3  4  5 ,  Yang Liu  1
Affiliations
  • 1. The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, China.
  • 2. Center for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China.
  • 3. University of Chinese Academy of Sciences, Beijing, China.
  • 4. Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • 5. Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
  • 6. The Institute of Future Health, South China University of Technology, Guangzhou International Campus, Guangzhou, China.
PMID: 42080702 DOI: 10.1111/febs.70562
Abstract

Cyclin-dependent kinase (CDK) 14 is involved in Wnt signalling, tissue repair, and tumourigenesis, but its function in haematopoiesis remains unexplored. Here, we found that CDK14 was necessary to maintain physiological haematopoiesis under steady-state and haematopoietic reconstitution after transplantation using genetic and pharmacological interventions. By utilising CDK14 knockout and haematopoietic-deletion (CDK14∆HC) mouse models, in combination with the selective CDK14 Inhibitor FMF-04-159-2, we showed that ablation of CDK14 resulted in diminished haematopoietic stem and progenitor cells (HSPCs), and disrupted the proportion of mature haematopoietic cells. Single-cell RNA Sequencing analysis of bone marrow from CDK14∆HC mice revealed impaired cell cycle progression, perturbed HSPC proportion, and altered niche-HSPC interactions. Furthermore, genetic and pharmacological ablation of CDK14 markedly decreased HSPC proliferation after transplantation in vivo and reduced colony formation in vitro. These findings identify CDK14 as a critical regulator of haematopoietic homeostasis and highlight its essential role in supporting HSPC function under stress conditions.

Keywords
cell cycle; cell interaction; haematopoiesis; haematopoietic stem and progenitor cell; microenvironment.
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