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1.
Cell Stem Cell ; 25(5): 639-653.e7, 2019 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-31631013

RESUMEN

Cellular stress responses serve as crucial decision points balancing persistence or culling of hematopoietic stem cells (HSCs) for lifelong blood production. Although strong stressors cull HSCs, the linkage between stress programs and self-renewal properties that underlie human HSC maintenance remains unknown, particularly at quiescence exit when HSCs must also dynamically shift metabolic state. Here, we demonstrate distinct wiring of the sphingolipidome across the human hematopoietic hierarchy and find that genetic or pharmacologic modulation of the sphingolipid enzyme DEGS1 regulates lineage differentiation. Inhibition of DEGS1 in hematopoietic stem and progenitor cells during the transition from quiescence to cellular activation with N-(4-hydroxyphenyl) retinamide activates coordinated stress pathways that coalesce on endoplasmic reticulum stress and autophagy programs to maintain immunophenotypic and functional HSCs. Thus, our work identifies a linkage between sphingolipid metabolism, proteostatic quality control systems, and HSC self-renewal and provides therapeutic targets for improving HSC-based cellular therapeutics.

2.
Blood ; 133(20): 2198-2211, 2019 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-30796022

RESUMEN

There is a growing body of evidence that the molecular properties of leukemia stem cells (LSCs) are associated with clinical outcomes in acute myeloid leukemia (AML), and LSCs have been linked to therapy failure and relapse. Thus, a better understanding of the molecular mechanisms that contribute to the persistence and regenerative potential of LSCs is expected to result in the development of more effective therapies. We therefore interrogated functionally validated data sets of LSC-specific genes together with their known protein interactors and selected 64 candidates for a competitive in vivo gain-of-function screen to identify genes that enhanced stemness in human cord blood hematopoietic stem and progenitor cells. A consistent effect observed for the top hits was the ability to restrain early repopulation kinetics while preserving regenerative potential. Overexpression (OE) of the most promising candidate, the orphan gene C3orf54/INKA1, in a patient-derived AML model (8227) promoted the retention of LSCs in a primitive state manifested by relative expansion of CD34+ cells, accumulation of cells in G0, and reduced output of differentiated progeny. Despite delayed early repopulation, at later times, INKA1-OE resulted in the expansion of self-renewing LSCs. In contrast, INKA1 silencing in primary AML reduced regenerative potential. Mechanistically, our multidimensional confocal analysis found that INKA1 regulates G0 exit by interfering with nuclear localization of its target PAK4, with concomitant reduction of global H4K16ac levels. These data identify INKA1 as a novel regulator of LSC latency and reveal a link between the regulation of stem cell kinetics and pool size during regeneration.


Asunto(s)
Regulación Leucémica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/genética , Leucemia Mieloide Aguda/genética , Células Madre Neoplásicas/metabolismo , Animales , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Femenino , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Ratones Endogámicos NOD , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/patología , Regulación hacia Arriba , Quinasas p21 Activadas/análisis
3.
Exp Hematol ; 59: 51-59.e1, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29225194

RESUMEN

GPR56 molecule, a G-protein-coupled receptor, was suggested to be expressed in mouse hematopoietic stem cells (HSCs) by gene expression analyses. However, little is known about the cell surface expression of GPR56 protein in mouse HSCs due to the absence of an appropriate monoclonal antibody against GPR56 for flow cytometry analyses. In the present study, we established a novel monoclonal antibody against mouse GPR56 (57R2A) to examine the expression and distribution of GPR56 protein in HSCs. A flow cytometry analysis using 57R2A showed that GPR56 was highly expressed in the CD34-, c-Kit+, Sca-1+, lineage-negative (Lin-) fraction, which are highly enriched with HSCs. The competitive long-term repopulation (LTR) assay showed that LTR cells were included only within the GPR56+ fraction (≤15%) of bone marrow mononuclear cells (BMMNCs), but not within the remaining GPR56- fraction (85%), suggesting that all HSCs express GPR56 protein on their surface. Furthermore, we showed that double staining of BMMNCs with only 57R2A and AMM2 (monoclonal antibody against the HSC marker MPL) enabled enrichment of all LTR cells in the double-positive fraction (0.8% of BMMNCs), within which the LTR potency was consistent with the expression of both GPR56 and MPL. In conclusion, these findings for 57R2A suggest that all HSCs in mouse BMMNCs express GPR56 protein on their surface and that GPR56 is a positive marker for HSCs.


Asunto(s)
Anticuerpos Monoclonales , Regulación de la Expresión Génica/inmunología , Células Madre Hematopoyéticas , Receptores Acoplados a Proteínas G , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Femenino , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/metabolismo , Ratones , Ratas , Ratas Endogámicas F344 , Receptores Acoplados a Proteínas G/biosíntesis , Receptores Acoplados a Proteínas G/inmunología
4.
Nat Genet ; 48(12): 1481-1489, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27776115

RESUMEN

Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL). Here we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion. ERGalt uses a non-canonical first exon whose transcription was initiated by DUX4 binding. ERGalt retains the DNA-binding and transactivation domains of ERG, but it inhibits wild-type ERG transcriptional activity and is transforming. These results illustrate a unique paradigm of transcription factor deregulation in leukemia in which DUX4 deregulation results in loss of function of ERG, either by deletion or induced expression of an isoform that is a dominant-negative inhibitor of wild-type ERG function.


Asunto(s)
Transformación Celular Neoplásica/genética , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica , Reordenamiento Génico , Proteínas de Homeodominio/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Transformación Celular Neoplásica/patología , Perfilación de la Expresión Génica , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Isoformas de Proteínas , Regulador Transcripcional ERG/genética , Adulto Joven
5.
Cell Stem Cell ; 17(3): 341-52, 2015 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-26279267

RESUMEN

Signaling mechanisms underlying self-renewal of leukemic stem cells (LSCs) are poorly understood, and identifying pathways specifically active in LSCs could provide opportunities for therapeutic intervention. T-cell immunoglobin mucin-3 (TIM-3) is expressed on the surface of LSCs in many types of human acute myeloid leukemia (AML), but not on hematopoietic stem cells (HSCs). Here, we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for LSC self-renewal and development of human AML. Serum Gal-9 levels were significantly elevated in AML patients and in mice xenografted with primary human AML samples, and neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML. Gal-9-mediated stimulation of TIM-3 co-activated NF-κB and ß-catenin signaling, pathways known to promote LSC self-renewal. These changes were further associated with leukemic transformation of a variety of pre-leukemic disorders and together highlight that targeting the TIM-3/Gal-9 autocrine loop could be a useful strategy for treating myeloid leukemias.


Asunto(s)
Comunicación Autocrina , Progresión de la Enfermedad , Galectinas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Proteínas de la Membrana/metabolismo , Células Madre Neoplásicas/patología , Adulto , Animales , Anticuerpos Antineoplásicos/metabolismo , Antígenos CD34/metabolismo , Crisis Blástica/sangre , Crisis Blástica/patología , Línea Celular Transformada , Núcleo Celular/metabolismo , Proliferación Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Galectinas/sangre , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/inmunología , Ligandos , Ratones , Modelos Biológicos , FN-kappa B/metabolismo , Células Madre Neoplásicas/metabolismo , Fosforilación , Unión Proteica , Transporte de Proteínas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Carga Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/metabolismo
6.
Cell Stem Cell ; 7(6): 708-17, 2010 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-21112565

RESUMEN

Acute myeloid leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), an ultimate therapeutic target for AML. Here we identified T cell immunoglobulin mucin-3 (TIM-3) as a surface molecule expressed on LSCs in most types of AML except for acute promyelocytic leukemia, but not on normal hematopoietic stem cells (HSCs). TIM-3(+) but not TIM-3⁻ AML cells reconstituted human AML in immunodeficient mice, suggesting that the TIM-3(+) population contains most, if not all, of functional LSCs. We established an anti-human TIM-3 mouse IgG2a antibody having complement-dependent and antibody-dependent cellular cytotoxic activities. This antibody did not harm reconstitution of normal human HSCs, but blocked engraftment of AML after xenotransplantation. Furthermore, when it is administered into mice grafted with human AML, this treatment dramatically diminished their leukemic burden and eliminated LSCs capable of reconstituting human AML in secondary recipients. These data suggest that TIM-3 is one of the promising targets to eradicate AML LSCs.


Asunto(s)
Leucemia Mieloide Aguda/tratamiento farmacológico , Proteínas de la Membrana/antagonistas & inhibidores , Células Madre Neoplásicas/efectos de los fármacos , Adulto , Animales , Anticuerpos/uso terapéutico , Linaje de la Célula , Hematopoyesis , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Inmunoglobulina G/inmunología , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones SCID , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/metabolismo , Trasplante Heterólogo
7.
Blood ; 113(6): 1250-6, 2009 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-18945958

RESUMEN

Hematopoietic stem cells (HSCs) reside in a bone marrow niche in a nondividing state from which they occasionally are aroused to undergo cell division. Yet, the mechanism underlying this unique feature remains largely unknown. We have recently shown that freshly isolated CD34-KSL hematopoietic stem cells (HSCs) in a hibernation state exhibit inhibited lipid raft clustering. Lipid raft clustering induced by cytokines is essential for HSCs to augment cytokine signals to the level enough to re-enter the cell cycle. Here we screened candidate niche signals that inhibit lipid raft clustering, and identified that transforming growth factor-beta (TGF-beta) efficiently inhibits cytokine-mediated lipid raft clustering and induces HSC hibernation ex vivo. Smad2 and Smad3, the signaling molecules directly downstream from and activated by TGF-beta receptors were specifically activated in CD34-KSL HSCs in a hibernation state, but not in cycling CD34+KSL progenitors. These data uncover a critical role for TGF-beta as a candidate niche signal in the control of HSC hibernation and provide TGF-beta as a novel tool for ex vivo modeling of the HSC niche.


Asunto(s)
Médula Ósea/metabolismo , Citocinas/farmacología , Células Madre Hematopoyéticas/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Antígenos CD34/metabolismo , Diferenciación Celular , Células Cultivadas , Técnica del Anticuerpo Fluorescente , Lípidos , Microdominios de Membrana/fisiología , Ratones , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/genética
8.
Blood ; 111(4): 1903-12, 2008 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-18042804

RESUMEN

Interleukin (IL)-27, one of the most recently discovered IL-6 family cytokines, activates both the signal transducer and activator of transcription (STAT)1 and STAT3, and plays multiple roles in pro- and anti-inflammatory immune responses. IL-27 acts on various types of cells including T, B, and macrophage through the common signal-transducing receptor gp130 and its specific receptor WSX-1, but the effect of IL-27 on hematopoietic stem cells (HSCs) remains unknown. Here, we show that IL-27 together with stem cell factor (SCF) directly acts on HSCs and supports their early differentiation in vitro and in vivo. CD34(-/low)c-Kit(+)Sca-1(+)lineage marker(-) (CD34(-)KSL) cells, a population highly enriched in mouse HSCs, were found to express both IL-27 receptor subunits. In vitro cultures of CD34(-)KSL cells with IL-27 and SCF resulted in an expansion of progenitors including short-term repopulating cells, while some of their long-term repopulating activity also was maintained. To examine its in vivo effect, transgenic mice expressing IL-27 were generated. These mice exhibited enhanced myelopoiesis and impaired B lymphopoiesis in the bone marrow with extramedullary hematopoiesis in the spleen. Moreover, IL-27 similarly acted on human CD34(+) cells. These results suggest that IL-27 is one of the limited cytokines that play a role in HSC regulation.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Células Madre Hematopoyéticas/citología , Interleucinas/farmacología , Animales , Antígenos CD34/análisis , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Cartilla de ADN , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/genética , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Ratones , Proteínas Recombinantes/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
9.
EMBO J ; 25(15): 3515-23, 2006 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-16858398

RESUMEN

Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) niche in a noncycling state and enter the cell cycle at long intervals. However, little is known about inter- and intracellular signaling mechanisms underlying this unique property of HSCs. Here, we show that lipid raft clustering is a key event in the regulation of HSC dormancy. Freshly isolated HSCs from the BM niche lack lipid raft clustering, exhibit repression of the AKT-FOXO signaling pathway, and express abundant p57(Kip2) cyclin-dependent kinase inhibitor. Lipid raft clustering induced by cytokines is essential for HSC re-entry into the cell cycle. Conversely, inhibition of lipid raft clustering caused sustained nuclear accumulation of FOXO transcription factors and induced HSC hibernation ex vivo. These data establish a critical role for lipid rafts in regulating the cell cycle, the survival, and the entry into apoptosis of HSCs and uncover a striking similarity in HSC hibernation and Caenorhabditis elegans dauer formation.


Asunto(s)
Citocinas/farmacología , Células Madre Hematopoyéticas/metabolismo , Microdominios de Membrana/fisiología , Transducción de Señal , Animales , Apoptosis , Caenorhabditis elegans/crecimiento & desarrollo , Ciclo Celular/fisiología , Células Cultivadas , Técnica del Anticuerpo Fluorescente , Células Madre Hematopoyéticas/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Células Madre
10.
Development ; 133(14): 2771-9, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16794034

RESUMEN

Vasculogenesis and hematopoiesis are thought to arise in hemangioblasts, the common progenitors of cells in vessels and in blood. This scheme was challenged by kinetic analysis of vascular endothelial and hematopoietic progenitors in early gastrulating mouse embryos. The OP-9 co-culture system with a combination of cytokines permitted the detection of endothelial progenitors, as well as stroma-dependent hematopoietic progenitors. Endothelial progenitors were detected as early as embryonic day (E) 5.50, after which time their numbers increased. Stroma-dependent hematopoietic progenitors were detected at E6.75, the time point when hemangioblasts reportedly emerge. Colony-forming units in culture (CFU-c), most likely generated from stroma-dependent hematopoietic progenitors via contact with the microenvironment, were detected at E7.50, concomitant with the onset of primitive hematopoiesis in the yolk sac. The presence of nucleated erythrocytes and the expression of an embryonic-type globin in erythroid colonies derived from stroma-dependent hematopoietic progenitors and from CFU-c support the notion that these progenitors coordinately establish primitive hematopoiesis. Using Oct3/4 promoter-driven GFP transgenic mice, early endothelial progenitors, stroma-dependent hematopoietic progenitors, and CFU-c were all shown to express the Oct3/4 transcription factor. Among Oct3/4-positive cells, both endothelial and hematopoietic progenitors were present in the CD31-positive fraction, leaving a subset of endothelial progenitors in the CD31-negative fraction. These data imply that Oct3/4-positive mesoderm gives rise to CD31-negative angioblasts, CD31-positive angiboblasts and CD31-positive hemangioblasts. We propose a distinct developmental pathway in which the angioblast lineage directly diverges from mesoderm prior to and independent of hemangioblast development.


Asunto(s)
Diferenciación Celular/fisiología , Embrión de Mamíferos , Células Endoteliales/fisiología , Endotelio Vascular , Hematopoyesis/fisiología , Células Madre/fisiología , Animales , Biomarcadores/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Embrión de Mamíferos/anatomía & histología , Embrión de Mamíferos/fisiología , Células Endoteliales/citología , Endotelio Vascular/citología , Endotelio Vascular/embriología , Femenino , Edad Gestacional , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Células Madre/citología
11.
Blood ; 107(11): 4317-25, 2006 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-16455951

RESUMEN

Using an in silico database search, we identified a novel gene encoding a cell surface molecule with a thrombospondin domain, and designated the gene as transmembrane molecule with thrombospondin module (Tmtsp). Expression profiling of Tmtsp using specific monoclonal antibodies and Venus, a variant of yellow fluorescent protein knock-in mice in the Tmtsp locus, demonstrated its specific expression in hematopoietic and endothelial cells. In lymphohematopoietic cells, Tmtsp was predominantly expressed in hematopoietic stem and progenitor cells, and the level of expression gradually declined as the cells differentiated. Venus expression faithfully traced the expression of Tmtsp, and the level of Venus expression correlated well to the in vitro hematopoietic activity as well as the in vivo bone marrow repopulating capacity. Notably, Venus expression marked the development of definitive hematopoiesis in both the extraembryonic yolk sac and the intraembryonic aorta-gonad-mesonephros (AGM) region and, in combination with CD41, strikingly promoted the enrichment of developing progenitors in the CD41(+)Venus(high) fraction at embryonic day 10.5 (E10.5). In this context, Tmtsp is a novel marker gene for primitive hematopoietic cells and endothelial cells, and Tmtsp(Venus/)(+) mice would serve as a valuable mouse model for the analysis of both embryonic and adult hematopoiesis, as well as for vascular biology.


Asunto(s)
Células Endoteliales/química , Células Madre Hematopoyéticas/química , Trombospondinas/genética , Secuencia de Aminoácidos , Animales , Médula Ósea/fisiología , Embrión de Mamíferos/citología , Biblioteca de Genes , Marcadores Genéticos , Hematopoyesis , Humanos , Proteínas de la Membrana , Ratones , Datos de Secuencia Molecular , Bazo , Trombospondina 1/análisis , Trombospondina 1/química , Trombospondina 1/genética , Trombospondinas/análisis , Trombospondinas/química , Distribución Tisular
12.
J Exp Ther Oncol ; 4(3): 239-46, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15724843

RESUMEN

Human ATP-binding cassette (ABC) transporter genes are classified into seven sub-families, where "C" subfamily comprises a total of 13 gene members. The ABCC10 cDNA was cloned in the human full-length cDNA project at the Kazusa DNA Research Institute. However, current information is limited regarding its physiological function and gene expression. In the present study, we have investigated the expression of the ABCC10 gene to gain insight into its biological nature. By quantitative PCR, ABCC10 gene expression is demonstrated to be highest in pancreas among the adult and fetal tissues and tumors presently tested. Decreased expression was observed when resting T- and B-cells were activated. Furthermore, when we examined its expression under apoptotic conditions, we found that ABCC10 mRNA levels remarkably increased in doxorubicin-treated MCF7 cells, whereas its up-regulation was suppressed in p53-dominant-negative MCF7 cells. These results suggest that expression of the ABCC10 gene is regulated in a p53-dependent manner during DNA-damage-related apoptosis.


Asunto(s)
Apoptosis , Daño del ADN , Perfilación de la Expresión Génica , Genes p53 , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Antibióticos Antineoplásicos/farmacología , Doxorrubicina/farmacología , Desarrollo Fetal , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Reacción en Cadena de la Polimerasa , Transducción de Señal , Células Tumorales Cultivadas , Regulación hacia Arriba
13.
J Exp Ther Oncol ; 3(3): 136-46, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14641820

RESUMEN

The human ABCC1 gene, a member of the ATP-binding cassette transporter super-family, plays a critical role in conferring cancer cell resistance to chemotherapeutic drugs. In the present study, we have cloned the full-length cDNA of rat Abcc1 and evaluated its significance in drug resistance. Analysis using the currently available genome database revealed that the rat Abcc1 gene is located on rat chromosome 13 and consists of at least 30 exons. The rat Abcc1 cDNA cloned from the spleen was 4981-bp long, within which two additional splicing variants were discovered. The rat Abcc1 gene is expressed in a wide variety of organs, with the highest expression being observed in the spleen. Human embryonic kidney 293 cells were transfected with the rat Abcc1/pcDNA3.1 vector to stably express rat Abcc1. Overexpression of rat Abcc1 elicited high resistance to etoposide. In contrast to the hitherto known drug-resistance profile of human ABCC1, rat Abcc1 did not significantly confer cellular resistance to anthracyclins or Vinca alkaloids. Our results strongly suggest that there is a significant species difference between human ABCC1 and rat Abcc1 in their contribution to the drug-resistance profile.


Asunto(s)
Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Secuencia de Aminoácidos , Animales , Antineoplásicos/farmacología , Línea Celular/efectos de los fármacos , Clonación Molecular , ADN Complementario/genética , Resistencia a Múltiples Medicamentos , Humanos , Riñón/citología , Ratones , Datos de Secuencia Molecular , Ratas , Alineación de Secuencia , Especificidad de la Especie , Transfección
14.
Biochem Biophys Res Commun ; 299(3): 410-7, 2002 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-12445816

RESUMEN

In the present study, we have cloned the cDNA of ABCC13, a novel ABC transporter, from the cDNA library of adult human placenta. The ABCC13 gene spans approximately 70kb on human chromosome 21q11.2 and consists of 14 exons. The open reading frame of the ABCC13 cDNA encodes a peptide consisting of 325 amino acid residues. The amino acid sequence corresponding to putative membrane-spanning domains was remarkably similar to ABCC1, ABCC2, ABCC3, and ABCC6. The ABCC13 gene was expressed in the fetal liver at the highest level among the organs studied. While ABCC13 was expressed in the bone marrow, its expression in peripheral blood leukocytes of adult humans was much lower and no detectable levels were observed in differentiated hematopoietic cells. The expression of ABCC13 in K562 cells decreased during cell differentiation induced by TPA. These results suggest that the expression of human ABCC13 is related with hematopoiesis.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Feto/fisiología , Hígado/fisiología , Transportadoras de Casetes de Unión a ATP/química , Transportadoras de Casetes de Unión a ATP/genética , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Células Cultivadas , Cromosomas Humanos Par 21 , Clonación Molecular , Exones , Feto/anatomía & histología , Biblioteca de Genes , Humanos , Intrones , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Placenta/fisiología , Alineación de Secuencia , Distribución Tisular
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