BaCKgRoUND aND aIMS: Studies of the identity and pathophysiology of fibrogenic HSCs have been hampered by a lack of genetic tools that permit specific and inducible fate-mapping of these cells in vivo. Here, by single-cell RNA sequencing of nonparenchymal cells from mouse liver, we identified transcription factor 21 (Tcf21) as a unique marker that restricted its expression to quiescent HSCs. appRoaCH aND ReSUltS: Tracing Tcf21 + cells by Tcf21-CreER (Cre-Estrogen Receptor fusion protein under the control of Tcf21 gene promoter) targeted ~10% of all HSCs, most of which were located at periportal and pericentral zones. These HSCs were quiescent under steady state but became activated on injuries, generating 62%-67% of all myofibroblasts in fibrotic livers and ~85% of all cancer-associated fibroblasts (CAFs) in liver tumors. Conditional deletion of Transforming Growth Factor Beta Receptor 2 (Tgfbr2) by Tcf21-CreER blocked HSC activation, compromised liver fibrosis, and inhibited liver tumor progression. CoNClUSIoNS:In conclusion, Tcf21-CreER-targeted perivenous stellate cells are the main source of myofibroblasts and CAFs in chronically injured livers. TGFβ signaling links HSC activation to liver fibrosis and tumorigenesis.
It is challenging to search for high T c superconductivity (SC) in transition metal elements wherein d electrons are usually not favored by conventional BCS theory. Here we report experimental discovery of surprising SC up to 310 GPa with T c above 20 K in wide pressure range from 108 GPa to 240 GPa in titanium. The maximum T c onset above 26.2 K and zero resistance T c zero of 21 K are record high values hitherto achieved among element superconductors. The H c2 (0) is estimated to be ∼32 Tesla with coherence length 32 Å. The results show strong s-d transfer and d band dominance, indicating correlation driven contributions to high T c SC in dense titanium. This finding is in sharp contrast to the theoretical predications based on pristine electron-phonon coupling scenario. The study opens a fresh promising avenue for rational design and discovery of high T c superconductors among simple materials via pressure tuned unconventional mechanism.Titanium (Ti) metal has long attracted tremendous scientific interests because of its combined properties of light weight, high strength and corrosion resistance. As an advanced metallic structural material, Ti and its alloys find wide use in the fields of aerospace, biomedicine and at extreme conditions 1-3 . High pressure can modify crystal structures which, in turn, may lead to new functionalities. At ambient pressure and room temperature, Ti crystalizes in a hexagonal close-packed (hcp) structure (Ti-α phase) 4 . Under applied pressure, Ti undergoes structural transitions in the sequence of Ti-α, Ti-ω, Ti-γ, Ti-δ, and Ti-β phases, where Ti-ω phase is a hexagonal structure, Ti-γ and Ti-δ phases are orthorhombic and Ti-β phase is body-centered cubic [5][6][7][8][9] . The α-to-ω transition occurs around 8 GPa 5,6 , and the Ti-ω phase is stable up to about 100 GPa, then transforms into Ti-γ phase 6,10 , which further transforms into Tiδ phase at ~140 GPa 6 , before cubic Ti-β phase stabilizes at 243 GPa 9 . Superconductivity (SC) in high-pressure phases of Ti metal was previously reported to have a measured maximal critical temperature (T c ) of 3.5 K at 56 GPa 11 ; early theoretical calculations based on the electron-phonon coupling mechanism predicate that the T c for Ti metal is capped at about 5 K for all the known high-pressure phases 12 . Generally, compression of crystal lattice has markedly different effects on the 4s and 3d bands, prompting notable s-d electron transfer. The narrower d bands possess stronger correlation characters, while the s-d transfer tends to enhance electronic density of state (DOS) near the Fermi level in favor of SC [13][14][15][16][17] . Here, we report a surprising experimental observation of dramatic pressure enhanced SC in Ti over a wide
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