Global S&T Development Trend Analysis Platform of Resources and Environment
Over the past 18,000 years, the residence time and amount of soil carbon stored in the Ganges-Brahmaputra basin have been controlled by the intensity of Indian Summer Monsoon rainfall, with greater carbon destabilization during wetter, warmer conditions.
The storage of organic carbon in the terrestrial biosphere directly affects atmospheric concentrations of carbon dioxide over a wide range of timescales. Within the terrestrial biosphere, the magnitude of carbon storage can vary in response to environmental perturbations such as changing temperature or hydroclimate(1), potentially generating feedback on the atmospheric inventory of carbon dioxide. Although temperature controls the storage of soil organic carbon at mid and high latitudes(2,3), hydroclimate may be the dominant driver of soil carbon persistence in the tropics(4,5)
Regulatory T (T-reg) cells are required to control immune responses and maintain homeostasis, but are a significant barrier to antitumour immunity(1). Conversely, T-reg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of proinflammatory properties(2), can promote autoimmunity and/or facilitate more effective tumour immunity(3,4). A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective T-reg therapies for autoimmune disease and cancer. The availability of new functional genetic tools has enabled the possibility of systematic dissection of the gene regulatory programs that modulate Foxp3 expression. Here we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse T-reg cells and applied this technology to perform a targeted loss-of-function screen of around 500 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We identified several modulators of Foxp3 expression, including ubiquitin-specific peptidase 22 (Usp22) and ring finger protein 20 (Rnf20). Usp22, a member of the deubiquitination module of the SAGA chromatin-modifying complex, was revealed to be a positive regulator that stabilized Foxp3 expression
A CRISPR-based screening platform was used to identify previously uncharacterized genes that regulate the regulatory T cell-specific master transcription factor Foxp3, indicating that this screening method may be broadly applicable for the discovery of other genes involved in autoimmunity and immune responses to cancer.
