It is not known how long it takes from the initial neoplastic transformation of a cell to the detection of a tumor, which would be valuable for understanding tumor growth dynamics. Meningiomas show a ...broad histological, genetic and clinical spectrum, are usually benign and considered slowly growing. There is an intense debate regarding their age and growth pattern and when meningiomas should be resected. We have assessed the age and growth dynamics of 14 patients with meningiomas (WHO grade I: n=6 with meningothelial and n=6 with fibrous subtype, as well as n=2 atypical WHO grade II meningiomas) by combining retrospective birth-dating of cells by analyzing incorporation of nuclear-bomb-test-derived 14C, analysis of cell proliferation, cell density, MRI imaging and mathematical modeling. We provide an integrated model of the growth dynamics of benign meningiomas. The mean age of WHO grade I meningiomas was 22.1±6.5years, whereas atypical WHO grade II meningiomas originated 1.5±0.1years prior to surgery (p<0.01). We conclude that WHO grade I meningiomas are very slowly growing brain tumors, which are resected in average two decades after time of origination.
•The age of meningiomas has been difficult to study and is not understood, however age and growth dynamics may affect clinical decision making regarding surgery•We determined the age and dynamics of meningioma tumor cells using 14C retrospective birth dating strategy together with MR imaging and histological parameters•We demonstrate that the average time between initial tumorous cell transformation and detection with resection is 26.3years in fibrous and years in 17.8 meningothelial meningiomas
Meningiomas are usually benign, slowly growing and frequently occurring brain tumors that are detected incidentally upon imaging or because of causing symptoms. Many tumors remain stable, while others keep growing, why there is a debate whether or not meningiomas need surgical resection upon diagnosis. Specifically, if tumors grow in difficultly accessible brain areas, it would be clinically valuable to predict their age and growth dynamics. The 14C (radiocarbon) retrospective birth dating technique, an approach taking advantage of the above-ground atomic bomb tests during the Cold War, harbors the unique feature of dating the tumor age, thus providing insights into tumor origination and growth. Using this technique we here establish the age of meningiomas and provide an integrated model – using also MRI and histological parameters – to predict future growth of detected meningiomas, which may help in clinical decision making whether to resect the tumor.
Physiological liver cell replacement is central to maintaining the organ’s high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective radiocarbon ...(14C) birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing the liver to remain a young organ (average age <3 years). Hepatocyte renewal is highly dependent on the ploidy level. Diploid hepatocytes show more than 7-fold higher annual birth rates than polyploid hepatocytes. These observations support the view that physiological liver cell renewal in humans is mainly dependent on diploid hepatocytes, whereas polyploid cells are compromised in their ability to divide. Moreover, cellular transitions between diploid and polyploid hepatocytes are limited under homeostatic conditions. With these findings, we present an integrated model of homeostatic liver cell generation in humans that provides fundamental insights into liver cell turnover dynamics.
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•Retrospective 14C birth dating establishes the age of the human liver (<3 years)•Renewal rates of adult hepatocytes are independent of subject age•Diploid hepatocytes show more than 7-fold higher birth rates compared with polyploid•Contribution of higher ploidy levels to the diploid hepatocyte pool is limited
Based on radiocarbon birth dating, a comprehensive model of hepatocyte renewal in humans shows that the liver remains a young organ. Hepatocytes display a continuous and lifelong turnover, which is highly dependent on their ploidy level.
Muscle regeneration relies on the regulation of muscle stem cells (MuSCs) through paracrine signaling interactions. We analyzed muscle regeneration in mice using single-cell RNA sequencing ...(scRNA-seq) and generated over 34,000 single-cell transcriptomes spanning four time-points. We identified 15 distinct cell types including heterogenous populations of muscle stem and progenitor cells. We resolved a hierarchical map of these myogenic cells by trajectory inference and observed stage-specific regulatory programs within this continuum. Through ligand-receptor interaction analysis, we identified over 100 candidate regeneration-associated paracrine communication pairs between MuSCs and non-myogenic cells. We show that myogenic stem/progenitor cells exhibit heterogeneous expression of multiple Syndecan proteins in cycling myogenic cells, suggesting that Syndecans may coordinate myogenic fate regulation. We performed ligand stimulation in vitro and confirmed that three paracrine factors (FGF2, TGFβ1, and RSPO3) regulate myogenic cell proliferation in a Syndecan-dependent manner. Our study provides a scRNA-seq reference resource to investigate cell communication interactions in muscle regeneration.
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•Single-cell RNA-sequencing identifies cell populations involved in muscle regeneration•Muscle stem/progenitor cells form a hierarchy with stage-specific regulatory programs•Bioinformatic analysis identified paracrine factors influencing muscle stem cells•Syndecan-1/2/4 coordinate paracrine ligand-specific muscle progenitor proliferation
De Micheli et al. present an annotated, time-resolved single-cell transcriptomic atlas of muscle regeneration in adult mice. They observe a hierarchy of muscle stem and progenitor cells that exhibit stage-specific expression programs and show that Syndecan proteins regulate muscle progenitor cell fates by interaction with newly discovered paracrine communication factors.
Postural deformities often manifest themselves in a sagittal imbalance and an asymmetric morphology of the torso. As a novel topographic method, torsobarography assesses the morphology of the back by ...analysing pressure distribution along the torso in a lying position. At torsobarography's core is a capacitive pressure sensor array. To evaluate its feasibility as a diagnostic tool, the reproducibility of the system and extracted anatomical associated parameters were evaluated on 40 subjects. Landmarks and reference distances were identified within the pressure images. The examined parameters describe the shape of the spine, various structures of the trunk symmetry, such as the scapulae, and the pelvic posture. The results showed that the localisation of the different structures performs with a good (ICC > 0.75) to excellent (ICC > 0.90) reliability. In particular, parameters for approximating the sagittal spine shape were reliably reproduced (ICC > 0.83). Lower reliability was observed for asymmetry parameters, which can be related to the low variability within the subject group. Nonetheless, the reliability levels of selected parameters are comparable to commercial systems. This study demonstrates the substantial potential of torsobarography at its current stage for reliable posture analysis and may pave the way as an early detection system for postural deformities.
In an attempt to more completely define the histopathologic features of the portal vein hyperperfusion or small-for-size syndrome (PHP/SFSS), we strictly identified 5 PHP/SFSS cases among 39 (5/39; ...13%) adult living donor liver transplants (ALDLT) completed between 11/01 and 09/03. Living donor segments consisting of 3 right lobes, 1 left lobe, and 1 left lateral segment, with a mean allograft-to-recipient weight ratio (GRWR) of 1.0 +/- 0.3 (range 0.6 to 1.4), were transplanted without complications, initially, into 6 relatively healthy 25 to 63-year-old recipients. However, all recipients developed otherwise unexplained jaundice, coagulopathy, and ascites within 5 days after transplantation. Examination of sequential posttransplant biopsies and 3 failed allografts with clinicopathologic correlation was used in an attempt to reconstruct the sequence of events. Early findings included: (1) portal hyperperfusion resulting in portal vein and periportal sinusoidal endothelial denudation and focal hemorrhage into the portal tract connective tissue, which dissected into the periportal hepatic parenchyma when severe; and (2) poor hepatic arterial flow and vasospasm, which in severe cases, led to functional dearterialization, ischemic cholangitis, and parenchymal infarcts. Late sequelae in grafts surviving the initial events included small portal vein branch thrombosis with occasional luminal obliteration or recanalization, nodular regenerative hyperplasia, and biliary strictures. These findings suggest that portal hyperperfusion, venous pathology, and the arterial buffer response importantly contribute to early and late clinical and histopathologic manifestations of the small-for-size syndrome.
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