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

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.