The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis

Abstract

Pancreatic cancer is characterized by abundant desmoplasia, a dense stroma composed of extra-cellular and cellular components, with cancer associated fibroblasts (CAFs) being the major cellular component. However, the tissue(s) of origin for CAFs remains controversial. Here we determine the tissue origin of pancreatic CAFs through comprehensive lineage tracing studies in mice. We find that the splanchnic mesenchyme, the fetal cell layer surrounding the endoderm from which the pancreatic epithelium originates, gives rise to the majority of resident fibroblasts in the normal pancreas. In a genetic mouse model of pancreatic cancer, resident fibroblasts expand and constitute the bulk of CAFs. Single cell RNA profiling identifies gene expression signatures that are shared among the fetal splanchnic mesenchyme, adult fibroblasts and CAFs, suggesting a persistent transcriptional program underlies splanchnic lineage differentiation. Together, this study defines the phylogeny of the mesenchymal component of the pancreas and provides insights into pancreatic morphogenesis and tumorigenesis.

Rose-like NiCo2O4 with Atomic-Scale Controllable Oxygen Vacancies for Modulating Sulfur Redox Kinetics in Lithium–Sulfur Batteries

“…The relative intensities of the (311) and (400) crystal planes change, and the lattice of NiCo 2 O 4 undergoes orientation changes during the reduction process. 52,53 The Raman test results are shown in Figure S6, and all the materials show characteristic peaks at 186, 321, 462, and 656 cm −1 , which correspond to the four Raman vibrational modes of F 2g , E g , F 2g , and A 1g of NiCo 2 O 4 , respectively, 54 and A 1g at 656 cm −1 was significantly negatively shifted, which suggests that the formation of O V attenuates the in-plane vibration of the bonding between the metal and the oxygen, 55,56 and the shifting of the characteristic peaks of Raman suggests the occurrence of more O V in the materials. 57 Aside from the typical characterization techniques mentioned earlier, electron paramagnetic resonance (EPR) allows for trace analysis of the unpaired electronic states of NiCo 2g; the samples all exhibit significant EPR signals, and after calculation g = 2.003, which is the characteristic value of O V .…”

4D printed shape-shifting biomaterials for tissue engineering and regenerative medicine applications

“…However, DIW requires post-processing steps for solidification that can be time-consuming. Materials that have been used in DIW applications include nanocomposite polymeric solutions [46], hydrogels [47], resins embedded in a supporting matrix [48], metal/bioceramic-based inks [49] and ceramic slurries [50]. The inks are placed in a reservoir or cartridge and extruded as continuous filaments using a pneumatic pump or a mechanical piston or screw (figure 2(c)).…”

Ce Single-Atom Incorporation Enhances the Oxygen Evolution Reaction of Co3O4 in Acid

“…In addition, the synergistic effect between the active species and the Ti elements gave them excellent OER activity. Moreover, Jin and co-workers 14 reported a redoped rutile RuO 2 electrocatalyst in which the Re dopant undergoes dynamic electron accepting−donating, resulting in excellent OER performance in acidic media.…”