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Abstract Biomaterial wound dressings, such as hydrogels, interact with host cells to regulate tissue repair. This study investigates how crosslinking of gelatin-based hydrogels influences immune and stromal cell behavior and wound healing in female mice. We observe that softer, lightly crosslinked hydrogels promote greater cellular infiltration and result in smaller scars compared to stiffer, heavily crosslinked hydrogels. Using single-cell RNA sequencing, we further show that heavily crosslinked hydrogels increase inflammation and lead to the formation of a distinct macrophage subpopulation exhibiting signs of oxidative activity and cell fusion. Conversely, lightly crosslinked hydrogels are more readily taken up by macrophages and integrated within the tissue. The physical properties differentially affect macrophage and fibroblast interactions, with heavily crosslinked hydrogels promoting pro-fibrotic fibroblast activity that drives macrophage fusion through RANKL signaling. These findings suggest that tuning the physical properties of hydrogels can guide cellular responses and improve healing, offering insights for designing better biomaterials for wound treatment. 

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue’s stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without “packing foam–like” extracellular matrix. 

Single-cell analysis of human basal cell carcinoma shows a WNT5A reactive stroma that promotes tumor HSP70 to maintain growth. 

Abstract We use medium-resolution Keck/Echellette Spectrograph and Imager spectroscopy of bright quasars to study cool gas traced by Caiiλλ3934, 3969 and Naiλλ5891, 5897 absorption in the interstellar/circumgalactic media of 21 foreground star-forming galaxies at redshifts 0.03 <z< 0.20 with stellar masses 7.4 ≤ logM_*/M_⊙≤ 10.6. The quasar–galaxy pairs were drawn from a unique sample of Sloan Digital Sky Survey quasar spectra with intervening nebular emission, and thus have exceptionally close impact parameters (R_⊥< 13 kpc). The strength of this line emission implies that the galaxies’ star formation rates (SFRs) span a broad range, with several lying well above the star-forming sequence. We use Voigt profile modeling to derive column densities and component velocities for each absorber, finding that column densitiesN(Caii) > 10^12.5cm⁻²(N(Nai) > 10^12.0cm⁻²) occur with an incidencef_C(Caii) = 0.63^+0.10_−0.11(f_C(Nai) = 0.57^+0.10_−0.11). We find no evidence for a dependence off_Cor the rest-frame equivalent widthsW_r(CaiiK) orW_r(Nai5891) onR_⊥orM_*. Instead,W_r(CaiiK) is correlated with local SFR at >3σsignificance, suggesting that Caiitraces star formation-driven outflows. While most of the absorbers have velocities within ±50 km s⁻¹of the host redshift, their velocity widths (characterized by Δv₉₀) are universally 30–177 km s⁻¹larger than that implied by tilted-ring modeling of the velocities of interstellar material. These kinematics must trace galactic fountain flows and demonstrate that they persist atR_⊥> 5 kpc. Finally, we assess the relationship between dust reddening andW_r(CaiiK) (W_r(Nai5891)), finding that 33% (24%) of the absorbers are inconsistent with the best-fit Milky WayE(B−V)-W_rrelations at >3σsignificance. 

Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in muscle disease remains unclear. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six clusters and unexpectedly found that none corresponded to traditional definitions of M1 or M2 macrophages. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 (gal-3) and osteopontin (Spp1). Spatial transcriptomics, computational inferences of intercellular communication, and in vitro assays indicated that macrophage-derived Spp1 regulates stromal progenitor differentiation. Gal-3⁺macrophages were chronically activated in dystrophic muscle, and adoptive transfer assays showed that the gal-3⁺phenotype was the dominant molecular program induced within the dystrophic milieu. Gal-3⁺macrophages were also elevated in multiple human myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining their transcriptional programs and revealSpp1as a major regulator of macrophage and stromal progenitor interactions. 

Infections are a major complication of obesity, but the mechanisms responsible for impaired defense against microbes are not well understood. Here, we found that adipocyte progenitors were lost from the dermis during diet-induced obesity (DIO) in humans and mice. The loss of adipogenic fibroblasts from mice resulted in less antimicrobial peptide production and greatly increased susceptibility to Staphylococcus aureus infection. The decrease in adipocyte progenitors in DIO mice was explained by expression of transforming growth factor–β (TGFβ) by mature adipocytes that then inhibited adipocyte progenitors and the production of cathelicidin in vitro. Administration of a TGFβ receptor inhibitor or a peroxisome proliferator–activated receptor–γ agonist reversed this inhibition in both cultured adipocyte progenitors and in mice and subsequently restored the capacity of obese mice to defend against S. aureus skin infection. Together, these results explain how obesity promotes dysfunction of the antimicrobial function of reactive dermal adipogenesis and identifies potential therapeutic targets to manage skin infection associated with obesity.