Haijing Wang1,2,3,4, Daoxin Liu1,3,4, Pengfei Song1,3,4, Feng Jiang1,3,4, Xiangwen Chi1,3, Tongzuo Zhang5,6. 1. Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810001, Qinghai, China. 2. Medical College of Qinghai University, Xining, 810016, Qinghai, China. 3. Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, 810008, Qinghai, China. 4. University of Chinese Academy of Sciences, Beijing, 100049, China. 5. Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810001, Qinghai, China. zhangtz@nwipb.cas.cn. 6. Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, 810008, Qinghai, China. zhangtz@nwipb.cas.cn.
Abstract
BACKGROUND: The spleen is the largest secondary lymphoid organ and the main site where stress erythropoiesis occurs. It is known that hypoxia triggers the expansion of erythroid progenitors; however, its effects on splenic gene expression are still unclear. Here, we examined splenic global gene expression patterns by time-series RNA-seq after exposing mice to hypoxia for 0, 1, 3, 5, 7 and 13 days. RESULTS: Morphological analysis showed that on the 3rd day there was a significant increase in the spleen index and in the proliferation of erythroid progenitors. RNA-sequencing analysis revealed that the overall expression of genes decreased with increased hypoxic exposure. Compared with the control group, 1380, 3430, 4396, 3026, and 1636 genes were differentially expressed on days 1, 3, 5, 7 and 13, respectively. Clustering analysis of the intersection of differentially expressed genes pointed to 739 genes, 628 of which were upregulated, and GO analysis revealed a significant enrichment for cell proliferation. Enriched GO terms of downregulated genes were associated with immune cell activation. Expression of Gata1, Tal1 and Klf1 was significantly altered during stress erythropoiesis. Furthermore, expression of genes involved in the immune response was inhibited, and NK cells decreased. CONCLUSIONS: The spleen of mice conquer hypoxia exposure in two ways. Stress erythropoiesis regulated by three transcription factors and genes in immune response were downregulated. These findings expand our knowledge of splenic transcriptional changes during hypoxia.
BACKGROUND: The spleen is the largest secondary lymphoid organ and the main site where stress erythropoiesis occurs. It is known that hypoxia triggers the expansion of erythroid progenitors; however, its effects on splenic gene expression are still unclear. Here, we examined splenic global gene expression patterns by time-series RNA-seq after exposing mice to hypoxia for 0, 1, 3, 5, 7 and 13 days. RESULTS: Morphological analysis showed that on the 3rd day there was a significant increase in the spleen index and in the proliferation of erythroid progenitors. RNA-sequencing analysis revealed that the overall expression of genes decreased with increased hypoxic exposure. Compared with the control group, 1380, 3430, 4396, 3026, and 1636 genes were differentially expressed on days 1, 3, 5, 7 and 13, respectively. Clustering analysis of the intersection of differentially expressed genes pointed to 739 genes, 628 of which were upregulated, and GO analysis revealed a significant enrichment for cell proliferation. Enriched GO terms of downregulated genes were associated with immune cell activation. Expression of Gata1, Tal1 and Klf1 was significantly altered during stress erythropoiesis. Furthermore, expression of genes involved in the immune response was inhibited, and NK cells decreased. CONCLUSIONS: The spleen of mice conquer hypoxia exposure in two ways. Stress erythropoiesis regulated by three transcription factors and genes in immune response were downregulated. These findings expand our knowledge of splenic transcriptional changes during hypoxia.
Authors: Graeme M Purdy; Marina A James; Jordan L Rees; Peter Ondrus; Jamie L Keess; Trevor A Day; Craig D Steinback Journal: J Appl Physiol (1985) Date: 2018-11-21
Authors: Christopher N Inra; Bo O Zhou; Melih Acar; Malea M Murphy; James Richardson; Zhiyu Zhao; Sean J Morrison Journal: Nature Date: 2015-11-16 Impact factor: 49.962