In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2.


:Identification of genes involved in in vitro differentiation induction of embryonic stem cells (ESCs) into hematopoietic stem cells (HSCs) has been challenged during last decade. To date, a homeobox transcription factor Hoxb4 has been only demonstrated to possess such an effect in mice. Here, we show that HSC-like cells were efficiently induced from mouse ESCs by enforced expression of Lhx2, a LIM-homeobox transcription factor. Transduction of Lhx2 into ESC-derived mesodermal cells resulted in robust differentiation of c-Kit(+)/Sca-1(+)/Lineage(-) (KSL) cells in vitro. The KSL cell induction frequency was superior to the case of Hoxb4. Furthermore, transplantation of Lhx2-transduced hematopoietic cells into lethally irradiated mice resulted in multilineage repopulation of hematopoietic cells over 4 months. Transduction of Lhx2 into induced pluripotent stem cells (iPSCs) was also effective in generating KSL cells in vitro, as well as HSC-like activities in vivo. These results demonstrate that ectopic expression of Lhx2 confers an in vivo engrafting capacity to ESC/iPSC-derived hematopoietic cells and in vivo behavior of iPSC-derived hematopoietic cells is almost identical to that of ESC-derived cells.






Kitajima K,Minehata K,Sakimura K,Nakano T,Hara T




Has Abstract


2011-04-07 00:00:00
















  • Human neutrophils release the Leu-8 lymph node homing receptor during cell activation.

    abstract::The Leu-8 molecule, the human homologue of the murine MEL-14 peripheral lymph node homing receptor, is expressed on neutrophils in both species and may be important in localization of cells to sites of inflammation. Most circulating human neutrophils express the Leu-8 molecule, and activation of neutrophils with phorb...


    pub_type: 杂志文章


    authors: Berg M,James SP

    更新日期:1990-12-01 00:00:00

  • Factors affecting antibody levels after allogeneic hematopoietic cell transplantation.

    abstract::To obtain insight into the mechanism(s) of posttransplantation humoral immunodeficiency, we evaluated factors affecting serum antibody levels against polio, tetanus, Haemophilus influenzae, and Streptococcus pneumoniae in 87 patients. Patients with hematologic malignancies were randomized to receive marrow versus bloo...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Storek J,Viganego F,Dawson MA,Herremans MM,Boeckh M,Flowers ME,Storer B,Bensinger WI,Witherspoon RP,Maloney DG

    更新日期:2003-04-15 00:00:00

  • Use of prothrombin complex concentrates in the treatment of a hemophilic patient with an inhibitor of factor VIII.

    abstract::The course and treatment of a life-threatening hemorrhagic episode in a patient with hemophilia A whose plasma contained a high concentration of an inhibitor of factor VIII activity is presented. The inhibitor of factor VIII was localized to the most anodal fractions of immunoglobulin G on electrophoresis, and was thu...


    pub_type: 杂志文章


    authors: Sonoda T,Solomon A,Krauss S,Cruz P,Jones FS,Levin J

    更新日期:1976-06-01 00:00:00

  • Functional mapping of anti-factor IX inhibitors developed in patients with severe hemophilia B.

    abstract::Development of inhibitory antibodies is a serious complication of treatment with repeated factor IX infusions in a minority of patients with hemophilia B. Such antibodies detected in 8 patients have been characterized. Typing studies revealed that patients' immune response toward factor IX is highly heterogeneous and ...


    pub_type: 杂志文章


    authors: Christophe OD,Lenting PJ,Cherel G,Boon-Spijker M,Lavergne JM,Boertjes R,Briquel ME,de Goede-Bolder A,Goudemand J,Gaillard S,d'Oiron R,Meyer D,Mertens K

    更新日期:2001-09-01 00:00:00

  • EBV-tissue positive primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity.

    abstract::Primary central nervous system lymphoma (PCNSL) is confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. Rarely, PCNSL occurs in the context of immunosuppression, e.g. post-transplant lymphoproliferative disorders (PTLD) or HIV (AIDS-related PCNSL). These cases are poorly characteri...


    pub_type: 杂志文章


    authors: Gandhi MK,Hoang T,Law SC,Brosda S,O'Rourke K,Tobin JWD,Vari F,Murigneux V,Fink JL,Gunawardana J,Gould CM,Oey H,Bednarska K,Delecluse S,Trappe RU,de Long LM,Sabdia MB,Bhagat G,Hapgood G,Blyth E,Clancy LE,Wight J

    更新日期:2020-11-17 00:00:00

  • Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood.

    abstract::A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% ...


    pub_type: 杂志文章


    authors: Carmel R,Tatsis B,Baril L

    更新日期:1977-06-01 00:00:00

  • Viral, immunologic, and clinical features of primary effusion lymphoma.

    abstract::Primary effusion lymphoma (PEL) is an aggressive HIV-associated lymphoma with a relatively poor prognosis in the era of effective HIV therapy. Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent, and ∼80% of tumors are coinfected with Epstein-Barr virus (EBV). A better understanding of how KSHV-related immune dys...


    pub_type: 杂志文章


    authors: Lurain K,Polizzotto MN,Aleman K,Bhutani M,Wyvill KM,Gonçalves PH,Ramaswami R,Marshall VA,Miley W,Steinberg SM,Little RF,Wilson W,Filie AC,Pittaluga S,Jaffe ES,Whitby D,Yarchoan R,Uldrick TS

    更新日期:2019-04-18 00:00:00

  • Compartmentalization of cyclic GMP-dependent protein kinase in formyl-peptide stimulated neutrophils.

    abstract::The presence and physiologic role of cyclic GMP-dependent protein kinase (G-kinase) in human neutrophils was investigated by Western blot analysis and immunocytochemistry. Small quantities of G-kinase were found in the cytoskeletal-enriched fraction of neutrophil lysates as detected by Western blots using a polyclonal...


    pub_type: 杂志文章


    authors: Pryzwansky KB,Wyatt TA,Nichols H,Lincoln TM

    更新日期:1990-08-01 00:00:00

  • Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95-01.

    abstract::In a prospective trial in 284 children with B-lineage acute lymphoblastic leukemia (ALL), we assessed the clinical utility of real-time quantitative polymerase chain reaction analysis of antigen receptor gene rearrangements for detection of minimal residual disease (MRD) to identify children at high risk of relapse. A...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Zhou J,Goldwasser MA,Li A,Dahlberg SE,Neuberg D,Wang H,Dalton V,McBride KD,Sallan SE,Silverman LB,Gribben JG,Dana-Farber Cancer Institute ALL Consortium.

    更新日期:2007-09-01 00:00:00

  • High level engraftment of NOD/SCID mice by primitive normal and leukemic hematopoietic cells from patients with chronic myeloid leukemia in chronic phase.

    abstract::We have previously shown that intravenously injected peripheral blood (PB) or bone marrow (BM) cells from newly diagnosed chronic myeloid leukemia (CML) patients can engraft the BM of sublethally irradiated severe combined immunodeficient (SCID) mice. We now report engraftment results for chronic phase CML cells in no...


    pub_type: 杂志文章


    authors: Wang JC,Lapidot T,Cashman JD,Doedens M,Addy L,Sutherland DR,Nayar R,Laraya P,Minden M,Keating A,Eaves AC,Eaves CJ,Dick JE

    更新日期:1998-04-01 00:00:00

  • A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis.

    abstract::We have previously shown that G-CSF-deficient (G-CSF(-/-)) mice are markedly protected from collagen-induced arthritis (CIA), which is the major murine model of rheumatoid arthritis, and now investigate the mechanisms by which G-CSF can promote inflammatory disease. Serum G-CSF levels were significantly elevated durin...


    pub_type: 杂志文章


    authors: Eyles JL,Hickey MJ,Norman MU,Croker BA,Roberts AW,Drake SF,James WG,Metcalf D,Campbell IK,Wicks IP

    更新日期:2008-12-15 00:00:00

  • Observations on the binding and interaction of radioiodinated colony-stimulating factor with murine bone marrow cells in vivo.

    abstract::Radioiodinated L-cell-derived colony-stimulating factor (CSF) was used to characterize the binding reaction to murine bone marrow cells. The major increment in cell-associated radioactivity occurred over 24 hr incubation at 37 degrees C, but virtually no binding was observed at 4 degrees C. The reaction was saturable ...


    pub_type: 杂志文章


    authors: Pigoli G,Waheed A,Shadduck RK

    更新日期:1982-02-01 00:00:00

  • Hypoxic induction of gene expression in chronic granulomatous disease-derived B-cell lines: oxygen sensing is independent of the cytochrome b558-containing nicotinamide adenine dinucleotide phosphate oxidase.

    abstract::Reduced oxygenation of a variety of cells results in transcriptional upregulation of several genes, including the hematopoietic hormone erythropoietin, the angiogenic vascular endothelial growth factor (VEGF), and glycolytic enzymes such as aldolase. Recently, the heme protein cytochrome b558 of the nicotinamide adeni...


    pub_type: 杂志文章


    authors: Wenger RH,Marti HH,Schuerer-Maly CC,Kvietikova I,Bauer C,Gassmann M,Maly FE

    更新日期:1996-01-15 00:00:00

  • LDL receptor cooperates with LDL receptor-related protein in regulating plasma levels of coagulation factor VIII in vivo.

    abstract::Low-density lipoprotein (LDL) receptor (LDLR) and LDLR-related protein (LRP) are members of the LDLR family of endocytic receptors. LRP recognizes a wide spectrum of structurally and functionally unrelated ligands, including coagulation factor VIII (FVIII). In contrast, the ligand specificity of LDLR is restricted to ...


    pub_type: 杂志文章


    authors: Bovenschen N,Mertens K,Hu L,Havekes LM,van Vlijmen BJ

    更新日期:2005-08-01 00:00:00

  • Principles of blood separation and component extraction in a disposable continuous-flow single-stage channel.

    abstract::A single-stage disposable channel and seal that provides for leukocyte and granulocyte collection by continuous-flow cell separation (CFCS) has been designed by the IBM Corporation. This paper describes (1) the separation characteristics of whole blood as it responds to varying gravitational (G) forces and flow rates ...


    pub_type: 杂志文章


    authors: Hester JP,Kellogg RM,Mulzet AP,Kruger VR,McCredie KB,Freireich EJ

    更新日期:1979-07-01 00:00:00

  • Microbiologically documented infections and infection-related mortality in children with acute myeloid leukemia.

    abstract::The primary objective was to describe the prevalence and characteristics of microbiologically defined infections and infection-related mortality (IRM) in 492 children with acute myeloid leukemia enrolled on CCG 2961. Secondary objectives were to determine the relationship between demographic, disease-related, and ther...


    pub_type: 杂志文章,多中心研究


    authors: Sung L,Lange BJ,Gerbing RB,Alonzo TA,Feusner J

    更新日期:2007-11-15 00:00:00

  • Steady-state generation of mucosal IgA+ plasmablasts is not abrogated by B-cell depletion therapy with rituximab.

    abstract::The anti-CD20 antibody rituximab depletes human B cells from peripheral blood, but it remains controversial to what extent tissue-resident B cells are affected. In representative patients with rheumatoid arthritis, we here demonstrate that recently activated presumably short-lived plasmablasts expressing HLA-DR(high) ...


    pub_type: 杂志文章


    authors: Mei HE,Frölich D,Giesecke C,Loddenkemper C,Reiter K,Schmidt S,Feist E,Daridon C,Tony HP,Radbruch A,Dörner T

    更新日期:2010-12-09 00:00:00

  • An important role of lymphatic vessel activation in limiting acute inflammation.

    abstract::In contrast to the established role of blood vessel remodeling in inflammation, the biologic function of the lymphatic vasculature in acute inflammation has remained less explored. We studied 2 established models of acute cutaneous inflammation, namely, oxazolone-induced delayed-type hypersensitivity reactions and ult...


    pub_type: 杂志文章


    authors: Huggenberger R,Siddiqui SS,Brander D,Ullmann S,Zimmermann K,Antsiferova M,Werner S,Alitalo K,Detmar M

    更新日期:2011-04-28 00:00:00

  • Changes of DNA methylation and chromatin structure in the human myeloperoxidase gene during myeloid differentiation.

    abstract::Expression of the myeloperoxidase (MPO) gene is tightly regulated in a tissue- and development-specific manner. Accumulation of MPO messenger RNA (mRNA) occurs only at the late myeloblastic and promyelocytic stages of myeloid differentiation and is negligible at other stages of myeloid development and in other tissues...


    pub_type: 杂志文章


    authors: Lübbert M,Miller CW,Koeffler HP

    更新日期:1991-07-15 00:00:00

  • Intrathymic progenitor cell transplantation across histocompatibility barriers results in the persistence of early thymic progenitors and T-cell differentiation.

    abstract::Donor hematopoietic stem cells (HSCs) can correct T-cell deficiencies in patients with severe combined immunodeficiency by replacing resident thymus cells. However, as those progenitors that naturally migrate to the thymus are not capable of supporting long-term thymopoiesis, a successful transplant is thought to requ...


    pub_type: 杂志文章


    authors: de Barros SC,Vicente R,Chebli K,Jacquet C,Zimmermann VS,Taylor N

    更新日期:2013-03-14 00:00:00

  • Complete allogeneic hematopoietic chimerism achieved by a combined strategy of in utero hematopoietic stem cell transplantation and postnatal donor lymphocyte infusion.

    abstract::In utero hematopoietic stem cell transplantation (IUHSCTx) can achieve mixed hematopoietic chimerism and donor-specific tolerance without cytoreductive conditioning or immunosuppression. The primary limitation to the clinical application of IUHSCTx has been minimal donor cell engraftment, well below therapeutic levels...


    pub_type: 杂志文章


    authors: Hayashi S,Peranteau WH,Shaaban AF,Flake AW

    更新日期:2002-08-01 00:00:00

  • Targeting neovascularization in GVHD.

    abstract::In this issue of Blood, Leonhardt et al report that neovascularization during graft-versus-host disease (GVHD) is regulated by av integrins and the micro RNA miR-100. ...


    pub_type: 评论,杂志文章


    authors: Komanduri KV

    更新日期:2013-04-25 00:00:00

  • Platelet-associated complement C3 in immune thrombocytopenic purpura.

    abstract::Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associated IgG (PA-IgG) levels were also m...


    pub_type: 杂志文章


    authors: Myers TJ,Kim BK,Steiner M,Baldini MG

    更新日期:1982-05-01 00:00:00

  • Plasma from patients with idiopathic and human immunodeficiency virus-associated thrombotic thrombocytopenic purpura induces apoptosis in microvascular endothelial cells.

    abstract::The pathogenesis of thrombotic thrombocytopenic purpura (TTP) is obscure. It is manifested classically by platelet thrombi and localized microvascular endothelial cell (EC) proliferation, in the absence of an inflammatory response. It is statistically associated with human retroviral disease, but pathological studies ...


    pub_type: 杂志文章


    authors: Laurence J,Mitra D,Steiner M,Staiano-Coico L,Jaffe E

    更新日期:1996-04-15 00:00:00

  • Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis.

    abstract::Perforin (pfp) and interferon-gamma (IFN-gamma) together in C57BL/6 (B6) and BALB/c mouse strains provided optimal protection in 3 separate tumor models controlled by innate immunity. Using experimental (B6, RM-1 prostate carcinoma) and spontaneous (BALB/c, DA3 mammary carcinoma) models of metastatic cancer, mice defi...


    pub_type: 杂志文章


    authors: Street SE,Cretney E,Smyth MJ

    更新日期:2001-01-01 00:00:00

  • Identification of 15 different candidate causal point mutations and three polymorphisms in 19 patients with protein S deficiency using a scanning method for the analysis of the protein S active gene.

    abstract::To screen for point mutations causing protein S deficiency, we used a sequence of techniques specifically for the study of the protein S active gene, PS alpha. This strategy comprises amplification of exons and intron/exon junctions by means of the polymerase chain reaction (PCR) and electrophoresis of the amplified f...


    pub_type: 杂志文章


    authors: Gandrille S,Borgel D,Eschwege-Gufflet V,Aillaud M,Dreyfus M,Matheron C,Gaussem P,Abgrall JF,Jude B,Sie P

    更新日期:1995-01-01 00:00:00

  • Autoreactive MZ and B-1 B-cell activation by Faslpr is coincident with an increased frequency of apoptotic lymphocytes and a defect in macrophage clearance.

    abstract::Murine autoreactive anti-Smith (Sm) B cells are negatively regulated by anergy and developmental arrest, but are also positively selected into the marginal zone (MZ) and B-1 B-cell populations. Despite positive selection, anti-Sm production occurs only in autoimmune-prone mice. To investigate autoreactive B-cell activ...


    pub_type: 杂志文章


    authors: Qian Y,Conway KL,Lu X,Seitz HM,Matsushima GK,Clarke SH

    更新日期:2006-08-01 00:00:00

  • Biphenotypic B-lymphoid/myeloid cells expressing low levels of Pax5: potential targets of BAL development.

    abstract::The expression of Pax5 commits common lymphoid progenitor cells to B-lymphoid lineage differentiation. Little is known of possible variations in the levels of Pax5 expression and their influences on hematopoietic development. We have developed a retroviral transduction system that allows for the study of possible inte...


    pub_type: 杂志文章


    authors: Simmons S,Knoll M,Drewell C,Wolf I,Mollenkopf HJ,Bouquet C,Melchers F

    更新日期:2012-11-01 00:00:00

  • Establishment and characterization of a novel acute promyelocytic leukemia cell line (UF-1) with retinoic acid-resistant features.

    abstract::All-trans retinoic acid (RA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL). Nevertheless, most of these patients develop RA resistance and relapse. The mechanisms of RA resistance by APL cells are still unclear. To understand the characteristics of human leukemia, ...


    pub_type: 杂志文章


    authors: Kizaki M,Matsushita H,Takayama N,Muto A,Ueno H,Awaya N,Kawai Y,Asou H,Kamada N,Ikeda Y

    更新日期:1996-09-01 00:00:00

  • Development of T3/T cell receptor gene expression in human pre-T neoplasms.

    abstract::Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation....


    pub_type: 杂志文章


    authors: Pittaluga S,Uppenkamp M,Cossman J

    更新日期:1987-04-01 00:00:00