Source Selection for Cluster Weak Lensing Measurements in the Hyper Suprime-Cam Survey

We present optimized source galaxy selection schemes for measuring cluster weak lensing (WL) mass profiles unaffected by cluster member dilution from the Subaru Hyper Suprime-Cam Strategic Survey Program (HSC-SSP). The ongoing HSC-SSP survey will uncover thousands of galaxy clusters to $z\lesssim1.5$. In deriving cluster masses via WL, a critical source of systematics is contamination and dilution of the lensing signal by cluster {members, and by foreground galaxies whose photometric redshifts are biased}. Using the first-year CAMIRA catalog of $\sim$900 clusters with richness larger than 20 found in $\sim$140 deg$^2$ of HSC-SSP data, we devise and compare several source selection methods, including selection in color-color space (CC-cut), and selection of robust photometric redshifts by applying constraints on their cumulative probability distribution function (PDF; P-cut). We examine the dependence of the contamination on the chosen limits adopted for each method. Using the proper limits, these methods give mass profiles with minimal dilution in agreement with one another. We find that not adopting either the CC-cut or P-cut methods results in an underestimation of the total cluster mass ($13\pm4\%$) and the concentration of the profile ($24\pm11\%$). The level of cluster contamination can reach as high as $\sim10\%$ at $R\approx 0.24$ Mpc/$h$ for low-z clusters without cuts, while employing either the P-cut or CC-cut results in cluster contamination consistent with zero to within the 0.5% uncertainties. Our robust methods yield a $\sim60\sigma$ detection of the stacked CAMIRA surface mass density profile, with a mean mass of $M_\mathrm{200c} = (1.67\pm0.05({\rm {stat}}))\times 10^{14}\,M_\odot/h$.Comment: 19 pages, 4 tables, 12 figures, accepted to PASJ special issu

First Data Release of the Hyper Suprime-Cam Subaru Strategic Program

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered imaging survey aimed at addressing some of the most outstanding questions in astronomy today, including the nature of dark matter and dark energy. The survey has been awarded 300 nights of observing time at the Subaru Telescope and it started in March 2014. This paper presents the first public data release of HSC-SSP. This release includes data taken in the first 1.7 years of observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and ~27.0 mag, respectively (5sigma for point sources). All the layers are observed in five broad bands (grizy), and the Deep and UltraDeep layers are observed in narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF photometry (rms) both internally and externally (against Pan-STARRS1), and ~10 mas and 40 mas internal and external astrometric accuracy, respectively. Both the calibrated images and catalogs are made available to the community through dedicated user interfaces and database servers. In addition to the pipeline products, we also provide value-added products such as photometric redshifts and a collection of public spectroscopic redshifts. Detailed descriptions of all the data can be found online. The data release website is https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for publication in PAS

Hepatic progenitor cells of biliary origin with liver repopulation capacity

Hepatocytes and cholangiocytes self-renew following liver injury. Following severe injury hepatocytes are increasingly senescent, but whether hepatic progenitor cells (HPCs) then contribute to liver regeneration is unclear. Here, we describe a mouse model where the E3 ubiquitin ligase Mdm2 is inducibly deleted in more than 98% of hepatocytes, causing apoptosis, necrosis and senescence with nearly all hepatocytes expressing p21. This results in florid HPC activation, which is necessary for survival, followed by complete, functional liver reconstitution. HPCs isolated from genetically normal mice, using cell surface markers, were highly expandable and phenotypically stable in vitro. These HPCs were transplanted into adult mouse livers where hepatocyte Mdm2 was repeatedly deleted, creating a non-competitive repopulation assay. Transplanted HPCs contributed significantly to restoration of liver parenchyma, regenerating hepatocytes and biliary epithelia, highlighting their in vivo lineage potency. HPCs are therefore a potential future alternative to hepatocyte or liver transplantation for liver disease

The Hyper Suprime-Cam SSP survey: Overview and survey design

Hyper Suprime-Cam (HSC) is a wide-field imaging camera on the prime focus of the 8.2-m Subaru telescope on the summit of Mauna Kea in Hawaii. A team of scientists from Japan, Taiwan, and Princeton University is using HSC to carry out a 300-night multi-band imaging survey of the high-latitude sky. The survey includes three layers: the Wide layer will cover 1400 deg2 in five broad bands (grizy), with a 5 σ point-source depth of r ≈ 26. The Deep layer covers a total of 26 deg2 in four fields, going roughly a magnitude fainter, while the UltraDeep layer goes almost a magnitude fainter still in two pointings of HSC (a total of 3.5 deg2). Here we describe the instrument, the science goals of the survey, and the survey strategy and data processing. This paper serves as an introduction to a special issue of the Publications of the Astronomical Society of Japan, which includes a large number of technical and scientific papers describing results from the early phases of this survey

Expression of Jak2V617F causes a polycythemia vera–like disease with associated myelofibrosis in a murine bone marrow transplant model

An acquired somatic mutation, Jak2V617F, was recently discovered in most patients with polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), and essential thrombocythemia (ET). To investigate the role of this mutation in vivo, we transplanted bone marrow (BM) transduced with a retrovirus expressing either Jak2 wild-type (wt) or Jak2V617F into lethally irradiated syngeneic recipient mice. Expression of Jak2V617F, but not Jak2wt, resulted in clinicopathologic features that closely resembled PV in humans. These included striking elevation in hemoglobin level/hematocrit, leukocytosis, megakaryocyte hyperplasia, extramedullary hematopoiesis resulting in splenomegaly, and reticulin fibrosis in the bone marrow. Histopathologic and flow cytometric analyses showed an increase in maturing myeloid lineage progenitors, although megakaryocytes showed decreased polyploidization and staining for acetylcholinesterase. In vitro analysis of primary cells showed constitutive activation of Stat5 and cytokine-independent growth of erythroid colony-forming unit (CFU-E) and erythropoietin hypersensitivity, and Southern blot analysis for retroviral integration indicated that the disease was oligoclonal. Furthermore, we observed strain-specific differences in phenotype, with Balb/c mice demonstrating markedly elevated leukocyte counts, splenomegaly, and reticulin fibrosis compared with C57Bl/6 mice. We conclude that Jak2V617F expression in bone marrow progenitors results in a PV-like syndrome with myelofibrosis and that there are strain-specific modifiers that may in part explain phenotypic pleiotropy of Jak2V617F-associated myeloproliferative disease in humans

Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD

Acquired mutations in the FLT3 receptor tyrosine kinase are common in acute myeloid leukemia and result in constitutive activation. The most frequent mechanism of activation is disruption of the juxtamembrane autoregulatory domain by internal tandem duplications (ITDs). FLT3-ITDs confer factor-independent growth to hematopoietic cells and induce a myeloproliferative syndrome in murine bone marrow transplant models. We and others have observed that FLT3-ITD activates STAT5 and its downstream effectors, whereas ligand-stimulated wild-type FLT3 (FLT3WT) does not. In vitro mapping of tyrosine phosphorylation sites in FLT3-ITD identified 2 candidate STAT5 docking sites within the juxtamembrane domain that are disrupted by the ITD. Tyrosine to phenylalanine substitution of residues 589 and 591 in the context of the FLT3-ITD did not affect tyrosine kinase activity, but abrogated STAT5 activation. Furthermore, FLT3-ITD–Y589/591F was incapable of inducing a myeloproliferative phenotype when transduced into primary murine bone marrow cells, whereas FLT3-ITD induced myeloproliferative disease with a median latency of 50 days. Thus, the conformational change in the FLT3 juxtamembrane domain induced by the ITD activates the kinase through dysregulation of autoinhibition and results in qualitative differences in signal transduction through STAT5 that are essential for the transforming potential of FLT3-ITD in vivo

MSI2 Is Required for Maintaining the Activated Myelodysplastic Syndrome Stem Cell

Abstract + The first four authors contributed equally to this project. Myelodysplastic syndromes (MDS) are a group of blood cell disorders, characterized by ineffective hematopoiesis and severe cytopenias, which often transform to acute leukemia. MDS is also considered to be a clonal stem cell disease driven by alterations that are both genetic and epigenetic. However, it remains unclear how stem cell function is dysregulated and what factors drive these alterations in MDS HSCs. MSI2 is an important RNA-binding protein in normal HSC maintenance and can promote aggressive myeloid leukemia. Our preliminary data indicate that MSI2 expression is increased in high-risk MDS compared to low-risk MDS and correlates with poor survival. In order to model the role of MSI2 in MDS, we utilized the NUP98-HOXD13 transgenic (NHD13) model, which recapitulates many salient features of MDS including, leukopenia, severe anemia, erythroid dysplasia and leukemic transformation. Despite the lethal MDS or AML disease found in primary NHD13 animals, bone marrow cells transplanted into congenic mice generate a non-lethal MDS that rarely transform. Depletion of Msi2 utilizing a conditional knockout (NHD13-Msi2f/f -MX1-Cre) reversed the MDS phenotype and after one month the diseased HSPCs were eliminated. Conversely, we found that tetracycline inducible MSI2 overexpression in the context of the NHD13 transgene (NHD13/MSI2 mice) resulted in a worse MDS disease and a fully penetrant and lethal transformation to an AML, which was further accelerated during serial transplantation. AML arising in NHD13/MSI2 mice remained dependent on sustained MSI2 overexpression as mice removed from doxycycline demonstrated improved survival. Most interestingly, MSI2 overexpression expanded and maintained a more activated (G1) MDS hematopoietic stem and progenitor compartment (HSPC) in NHD13 cells. Gene expression profiling of the LSKs (Lineagelo, c-Kit+, Sca1+) before disease progression identified 891 significant genes, of which 137 genes were up-regulated (log2 fold change > 0) and 754 genes were down-regulated (log2 fold change <= 0). Furthermore, Gene Set Enrichment Analysis (GSEA) demonstrated a more progenitor like gene expression signature, enrichment in an NRAS activated signature, and a reduced quiescent phenotype. Unsupervised hierarchical clustering of the NHD13/MSI2 LSK gene signature in MDS patients resulted in four distinct clusters. Clusters segregated MSI2 high expressing MDS patients and this "MSI2 high cluster" predicted poor survival. In summary, our findings suggest that MSI2 plays a critical functional role in the maintenance of the hematopoietic stem and progenitor compartment in MDS and highlights it as a novel therapeutic target in this disease. Disclosures No relevant conflicts of interest to declare