Bone marrow-derived non-transformed murine macrophages with an unlimited self-renewing ability

GSE142619 Bone marrow-derived non-transformed murine macrophages with an unlimited self-renewing ability: Contributors : Hesham Nasser ; Partho Adhikary ; Amira Abdel-Daim ; Osamu Noyori ; Ryusho Kariya ; Seiji Okada ; Wenjuan Ma ; Masaya Baba ; Hitoshi Takizawa ; Mariko Yamane ; Hitoshi Niwa ; Shinya Suzu

Series Type : Expression profiling by array

Organism : Mus musculus

Tissue macrophages derive from bone marrow monocytes, and recent studies using mice have revealed that they also derive from yolk sac precursors or fetal liver monocytes. However, embryo-derived macrophages are supposed to be more important to maintain tissue macrophage pool because they can self-renew. Here, we show that adult bone marrow-derived macrophages (MDM) also retain the ability of self-renewal. Where they were readily obtained by a long-term culture: mouse bone marrow cells were cultured with macrophage colony-stimulating factor (M-CSF). After several passages, most MDM died owing to their limited life span with survival and expansion of self-renewing macrophages resided in a small fraction. Self-renewing macrophages were not tumorigenic, but proliferate for a long period in almost unlimited numbers. Despite being distinct from MDM, they were phenotypically and functionally differentiated macrophages, and could differentiate into dendritic cells or osteoclasts. Moreover, Krüppel-like Factor 2 (KLF2) involved in self-renewal of embryonic stem cells, was markedly up-regulated by M-CSF-stimulation in self-renewing macrophages, which was accompanied with a gradual down-regulation of MafB, a suppressor of KLF2 expression. Importantly, knockdown of KLF2 as well as c-Myc caused cell cycle arrest, apoptosis, and diminished cell growth. Our culture method results suggest the presence of precursor(s) for self-renewing macrophages in adult bone marrow that can be used to describe discrepancy of adult- and embryo-derived macrophages.
Microarray data from both monocyte-derived and bone marrow-derived mouse macrophages are used to detail the global gene expression profile underlying phenotype, function and self-renewal capacity in order to unravel difference/similarity in phenotype/function and mechanism/degree of self-renewal between the two distinct macrophages.