Yasui K et al. (JAN 2003)
Stem cells (Dayton,Ohio) 21 2 143--51
Differences between peripheral blood and cord blood in the kinetics of lineage-restricted hematopoietic cells: implications for delayed platelet recovery following cord blood transplantation.
Cord blood (CB) cells are a useful source of hematopoietic cells for transplantation. The hematopoietic activities of CB cells are different from those of bone marrow and peripheral blood (PB) cells. Platelet recovery is significantly slower after transplantation with CB cells than with cells from other sources. However,the cellular mechanisms underlying these differences have not been elucidated. We compared the surface marker expression profiles of PB and CB hematopoietic cells. We focused on two surface markers of hematopoietic cell immaturity,i.e.,CD34 and AC133. In addition to differences in surface marker expression,the PB and CB cells showed nonidentical differentiation pathways from AC133(+)CD34(+) (immature) hematopoietic cells to terminally differentiated cells. The majority of the AC133(+)CD34(+) PB cells initially lost AC133 expression and eventually became AC133(-)CD34(-) cells. In contrast,the AC133(+)CD34(+) CB cells did not go through the intermediate AC133(-)CD34(+) stage and lost both markers simultaneously. Meanwhile,the vast majority of megakaryocyte progenitors were of the AC133(-)CD34(+) phenotype. We conclude that the delayed recovery of platelets after CB transplantation is due to both subpopulation distribution and the process of differentiation from AC133(+)CD34(+) cells.
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产品类型：
产品号#：
04064
04960
04902
04900
04961
04901
04963
04962
04970
04971
产品名：
MethoCult™ H4034 Optimum启动试剂盒套装
MegaCult™-C胶原蛋白和不含细胞因子的培养基
胶原蛋白溶液
MegaCult™-C培养基无细胞因子
MegaCult™-C胶原蛋白和细胞因子培养基
MegaCult™-C细胞因子培养基
双室载玻片试剂盒
MegaCult™-C cfu染色试剂盒
MegaCult™-C不含细胞因子完整试剂盒
MegaCult™-C细胞因子完整试剂盒
Moody JL et al. (JUN 2004)
Blood 103 12 4503--10
Anemia, thrombocytopenia, leukocytosis, extramedullary hematopoiesis, and impaired progenitor function in Pten+/-SHIP-/- mice: a novel model of myelodysplasia.
The myeloproliferative disorder of mice lacking the Src homology 2 (SH2)-containing 5' phosphoinositol phosphatase,SHIP,underscores the need for closely regulating phosphatidylinositol 3-kinase (PI3K) pathway activity,and hence levels of phosphatidylinositol species during hematopoiesis. The role of the 3' phosphoinositol phosphatase Pten in this process is less clear,as its absence leads to embryonic lethality. Despite Pten heterozygosity being associated with a lymphoproliferative disorder,we found no evidence of a hematopoietic defect in Pten(+/-) mice. Since SHIP shares the same substrate (PIP(3)) with Pten,we hypothesized that the former might compensate for Pten haploinsufficiency in the marrow. Thus,we examined the effect of Pten heterozygosity in SHIP(-/-) mice,predicting that further dysregulation of PIP(3) metabolism would exacerbate the pheno-type of the latter. Indeed,compared with SHIP(-/-) mice,Pten(+/-)SHIP(-/-) animals developed a myelodysplastic phenotype characterized by increased hepatosplenomegaly,extramedullary hematopoiesis,anemia,and thrombocytopenia. Consistent with a marrow defect,clonogenic assays demonstrated reductions in committed myeloid and megakaryocytic progenitors in these animals. Providing further evidence of a Pten(+/-)SHIP(-/-) progenitor abnormality,reconstitution of irradiated mice with marrows from these mice led to a marked defect in short-term repopulation of peripheral blood by donor cells. These studies suggest that the regulation of the levels and/or ratios of PI3K-derived phosphoinositol species by these 2 phosphatases is critical to normal hematopoiesis.
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产品类型：
产品号#：
04960
04902
04900
04961
04901
04963
04962
04970
04971
产品名：
MegaCult™-C胶原蛋白和不含细胞因子的培养基
胶原蛋白溶液
MegaCult™-C培养基无细胞因子
MegaCult™-C胶原蛋白和细胞因子培养基
MegaCult™-C细胞因子培养基
双室载玻片试剂盒
MegaCult™-C cfu染色试剂盒
MegaCult™-C不含细胞因子完整试剂盒
MegaCult™-C细胞因子完整试剂盒
Fé et al. (MAR 2006)
The Journal of clinical investigation 116 3 715--23
Blocking the alpha 4 integrin-paxillin interaction selectively impairs mononuclear leukocyte recruitment to an inflammatory site.
Antagonists to alpha4 integrin show promise for several autoimmune and inflammatory diseases but may exhibit mechanism-based toxicities. We tested the capacity of blockade of alpha4 integrin signaling to perturb functions involved in inflammation,while limiting potential adverse effects. We generated and characterized mice bearing a Y991A mutation in alpha4 integrin [alpha4(Y991A) mice],which blocks paxillin binding and inhibits alpha4 integrin signals that support leukocyte migration. In contrast to the embryonic-lethal phenotype of alpha4 integrin-null mice,mice bearing the alpha4(Y991A) mutation were viable and fertile; however,they exhibited defective recruitment of mononuclear leukocytes into thioglycollate-induced peritonitis. Alpha4 integrins are essential for definitive hematopoiesis; however,the alpha4(Y991A) mice had intact lymphohematopoiesis and,with the exception of reduced Peyer's patches,normal architecture and cellularity of secondary lymphoid tissues. We conclude that interference with alpha4 integrin signaling can selectively impair mononuclear leukocyte recruitment to sites of inflammation while sparing vital functions of alpha4 integrins in development and hematopoiesis.
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产品类型：
产品号#：
03434
03444
04960
04902
04900
04963
04962
04970
产品名：
MethoCult™GF M3434
MethoCult™GF M3434
MegaCult™-C胶原蛋白和不含细胞因子的培养基
胶原蛋白溶液
MegaCult™-C培养基无细胞因子
双室载玻片试剂盒
MegaCult™-C cfu染色试剂盒
MegaCult™-C不含细胞因子完整试剂盒
Vodyanik MA et al. (SEP 2006)
Blood 108 6 2095--105
Leukosialin (CD43) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures.
During hematopoietic differentiation of human embryonic stem cells (hESCs),early hematopoietic progenitors arise along with endothelial cells within the CD34(+) population. Although hESC-derived hematopoietic progenitors have been previously identified by functional assays,their phenotype has not been defined. Here,using hESC differentiation in coculture with OP9 stromal cells,we demonstrate that early progenitors committed to hematopoietic development could be identified by surface expression of leukosialin (CD43). CD43 was detected on all types of emerging clonogenic progenitors before expression of CD45,persisted on differentiating hematopoietic cells,and reliably separated the hematopoietic CD34(+) population from CD34(+)CD43(-)CD31(+)KDR(+) endothelial and CD34(+)CD43(-)CD31(-)KDR(-) mesenchymal cells. Furthermore,we demonstrated that the first-appearing CD34(+)CD43(+)CD235a(+)CD41a(+/-)CD45(-) cells represent precommitted erythro-megakaryocytic progenitors. Multipotent lymphohematopoietic progenitors were generated later as CD34(+)CD43(+)CD41a(-)CD235a(-)CD45(-) cells. These cells were negative for lineage-specific markers (Lin(-)),expressed KDR,VE-cadherin,and CD105 endothelial proteins,and expressed GATA-2,GATA-3,RUNX1,C-MYB transcription factors that typify initial stages of definitive hematopoiesis originating from endothelial-like precursors. Acquisition of CD45 expression by CD34(+)CD43(+)CD45(-)Lin(-) cells was associated with progressive myeloid commitment and a decrease of B-lymphoid potential. CD34(+)CD43(+)CD45(+)Lin(-) cells were largely devoid of VE-cadherin and KDR expression and had a distinct FLT3(high)GATA3(low)RUNX1(low)PU1(high)MPO(high)IL7RA(high) gene expression profile.
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产品类型：
产品号#：
04435
04445
04960
04902
04900
产品名：
MethoCult™H4435富集
MethoCult™H4435富集
MegaCult™-C胶原蛋白和不含细胞因子的培养基
胶原蛋白溶液
MegaCult™-C培养基无细胞因子
Xing S et al. (MAY 2008)
Blood 111 10 5109--17
Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice.
The JAK2(V617F) mutation was found in most patients with myeloproliferative disorders (MPDs),including polycythemia vera,essential thrombocythemia,and primary myelofibrosis. We have generated transgenic mice expressing the mutated enzyme in the hematopoietic system driven by a vav gene promoter. The mice are viable and fertile. One line of the transgenic mice,which expressed a lower level of JAK2(V617F),showed moderate elevations of blood cell counts,whereas another line with a higher level of JAK2(V617F) expression displayed marked increases in blood counts and developed phenotypes that closely resembled human essential thrombocythemia and polycythemia vera. The latter line of mice also developed primary myelofibrosis-like symptoms as they aged. The transgenic mice showed erythroid,megakaryocytic,and granulocytic hyperplasia in the bone marrow and spleen,displayed splenomegaly,and had reduced levels of plasma erythropoietin and thrombopoietin. They possessed an increased number of hematopoietic progenitor cells in peripheral blood,spleen,and bone marrow,and these cells formed autonomous colonies in the absence of growth factors and cytokines. The data show that JAK2(V617F) can cause MPDs in mice. Our study thus provides a mouse model to study the pathologic role of JAK2(V617F) and to develop treatment for MPDs.
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产品类型：
产品号#：
03231
03434
03444
04960
04902
04900
04961
04901
04963
04962
04970
04971
产品名：
MethoCult™M3231
MethoCult™GF M3434
MethoCult™GF M3434
MegaCult™-C胶原蛋白和不含细胞因子的培养基
胶原蛋白溶液
MegaCult™-C培养基无细胞因子
MegaCult™-C胶原蛋白和细胞因子培养基
MegaCult™-C细胞因子培养基
双室载玻片试剂盒
MegaCult™-C cfu染色试剂盒
MegaCult™-C不含细胞因子完整试剂盒
MegaCult™-C细胞因子完整试剂盒
Lannutti BJ et al. (FEB 2009)
Blood 113 8 1778--85
Incomplete restoration of Mpl expression in the mpl-/- mouse produces partial correction of the stem cell-repopulating defect and paradoxical thrombocytosis.
Expression of Mpl is restricted to hematopoietic cells in the megakaryocyte lineage and to undifferentiated progenitors,where it initiates critical cell survival and proliferation signals after stimulation by its ligand,thrombopoietin (TPO). As a result,a deficiency in Mpl function in patients with congenital amegakaryocytic thrombocytopenia (CAMT) and in mpl(-/-) mice produces profound thrombocytopenia and a severe stem cell-repopulating defect. Gene therapy has the potential to correct the hematopoietic defects of CAMT by ectopic gene expression that restores normal Mpl receptor activity. We rescued the mpl(-/-) mouse with a transgenic vector expressing mpl from the promoter elements of the 2-kb region of DNA just proximal to the natural gene start site. Transgene rescued mice exhibit thrombocytosis but only partial correction of the stem cell defect. Furthermore,they show very low-level expression of Mpl on platelets and megakaryocytes,and the transgene-rescued megakaryocytes exhibit diminished TPO-dependent kinase phosphorylation and reduced platelet production in bone marrow chimeras. Thrombocytosis is an unexpected consequence of reduced Mpl expression and activity. However,impaired TPO homeostasis in the transgene-rescued mice produces elevated plasma TPO levels,which serves as an unchecked stimulus to drive the observed excessive megakaryocytopoiesis.
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Migliaccio AR et al. (FEB 2003)
The Journal of experimental medicine 197 3 281--96
GATA-1 as a regulator of mast cell differentiation revealed by the phenotype of the GATA-1low mouse mutant.
Here it is shown that the phenotype of adult mice lacking the first enhancer (DNA hypersensitive site I) and the distal promoter of the GATA-1 gene (neo Delta HS or GATA-1(low) mutants) reveals defects in mast cell development. These include the presence of morphologically abnormal alcian blue(+) mast cells and apoptotic metachromatic(-) mast cell precursors in connective tissues and peritoneal lavage and numerous (60-70% of all the progenitors) unique" trilineage cells committed to erythroid�
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产品类型：
产品号#：
04960
04902
04900
04961
04901
04963
04962
04970
04971
产品名：
MegaCult™-C胶原蛋白和不含细胞因子的培养基
胶原蛋白溶液
MegaCult™-C培养基无细胞因子
MegaCult™-C胶原蛋白和细胞因子培养基
MegaCult™-C细胞因子培养基
双室载玻片试剂盒
MegaCult™-C cfu染色试剂盒
MegaCult™-C不含细胞因子完整试剂盒
MegaCult™-C细胞因子完整试剂盒
Wang Q et al. (FEB 2004)
Blood 103 4 1278--85
BUBR1 deficiency results in abnormal megakaryopoiesis.
The physiologic function of BUBR1,a key component of the spindle checkpoint,was examined by generating BUBR1-mutant mice. BUBR1(-/-) embryos failed to survive beyond day 8.5 in utero as a result of extensive apoptosis. Whereas BUBR1(+/-) blastocysts grew relatively normally in vitro,BUBR1(-/-) blastocysts exhibited impaired proliferation and atrophied. Adult BUBR1(+/-) mice manifested splenomegaly and abnormal megakaryopoiesis. BUBR1 haploinsufficiency resulted in an increase in the number of splenic megakaryocytes,which was correlated with an increase in megakaryocytic,but a decrease in erythroid,progenitors in bone marrow cells. RNA interference-mediated down-regulation of BUBR1 also caused an increase in polyploidy formation in murine embryonic fibroblast cells and enhanced megakaryopoiesis in bone marrow progenitor cells. However,enhanced megakaryopoiesis in BUBR1(+/-) mice was not correlated with a significant increase in platelets in peripheral blood,which was at least partly due to a defect in the formation of proplatelet-producing megakaryocytes. Together,these results indicate that BUBR1 is essential for early embryonic development and normal hematopoiesis.
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产品类型：
产品号#：
09600
09650
04960
04902
04900
04961
04901
04963
04962
04970
04971
产品名：
StemSpan™ SFEM
StemSpan™ SFEM
MegaCult™-C胶原蛋白和不含细胞因子的培养基
胶原蛋白溶液
MegaCult™-C培养基无细胞因子
MegaCult™-C胶原蛋白和细胞因子培养基
MegaCult™-C细胞因子培养基
双室载玻片试剂盒
MegaCult™-C cfu染色试剂盒
MegaCult™-C不含细胞因子完整试剂盒
MegaCult™-C细胞因子完整试剂盒
Drayer AL et al. (JAN 2006)
Stem cells (Dayton,Ohio) 24 1 105--14
Mammalian target of rapamycin is required for thrombopoietin-induced proliferation of megakaryocyte progenitors.
Thrombopoietin (TPO) is a potent regulator of megakaryopoiesis and stimulates megakaryocyte (MK) progenitor expansion and MK differentiation. In this study,we show that TPO induces activation of the mammalian target of rapamycin (mTOR) signaling pathway,which plays a central role in translational regulation and is required for proliferation of MO7e cells and primary human MK progenitors. Treatment of MO7e cells,human CD34+,and primary MK cells with the mTOR inhibitor rapamycin inhibits TPO-induced cell cycling by reducing cells in S phase and blocking cells in G0/G1. Rapamycin markedly inhibits the clonogenic growth of MK progenitors with high proliferative capacity but does not reduce the formation of small MK colonies. Addition of rapamycin to MK suspension cultures reduces the number of MK cells,but inhibition of mTOR does not significantly affect expression of glycoproteins IIb/IIIa (CD41) and glycoprotein Ib (CD42),nuclear polyploidization levels,cell size,or cell survival. The downstream effectors of mTOR,p70 S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1),are phosphorylated by TPO in a rapamycin- and LY294002-sensitive manner. Part of the effect of the phosphatidyl inositol 3-kinase pathway in regulating megakaryopoiesis may be mediated by the mTOR/S6K/4E-BP1 pathway. In conclusion,these data demonstrate that the mTOR pathway is activated by TPO and plays a critical role in regulating proliferation of MK progenitors,without affecting differentiation or cell survival.
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产品类型：
产品号#：
04961
04902
04901
04971
04963
04962
产品名：
MegaCult™-C胶原蛋白和细胞因子培养基
胶原蛋白溶液
MegaCult™-C细胞因子培养基
MegaCult™-C细胞因子完整试剂盒
双室载玻片试剂盒
MegaCult™-C cfu染色试剂盒
Matsumura-Takeda K et al. (APR 2007)
Stem cells (Dayton,Ohio) 25 4 862--70
CD41+/CD45+ cells without acetylcholinesterase activity are immature and a major megakaryocytic population in murine bone marrow.
Murine megakaryocytes (MKs) are defined by CD41/CD61 expression and acetylcholinesterase (AChE) activity; however,their stages of differentiation in bone marrow (BM) have not been fully elucidated. In murine lineage-negative (Lin(-))/CD45(+) BM cells,we found CD41(+) MKs without AChE activity (AChE(-)) except for CD41(++) MKs with AChE activity (AChE(+)),in which CD61 expression was similar to their CD41 level. Lin(-)/CD41(+)/CD45(+)/AChE(-) MKs could differentiate into AChE(+),with an accompanying increase in CD41/CD61 during in vitro culture. Both proplatelet formation (PPF) and platelet (PLT) production for Lin(-)/CD41(+)/CD45(+)/AChE(-) MKs were observed later than for Lin(-)/CD41(++)/CD45(+)/AChE(+) MKs,whereas MK progenitors were scarcely detected in both subpopulations. GeneChip and semiquantitative polymerase chain reaction analyses revealed that the Lin(-)/CD41(+)/CD45(+)/AChE(-) MKs are assigned at the stage between the progenitor and PPF preparation phases in respect to the many MK/PLT-specific gene expressions,including beta1-tubulin. In normal mice,the number of Lin(-)/CD41(+)/CD45(+)/AChE(-) MKs was 100 times higher than that of AChE(+) MKs in BM. When MK destruction and consequent thrombocytopenia were caused by an antitumor agent,mitomycin-C,Lin(-)/CD41(+)/CD45(+)/AChE(-) MKs led to an increase in AChE(+) MKs and subsequent PLT recovery with interleukin-11 administration. It was concluded that MKs in murine BM at least in part consist of immature Lin(-)/CD41(+)/CD45(+)/AChE(-) MKs and more differentiated Lin(-)/CD41(++)/CD45(+)/AChE(+) MKs. Immature Lin(-)/CD41(+)/CD45(+)/AChE(-) MKs are a major MK population compared with AChE(+) MKs in BM and play an important role in rapid PLT recovery in vivo.
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产品类型：
产品号#：
03231
04960
04902
04900
04961
04901
04963
04962
04970
04971
产品名：
MethoCult™M3231
MegaCult™-C胶原蛋白和不含细胞因子的培养基
胶原蛋白溶液
MegaCult™-C培养基无细胞因子
MegaCult™-C胶原蛋白和细胞因子培养基
MegaCult™-C细胞因子培养基
双室载玻片试剂盒
MegaCult™-C cfu染色试剂盒
MegaCult™-C不含细胞因子完整试剂盒
MegaCult™-C细胞因子完整试剂盒
Levay K and Slepak VZ (SEP 2007)
The Journal of clinical investigation 117 9 2672--83
Tescalcin is an essential factor in megakaryocytic differentiation associated with Ets family gene expression.
We show here that the process of megakaryocytic differentiation requires the presence of the recently discovered protein tescalcin. Tescalcin is dramatically upregulated during the differentiation and maturation of primary megakaryocytes or upon PMA-induced differentiation of K562 cells. This upregulation requires sustained signaling through the ERK pathway. Overexpression of tescalcin in K562 cells initiates events of spontaneous megakaryocytic differentiation,such as expression of specific cell surface antigens,inhibition of cell proliferation,and polyploidization. Conversely,knockdown of this protein in primary CD34+ hematopoietic progenitors and cell lines by RNA interference suppresses megakaryocytic differentiation. In cells lacking tescalcin,the expression of Fli-1,Ets-1,and Ets-2 transcription factors,but not GATA-1 or MafB,is blocked. Thus,tescalcin is essential for the coupling of ERK cascade activation with the expression of Ets family genes in megakaryocytic differentiation.
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EasySep™小鼠TIL（CD45）正选试剂盒
研究综述Hematopoietic Stem and Progenitor Cells (HSPCs): Isolation, Culture, and Assays
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