Transcriptome and network changes in climbers at extreme altitudes
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Transcriptome and network changes in climbers at extreme altitudes. / Chen, Fang; Zhang, Wei; Liang, Yu; Huang, Jialiang; Li, Kui; Green, Christopher D.; Liu, Jiancheng; Zhang, Guojie; Zhou, Bing; Yi, Xin; Wang, Wei; Liu, Hang; Xu, Xiaohong; Shen, Feng; Qu, Ning; Wang, Yading; Gao, Guoyi; San, A.; JiangBai, LuoSang; Sang, Hua; Fang, Xiangdong; Kristiansen, Karsten; Yang, Huanming; Wang, Jun; Han, Jing-Dong J.; Wang, Jian.
In: P L o S One, Vol. 7, No. 2, 2012, p. e31645-e31645.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Transcriptome and network changes in climbers at extreme altitudes
AU - Chen, Fang
AU - Zhang, Wei
AU - Liang, Yu
AU - Huang, Jialiang
AU - Li, Kui
AU - Green, Christopher D.
AU - Liu, Jiancheng
AU - Zhang, Guojie
AU - Zhou, Bing
AU - Yi, Xin
AU - Wang, Wei
AU - Liu, Hang
AU - Xu, Xiaohong
AU - Shen, Feng
AU - Qu, Ning
AU - Wang, Yading
AU - Gao, Guoyi
AU - San, A.
AU - JiangBai, LuoSang
AU - Sang, Hua
AU - Fang, Xiangdong
AU - Kristiansen, Karsten
AU - Yang, Huanming
AU - Wang, Jun
AU - Han, Jing-Dong J.
AU - Wang, Jian
PY - 2012
Y1 - 2012
N2 - Extreme altitude can induce a range of cellular and systemic responses. Although it is known that hypoxia underlies the major changes and that the physiological responses include hemodynamic changes and erythropoiesis, the molecular mechanisms and signaling pathways mediating such changes are largely unknown. To obtain a more complete picture of the transcriptional regulatory landscape and networks involved in extreme altitude response, we followed four climbers on an expedition up Mount Xixiabangma (8,012 m), and collected blood samples at four stages during the climb for mRNA and miRNA expression assays. By analyzing dynamic changes of gene networks in response to extreme altitudes, we uncovered a highly modular network with 7 modules of various functions that changed in response to extreme altitudes. The erythrocyte differentiation module is the most prominently up-regulated, reflecting increased erythrocyte differentiation from hematopoietic stem cells, probably at the expense of differentiation into other cell lineages. These changes are accompanied by coordinated down-regulation of general translation. Network topology and flow analyses also uncovered regulators known to modulate hypoxia responses and erythrocyte development, as well as unknown regulators, such as the OCT4 gene, an important regulator in stem cells and assumed to only function in stem cells. We predicted computationally and validated experimentally that increased OCT4 expression at extreme altitude can directly elevate the expression of hemoglobin genes. Our approach established a new framework for analyzing the transcriptional regulatory network from a very limited number of samples.
AB - Extreme altitude can induce a range of cellular and systemic responses. Although it is known that hypoxia underlies the major changes and that the physiological responses include hemodynamic changes and erythropoiesis, the molecular mechanisms and signaling pathways mediating such changes are largely unknown. To obtain a more complete picture of the transcriptional regulatory landscape and networks involved in extreme altitude response, we followed four climbers on an expedition up Mount Xixiabangma (8,012 m), and collected blood samples at four stages during the climb for mRNA and miRNA expression assays. By analyzing dynamic changes of gene networks in response to extreme altitudes, we uncovered a highly modular network with 7 modules of various functions that changed in response to extreme altitudes. The erythrocyte differentiation module is the most prominently up-regulated, reflecting increased erythrocyte differentiation from hematopoietic stem cells, probably at the expense of differentiation into other cell lineages. These changes are accompanied by coordinated down-regulation of general translation. Network topology and flow analyses also uncovered regulators known to modulate hypoxia responses and erythrocyte development, as well as unknown regulators, such as the OCT4 gene, an important regulator in stem cells and assumed to only function in stem cells. We predicted computationally and validated experimentally that increased OCT4 expression at extreme altitude can directly elevate the expression of hemoglobin genes. Our approach established a new framework for analyzing the transcriptional regulatory network from a very limited number of samples.
U2 - 10.1371/journal.pone.0031645
DO - 10.1371/journal.pone.0031645
M3 - Journal article
C2 - 22393366
VL - 7
SP - e31645-e31645
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 2
ER -
ID: 40905530