The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Examining Post-Transcriptional Regulation of Skeletal Muscle Satellite Cell Homeostasis, Activation and Fate Determination

Skeletal muscle is essential for respiration, mobility, reproduction and metabolism. Deficits in muscle function due to disease, injury or age reduce both quality of life and lifespan. Muscles are long-lived tissues that require maintenance to retain functional integrity throughout the life of an organism. Satellite cells are the adult stem cells responsible for muscle repair and maintenance. Upon myotrauma, satellite cells re-enter the cell cycle, proliferate, and terminally differentiate to repair the muscle. In uninjured tissue, satellite cells are quiescent and infrequently proceed through myogenesis for muscle maintenance. The molecular mechanisms that regulate satellite cell quiescence and activation are poorly defined. Additionally, no comprehensive studies have determined when satellite cells attain quiescence in the adult tissue or whether satellite cells in different muscle acquire quiescence at distinct times. Here, I investigate when satellite cells attain quiescence. Using Pax7ICreERT2; R26RtdTomato mice to fluorescently label satellite cells, I determine that hindlimb muscles establish quiescence by 12 weeks of age; whereas, extraocular muscles fail to establish quiescence by 27 weeks. Additionally, I find that satellite cell contribution to adult muscle is greater than was assumed based on the low number of cycling satellite cells in uninjured muscle. Furthermore, I show that satellite cells contribution varies by both age and muscle group. By comparing genome-wide expression profiles of quiescent and activating satellite cells, I identify RNA post-transcriptional regulation via RNA binding proteins as a regulatory mechanism of satellite cell activation. Specifically, I investigate the CELF family of RNA binding proteins. I find that CELF1/2/4 targets are enriched in genes downregulated during satellite cell activation. microRNAs that regulate satellite cell fate share targets with CELF1/2/4 during satellite cell activation. Additionally, CELF1/2/4 targets transcripts in key regulatory pathways of satellite cell activation, including p38 MAPK. I further examined gene expression profiles of aged satellite cells and identify elevated expression of genes downregulated during satellite cell activation, particularly RNA splicing and processing genes, that likely contribute to the impaired activation, self renewal and proliferation of aged satellite cells. Together, these data suggest the RNA post-transcriptional regulation of gene expression as a key mechanism mediating satellite cell activation

A role for RNA post-transcriptional regulation in satellite cell activation

Abstract Background Satellite cells are resident skeletal muscle stem cells responsible for muscle maintenance and repair. In resting muscle, satellite cells are maintained in a quiescent state. Satellite cell activation induces the myogenic commitment factor, MyoD, and cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent satellite cell to a transit-amplifying myoblast is poorly understood. Methods Satellite cells isolated by FACS from uninjured skeletal muscle and 12 h post-muscle injury from wild type and Syndecan-4 null mice were probed using Affymetrix 430v2 gene chips and analyzed by Spotfiretm and Ingenuity Pathway analysis to identify gene expression changes and networks associated with satellite cell activation, respectively. Additional analyses of target genes identify miRNAs exhibiting dynamic changes in expression during satellite cell activation. The function of the miRNAs was assessed using miRIDIAN hairpin inhibitors. Results An unbiased gene expression screen identified over 4,000 genes differentially expressed in satellite cells in vivo within 12 h following muscle damage and more than 50% of these decrease dramatically. RNA binding proteins and genes involved in post-transcriptional regulation were significantly over-represented whereas splicing factors were preferentially downregulated and mRNA stability genes preferentially upregulated. Furthermore, six computationally identified miRNAs demonstrated novel expression through muscle regeneration and in satellite cells. Three of the six miRNAs were found to regulate satellite cell fate. Conclusions The quiescent satellite cell is actively maintained in a state poised to activate in response to external signals. Satellite cell activation appears to be regulated by post-transcriptional gene regulation

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies