Non‐steady‐state hematopoiesis regulated by the C/EBPβ transcription factor

Abstract

Steady-state hematopoiesis responds to extracellular stimuli to meet changing demands and also to pathologically altered intracellular signaling. Granulocyte production increases following infection or in response to cytokine stimulation, and activation of the CCAAT/enhancer-binding protein β (C/EBPβ) transcription factor is required for such stress-induced granulopoiesis, whereas C/EBPα plays a critical role in maintaining steady-state granulopoiesis. Different roles of these C/EBP transcription factors in different modes of hematopoiesis are evolutionally conserved from zebrafish to humans. In addition to reactions against infections, C/EBPβ is responsible for cancer-driven myelopoiesis, which promotes cancer progression, at least in part, by abrogating the immune response in the cancer microenvironment. The BCR–ABL fusion protein activates emergency-specific pathway of granulopoiesis by upregulating C/EBPβ. This in turn causes chronic phase chronic myeloid leukemia, which is characterized by myeloid expansion. The C/EBPβ transcription factor also plays a role in other hematological malignancies of both myeloid and lymphoid lineage origin. Thus, elucidation of the upstream and downstream networks surrounding C/EBPβ will lead to the development of novel therapeutic strategies for diseases mediated by non-steady-state hematopoiesis.

Augmentation of iNOS expression in myeloid progenitor cells expedites neutrophil differentiation

“…65 to be increased in C/EBP--mediated emergency granulopoiesis in myeloid-derived suppressor cells (MDSCs). 66 In line with this, reports suggest iNOS is downstream to the C/EBP--mediated signaling in stress-induced granulopoiesis as shown in zebrafish. 67 The role of iNOS in stress-induced granulopoiesis could thus form a promising scope for future studies.…”

“…This correlates with our observation of decreased in vitro cytokine‐induced neutropoiesis in iNOS KO mice as compared to WT. Furthermore, iNOS may have a role in stress‐induced granulopoiesis, as iNOS expression was found to be increased in C/EBP‐β‐mediated emergency granulopoiesis in myeloid‐derived suppressor cells (MDSCs) . In line with this, reports suggest iNOS is downstream to the C/EBP‐β‐mediated signaling in stress‐induced granulopoiesis as shown in zebrafish .…”

Copper nanoparticle-induced ovarian injury, follicular atresia, apoptosis, and gene expression alterations in female rats

“…37 The transcription factor of the leucine zipper basic region CCAAT/enhancer-binding protein b (C/EBPB) is a member of the C/EBP family. [51][52][53][54] Evidence has indicated that C/EBPB regulates cell differentiation, survival, proliferation, and metabolic processes by inhibition or activation of the target genes. A recent study showed that cells underwent accelerated apoptosis in Cebpbdeficient mice.…”

Kras promotes myeloid differentiation through Wnt/β‐catenin signaling

“…26 The partial inhibition of CD11b expression by treatment with neutralizing anti-G-CSF antibody during DMSO-induced differentiation suggests that DMSO regulates the differentiation of HL-60 cells by several distinct pathways. 56,57 In summary, the present study showed that wild-type Kras regulates the differentiation of HL-60 cells via the Wnt/β-catenin signaling pathway. DMSO triggers Kras activation through the recruitment of Kras to the plasma membrane (1,2).…”

“…56 One dispensable activity may be C/EBPα activation of the C/EBPɛ gene, 56 with C/EBPα replaced by C/ EBPβ under stress conditions. 56,57 In summary, the present study showed that wild-type Kras regulates the differentiation of HL-60 cells via the Wnt/β-catenin signaling pathway. Accumulation of C/EBPα upregulates the expression of G-CSF receptor and stimulates mature granulopoiesis in HL-60 cells.…”