High-Throughput Assembly of Compositionally Controlled 3D Cell Communities for Developmental Engineering.

Cell patterning for 3D culture has increased our understanding of how cells interact among themselves and with their environment during tissue morphogenesis. Building cell communities from the bottom up with size and compositional control is invaluable for studies of morphological transitions. Here, we detail Photolithographic DNA-programmed Assembly of Cells (pDPAC).

Nephron progenitors rhythmically alternate between renewal and differentiation phases that synchronize with kidney branching morphogenesis.

The mammalian kidney achieves massive parallelization of function by exponentially duplicating nephron-forming niches during development. Each niche caps a tip of the ureteric bud epithelium (the future urinary collecting duct tree) as it undergoes branching morphogenesis, while nephron progenitors within niches balance self-renewal and differentiation to early nephron cells. Nephron formation rate approximately matches branching rate over a large fraction of mouse gestation, yet the nature of this apparent pace-maker is unknown.

Rho/ROCK activity tunes cell compartment segregation and differentiation in nephron-forming niches.

Controlling the time and place of nephron formation would improve nephron density and connectivity in next-generation kidney replacement tissues. Recent developments in kidney organoid technology have paved the way to achieving self-sustaining nephrogenic niches . The physical and geometric structure of the niche are key control parameters in tissue engineering approaches.

Independent control over cell patterning and adhesion on hydrogel substrates for tissue interface mechanobiology.

Tissue boundaries and interfaces are engines of morphogenesis . However, despite a wealth of micropatterning approaches available to control tissue size, shape, and mechanical environment , fine-scale spatial control of cell positioning within tissue constructs remains an engineering challenge. To address this, we augment DNA "velcro" technology for selective patterning of ssDNA-labeled cells on mechanically defined photoactive polyacrylamide hydrogels.

The developing murine kidney actively negotiates geometric packing conflicts to avoid defects.

The physiological functions of several organs rely on branched epithelial tubule networks bearing specialized structures for secretion, gas exchange, or filtration. Little is known about conflicts in development between building enough tubules for adequate function and geometric constraints imposed by organ size. We show that the mouse embryonic kidney epithelium negotiates a physical packing conflict between increasing tubule tip numbers through branching and limited organ surface area.

Guiding Cell Network Assembly using Shape-Morphing Hydrogels.

Forces and relative movement between cells and extracellular matrix (ECM) are crucial to the self-organization of tissues during development. However, the spatial range over which these dynamics can be controlled in engineering approaches is limited, impeding progress toward the construction of large, structurally mature tissues. Herein, shape-morphing materials called "kinomorphs" that rationally control the shape and size of multicellular networks are described.

Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females.

Sugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-coenzyme A (CoA) for both lipid synthesis and acetylation reactions. Here, we investigate the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes and unexpectedly uncover a sexually dimorphic function in maintaining systemic metabolic homeostasis.

Impact of a High-fat Diet on Tissue Acyl-CoA and Histone Acetylation Levels.

Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood but could alter gene expression and influence metabolic health. ATP citrate-lyase produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types.

ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch.

Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA) plays central roles in energy production, lipid metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY), cells remain viable and proliferate, although at an impaired rate.