Prediction of hub genes and key pathways associated with the radiation response of human hematopoietic stem/progenitor cells using integrated bioinformatics methods

Abstract

Hematopoietic stem cells (HSCs) are indispensable for the maintenance of the entire blood program through cytokine response. However, HSCs have high radiosensitivity, which is often a problem during radiation therapy and nuclear accidents. Although our previous study has reported that the combination cytokine treatment (interleukin-3, stem cell factor, and thrombopoietin) improves the survival of human hematopoietic stem/progenitor cells (HSPCs) after radiation, the mechanism by which cytokines contribute to the survival of HSPCs is largely unclear. To address this issue, the present study characterized the effect of cytokines on the radiation-induced gene expression profile of human CD34+ HSPCs and explored the hub genes that play key pathways associated with the radiation response using a cDNA microarray, a protein–protein interaction-MCODE module analysis and Cytohubba plugin tool in Cytoscape. This study identified 2,733 differentially expressed genes (DEGs) and five hub genes (TOP2A, EZH2, HSPA8, GART, HDAC1) in response to radiation in only the presence of cytokines. Furthermore, functional enrichment analysis found that hub genes and top DEGs based on fold change were enriched in the chromosome organization and organelle organization. The present findings may help predict the radiation response and improve our understanding of this response of human HSPCs.

Ferroptosis, Inflammation, and Microbiome Alterations in the Intestine in the Göttingen Minipig Model of Hematopoietic-Acute Radiation Syndrome

“…Local and systemic inflammation are hallmarks of radiation exposure, even at sublethal exposures [1,9,32,34,35,58]. The generation of acute inflammatory responses that we observed following total body irradiation exposure is likely due to a combination of local cellular injury/death and the loss of hematopoietic cells, triggering the upregulation of cytokines to induce the cycling/development of hematopoietic stem and progenitor cells [32,34,35,59,60]. A sustained upregulation of p21/waf1 and pro-inflammatory cytokines can occur through radiation-induced accelerated senescence, causing the activation of the senescence-associated secretory phenotype [61,62].…”

“…(1) sham + vehicle (anesthesia only); (2) radiation + vehicle; (3) radiation + captopril. While under anesthesia (telazol/xylazine, 4.4-2 mg/kg), the swine were positioned in a Panepinto sling and exposed bilaterally to a target total-body dose of 1.79-1.80 Gy 60 Co irradiation delivered at a dose rate of 0.485-0.502 Gy/min, as previously described [18,35,79,80]. A dose of 1.79 Gy was used for three studies with 35-day endpoints and 1.80 Gy was used for one study with a 6-day endpoint.…”