Critical Role of Ferritin-Mediated Iron Homeostasis in the Maintenance of Hematopoietic Stem Cells and Leukemia Stem Cells

Iron metabolism has emerged as a critical factor in cell viability, both in normal and pathological contexts. However, the intricate relationship between iron metabolism and the maintenance of adult stem cells and cancer stem cells remains incompletely understood. The ferritin complex, responsible for intracellular iron storage and buffering, plays a pivotal role in this process. Our research provides insights into the regulatory role of ferritin-mediated iron homeostasis in hematopoietic stem cells (HSCs). We generate the conditional deletion of ferritin heavy chain 1 (Fth1) in the hematopoietic system to determine the function of iron in HSCs. Fth1-deleted HSC and WT HSC were isolated from 2-month-old Fth1 deletion and WT mice (3-4 repetitions per set), and the bulk RNA-seq were performed. Index of the reference genome was built using Hisat2 v2.0.4 and paired-end clean reads were aligned to the reference genome GRCm38 using Hisat2 v2.0.4. HTSeq v0.9.1 was used to count the reads numbers mapped to each gene. And then FPKM of each gene was calculated based on the length of the gene and reads count mapped to this gene.