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Currlin, S.

Publications and source records attributed to Currlin, S..

3 recordsLinked to original sources

3D imaging of human pancreas suggests islet size and endocrine composition influence their loss in type 1 diabetes

A high-definition description of pancreatic islets would prove beneficial for understanding the pathophysiology of type 1 diabetes (T1D), yet significant knowledge voids exist in terms of their size, endocrine cell composition, and number in both health and disease. Here, 3-dimensional (3D) analyses of pancreata from control persons without diabetes (ND) revealed heretofore underappreciated frequencies (approximately 50%) of insulin-positive (INS+) glucagon-negative (GCG-) islets. Non-diabetic individuals positive for a single Glutamic acid decarboxylase autoantibody (GADA+) yet at increased risk for disease consistently demonstrated endocrine features, including islet volume and cell composition, closely resembling the age-matched ND controls. In contrast, pancreata from individuals with short-duration T1D demonstrated significantly reduced islet density and a dramatic loss of INS+GCG- islets with preservation of large INS+GCG+ islets. The size and cellular composition of pancreatic islets may, therefore, represent influential factors that impact {beta}-cell loss during T1D disease progression. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/654045v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1d2fdeaorg.highwire.dtl.DTLVardef@11c43edorg.highwire.dtl.DTLVardef@af8a82org.highwire.dtl.DTLVardef@ae8c58_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LI3D imaging of non-diabetic (ND) pancreas suggests up to 50% of INS+ islets lack GCG C_LIO_LIINS+GCG- islets are typically small-sized in ND and preferentially lost in T1D C_LIO_LIIn T1D pancreas, INS+ beta cells are preserved in large INS+GCG+ islets C_LIO_LIIslets from GADA+ individuals appear similar to ND for size and {beta}-to- cell ratios C_LI

pathology↗

3D-mapping of human lymph node and spleen reveals integrated neuronal, vascular, and ductal cell networks

The spleen and lymph node represent important hubs for both innate and adaptive immunity1,2. Herein, we map immune, endothelial, and neuronal cell networks within these tissues from "normal"/non-diseased organ donors, collected through the NIH Human BioMolecular Atlas Program (HuBMAP)3, using highly multiplexed CODEX (CO-Detection by indEXing) imaging and 3D light sheet microscopy of cleared tissues. Building on prior reports4-6, we observed the lymph node subcapsular sinus expressing podoplanin, smooth muscle actin, and LYVE1. In the spleen, LYVE1 was expressed by littoral cells lining venous sinusoids, whereas podoplanin was restricted to arteries and trabeculae. 3D visualization of perivascular innervation revealed a subset of axonal processes expressing choline acetyl transferase in both tissues, in contrast with prior literature on human spleen7. We further report our novel observations regarding the distinct localization of GAP43 and {beta}3-tubulin within the vascular anatomy of both lymph node and spleen, with Coronin-1A+ cells forming a dense cluster around {beta}3-tubulin positive GAP43 low/negative segments of large vessels in spleen. These data provide an unprecedented 2D and 3D visualization of cellular networks within secondary lymphoid tissues, laying the groundwork for future disease-specific and system-wide studies of neural regulation of immunity in human lymphatics.

immunology↗

Differential Expression of Immune Related Genes in Taste Buds of Fed and Fasted Mice

To study the effects of feeding on taste receptor cell transcriptional regulation, we performed RNA-seq analysis of circumvallate taste buds isolated from mice before or after food consumption. Here we report and compare the taste bud transcriptomes obtained from food-deprived, satiated, and ad libitum fed control mice. Despite sample heterogeneity inherent to the whole taste bud transcriptome, bioinformatics analysis yielded 144 differentially expressed transcripts associated with immunity, cytoskeletal structure, and protein folding between these groups. We also profiled the transcriptome obtained from ad libitum fed control mice based on receptor related gene ontology terms, demonstrating a use of this dataset in the identification of novel TRC receptors. The data presented here suggest that transcriptional regulation of immune cytokine signaling occurs in TRCs shortly after meal consumption, though additional analysis is required to confirm this hypothesis.

bioinformatics↗