Hutcheson JD, Schlotter F, Creager MD, Li X, Pham T, Vyas P, Higashi H, Body SC, Aikawa M, Singh SA.
Elastogenesis correlates with pigment production in murine aortic valve leaflets. Frontiers in Cardiovascular Medicine. 2021;8 :533.
Tosic I, Heppler LN, Egusquiaguirre SP, Boehnke N, Correa S, Costa DF, Moore EAG, Pal S, Richardson DS, Ivanov AR, et al. Lipidome-based Targeting of STAT3-driven Breast Cancer Cells Using Poly-l-glutamic Acid-coated Layer-by-Layer Nanoparticles. Mol Cancer Ther. 2021;20 (4) :726-738.
Publisher's VersionAbstractThe oncogenic transcription factor STAT3 is aberrantly activated in 70% of breast cancers, including nearly all triple-negative breast cancers (TNBCs). Because STAT3 is difficult to target directly, we considered whether metabolic changes driven by activated STAT3 could provide a therapeutic opportunity. We found that STAT3 prominently modulated several lipid classes, with most profound effects on N-acyl taurine and arachidonic acid, both of which are involved in plasma membrane remodeling. To exploit these metabolic changes therapeutically, we screened a library of layer-by-layer (LbL) nanoparticles (NPs) differing in the surface layer that modulates interactivity with the cell membrane. We found that poly-l-glutamic acid (PLE)-coated NPs bind to STAT3-transformed breast cancer cells with 50% greater efficiency than to nontransformed cells, and the heightened PLE-NP binding to TNBC cells was attenuated by STAT3 inhibition. This effect was also observed in densely packed three-dimensional breast cancer organoids. As STAT3-transformed cells show greater resistance to cytotoxic agents, we evaluated whether enhanced targeted delivery via PLE-NPs would provide a therapeutic advantage. We found that cisplatin-loaded PLE-NPs induced apoptosis of STAT3-driven cells at lower doses compared with both unencapsulated cisplatin and cisplatin-loaded nontargeted NPs. In addition, because radiation is commonly used in breast cancer treatment, and may alter cellular lipid distribution, we analyzed its effect on PLE-NP-cell binding. Irradiation of cells enhanced the STAT3-targeting properties of PLE-NPs in a dose-dependent manner, suggesting potential synergies between these therapeutic modalities. These findings suggest that cellular lipid changes driven by activated STAT3 may be exploited therapeutically using unique LbL NPs.
Valcourt JR, Huang RE, Kundu S, Venkatasubramanian D, Kingston RE, Ramanathan S.
Modulating mesendoderm competence during human germ layer differentiation. Cell reports. 2021;37 (6) :109990.
Harris JM, Wang AY-D, Arlotta P.
Optogenetic axon guidance in embryonic zebrafish. STAR Protocols. 2021;2 (4) :100947.
Publisher's VersionAbstractSummary Axons form the long-range connections of biological neuronal networks, which are built through the developmental process of axon guidance. Here, we describe a protocol to precisely and non-invasively control axonal growth trajectories in live zebrafish embryos using focal light activation of a photoactivatable Rac1. We outline techniques for photostimulation, time-lapse imaging, and immunohistochemistry. These approaches enable engineering of long-range axonal circuitry or repair of defective circuits in living zebrafish, despite a milieu of competing endogenous signals and repulsive barriers. For complete details on the use and execution of this protocol, please refer to Harris et al. (2020).
Johnson MS, Gopalakrishnan S, Goyal J, Dillingham ME, Bakerlee CW, Humphrey PT, Jagdish T, Jerison ER, Kosheleva K, Lawrence KR.
Phenotypic and molecular evolution across 10,000 generations in laboratory budding yeast populations. Elife. 2021;10 :e63910.
McCarthy GM, Blasio A, Donovan OG, Schaller LB, Bock-Hughes A, Magraner JM, Suh JH, Tattersfield CF, Stillman IE, Shah SS.
Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease. Disease Models & Mechanisms. 2021;14 (8) :dmm048952.
Seo BR, Payne CJ, McNamara SL, Freedman BR, Kwee BJ, Nam S, de Lázaro I, Darnell M, Alvarez JT, Dellacherie MO.
Skeletal muscle regeneration with robotic actuation–mediated clearance of neutrophils. Science translational medicine. 2021;13 (614) :eabe8868.
Richardson DS, Guan W, Matsumoto K, Pan C, Chung K, Erturk A, Ueda HR, Lichtman JW.
Tissue Clearing. Nat Rev Methods Primers. 2021;1 (1).
Publisher's VersionAbstractTissue clearing of gross anatomical samples was first described over a century ago and has only recently found widespread use in the field of microscopy. This renaissance has been driven by the application of modern knowledge of optical physics and chemical engineering to the development of robust and reproducible clearing techniques, the arrival of new microscopes that can image large samples at cellular resolution and computing infrastructure able to store and analyze large data volumes. Many biological relationships between structure and function require investigation in three dimensions and tissue clearing therefore has the potential to enable broad discoveries in the biological sciences. Unfortunately, the current literature is complex and could confuse researchers looking to begin a clearing project. The goal of this Primer is to outline a modular approach to tissue clearing that allows a novice researcher to develop a customized clearing pipeline tailored to their tissue of interest. Further, the Primer outlines the required imaging and computational infrastructure needed to perform tissue clearing at scale, gives an overview of current applications, discusses limitations and provides an outlook on future advances in the field.
Mills EL, Harmon C, Jedrychowski MP, Xiao H, Garrity R, Tran NV, Bradshaw GA, Fu A, Szpyt J, Reddy A.
UCP1 governs liver extracellular succinate and inflammatory pathogenesis. Nature metabolism. 2021;3 (5) :604-617.
Nagarkar AA, Root SE, Fink MJ, Ten AS, Cafferty BJ, Richardson DS, Mrksich M, Whitesides GM.
Storing and reading information in mixtures of fluorescent molecules. ACS central science. 2021;7 (10) :1728-1735.