Biology subjects

King, C. S.

Publications and source records attributed to King, C. S..

2 recordsLinked to original sources

bioRxiv2024

Loss of Bicra/Gltscr1 leads to a defect in fetal liver macrophages responsible for erythrocyte maturation in mice.

Key pointsBicra/Gltscr1 homozygous knockout mice are perinatal lethal with aberrant liver resident macrophage gene expression and function. Dysfunctional macrophages result in accumulation of immature nucleated red blood cells in peripheral blood and liver of the knockout mice. GLTSCR1, a protein encoded by the Bicra gene, is a defining subunit of the SWI/SNF (also called mammalian BAF) chromatin remodeling subcomplex called GBAF/ncBAF. To determine the role of GLTSCR1 during mouse development, we generated a Bicra germline knockout mouse using CRISPR/Cas9. Mice with homozygous loss of Bicra were born at Mendelian ratios but were small, pale and died within 24 hours after birth. Histology indicated blood-related defects including defective erythroblastic islands and irregularly sized red blood cells. Gene expression profiling of fetal livers pinpointed a defect in liver resident macrophages involved in the last stage of erythrocyte maturation, resulting in accumulation of nucleated erythrocytes in Bicra-/- pups. Together, these results demonstrate that Bicra is critical for fetal liver macrophage function during development. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/618940v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@150ac36org.highwire.dtl.DTLVardef@15a4758org.highwire.dtl.DTLVardef@2176aorg.highwire.dtl.DTLVardef@14f5d49_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOVisual AbstractC_FLOATNO C_FIG

developmental biology↗

bioRxiv2023

Pulmonary Matrix Derived Hydrogels from Patients with Idiopathic Pulmonary Fibrosis Induce a Proinflammatory State in Lung Fibroblasts In Vitro

Idiopathic pulmonary fibrosis (IPF), one of the most common forms of interstitial lung disease, is a poorly understood, chronic, and often fatal fibroproliferative condition with only two FDA-approved medications. Understanding the pathobiology of the fibroblast in IPF is critical to evaluating and discovering novel therapeutics. Unfortunately, our ability to interrogate this biology in vitro is greatly limited by the well-documented effects of tissue culture plastic on the fibroblast phenotype. Using a decellularized lung matrix derived from IPF patients, we generate three-dimensional (3D) hydrogels as in vitro models of lung physiology and characterize the phenotype of fibroblasts seeded into the hydrogels. When cultured in our hydrogels, IPF fibroblasts display differential contractility compared to their normal counterparts, lose the classical myofibroblast marker -smooth muscle actin, and increase expression of proinflammatory cytokines compared to fibroblasts seeded two-dimensionally (2D) on tissue culture dishes. We validate this proinflammatory state in fibroblast conditioned media studies with monocytes and monocyte-derived macrophages. These findings add to a growing understanding of the lung microenvironment effect on fibroblast phenotypes, shed light on the potential role of fibroblasts as immune signaling hubs during lung fibrosis, and suggest intervention in fibroblast-immune cell crosstalk as a possible novel therapeutic avenue.

molecular biology↗