Novel roles for CREG1 in hematopoiesis revealed by single-cell RNA sequencing.

Background: Hematopoiesis, the process of generating diverse blood cell lineages, is essential for maintaining organismal homeostasis and survival. CREG1 has been implicated in various cellular processes, including proliferation, differentiation, and senescence. However, its role in adult hematopoiesis and the development of specific blood cell lineages remains largely unknown.

Results: In this study, we utilized single-cell RNA sequencing (scRNA-seq) to investigate the function of CREG1 in hematopoietic development in adult zebrafish. Our analysis revealed significant alterations in cellular composition and gene expression profiles in kidney marrow of creg1-deficient zebrafish, particularly affecting B cell, T/NK cell, and erythroid cell development. The loss of CREG1 led to impaired endocytosis and lysosomal activity in lymphocytes, and inhibited differentiation of classical erythroid cells while promoting the development of immune-associated erythroid cells. These findings highlight a critical role for CREG1 in regulating hematopoietic lineage development, potentially through modulation of cell survival, endocytosis, and lysosomal function.

Conclusions: Our study expands the current understanding of CREG1's role in hematopoiesis and provides a foundation for future investigations into the specific molecular mechanisms by which CREG1 regulates hematopoietic lineage development and function.