COVER The drawing evokes the powerful and momentous potential of cell engineering. The ability to alter cellular regulatory circuitry enables researchers to design modified cells to advance basic science and improve therapies. Investigators can now modify various cell types or groups of cells to operate as smart agents that facilitate experimentation or execute diagnostic or therapeutic functions. See the special section beginning on page 846.

Illustration: Jason Lyon

ONLINE COVER Simulation of a hybrid silicon nanoantenna array on a magnetic field. Digital camera sensors use color filters to selectively capture certain color spectrums. Traditional color filters are separate from the photosensitive silicon that makes up the sensor, causing optical cross-talk which limits the minimum possible pixel size. Ho et al. designed a hybrid silicon-aluminum nanoantenna that would allow the filter and sensor to be close enough together to achieve sub-micron pixel dimensions. This design could replace the traditional dye-based filters in ultra-high pixel density camera sensors.

ONLINE COVER Rejuvenation Potential of T_RM Subsets. This month’s cover depicts a “fountain of youth” from which new tissue resident memory T cells (T_RM) are emerging after a secondary infectious challenge. Newly formed CD103^– T_RM (blue) and CD103⁺ T_RM (red) are derived from proliferating, CD103^– precursor cells and join the pool of preexisting CD103⁺ T_RM (gray) that lack this restorative capacity. This model for T_RM replenishment is supported by new fate-mapping mouse models described in separate papers by von Hoesslin and Kuhlmann et al. and Fung et al. that are discussed in a Focus by Jensen and Farber.

ONLINE COVER Bionics replicate biomechanics. Lower-limb prostheses are often heavy, consume a lot of energy, and do not replicate the natural gait. Tran et al. have developed a powered prosthesis for above-knee amputees that possesses knee, ankle, and toe joints to replicate the biomechanics of the leg. The device is lightweight and capable of regenerating energy during walking to extend its battery life. The researchers validated their design with preclinical studies on above-knee amputees showing the ability to ambulate on level ground and on stairs. This month’s cover is a photograph of the prosthesis device: Utah Bionic Leg.

ONLINE COVER This week, Ye et al. use a human skin model combined with proteomic and phosphoproteomic analyses to reveal the requirements for distinct TGF-β signaling pathways in epidermal development and homeostasis. The image shows a 3D skin model in which the epithelial cells lack the receptor TGF-βRII, causing thickening of the epidermal layer, invasive growth of epidermal cells (green) into the basal compartment, and disruption of the basement membrane (red).

ONLINE COVER Restoring RBM20. This image shows cardiac tissue from mice carrying an R636Q mutation in the gene encoding RNA binding motif protein 20 (RBM20). In this image, precise in vivo adenine base editing (ABE) has restored the localization of RBM20 (green) to the nucleus (blue) and markedly reduced ribonucleoprotein granules outside the nucleus (cardiac troponin T is shown in red). Nishiyama et al. used ABE and prime editing to precisely correct mutations in RBM20, which are common causes of familial dilated cardiomyopathy, in pluripotent stem cells in vitro. In R636Q/R636Q mice, ABE resulted in improved RBM20 localization, cardiac function, and lifespan, suggesting that these precise editing approaches may be able to treat familial dilated cardiomyopathies.