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July 27, 2021

Exposure to hypoxia causes stress erythropoiesis and downregulates immune response genes in spleen of mice

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.

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.

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.


Histological analyses of the spleen. a Spleen index were calculated by one-way ANOVA (P?=?0.02) and followed by LSD multiple comparison test (p=0.033, 0.007, 0.006, respectively). Spleen index and the body weight index were calculated as described in Methods. b RBC counts of mice were calculated on the normoxia group (D0) and the day 1 (D1), 3 (D3), 5 (D5), 7 (D7), 13 (D13) after exposure to hypoxia (one-way ANOVA followed by LSD multiple comparison test was used .P-value:*p﹤0.05and **p﹤0.01

This result was published in Frontiers in BMC Genomics with the title of “Exposure to hypoxia causes stress erythropoiesis and downregulates immune response genes in spleen of mice”.

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