共查询到20条相似文献，搜索用时 45 毫秒
1.
MicroRNAs modulate hematopoietic lineage differentiation 总被引：8，自引：0，他引：8
2.
The immune system develops in waves during ontogeny; it is initially populated by cells generated from fetal hematopoietic stem cells (HSCs) and later by cells derived from adult HSCs. Remarkably, the genetic programs that control these two distinct stem cell fates remain poorly understood. We report that Lin28b is specifically expressed in mouse and human fetal liver and thymus, but not in adult bone marrow or thymus. We demonstrate that ectopic expression of Lin28 reprograms hematopoietic stem/progenitor cells (HSPCs) from adult bone marrow, which endows them with the ability to mediate multilineage reconstitution that resembles fetal lymphopoiesis, including increased development of B-1a, marginal zone B, gamma/delta (γδ) T cells, and natural killer T (NKT) cells. 相似文献
3.
Cheng T Rodrigues N Shen H Yang Y Dombkowski D Sykes M Scadden DT 《Science (New York, N.Y.)》2000,287(5459):1804-1808
Relative quiescence is a defining characteristic of hematopoietic stem cells, while their progeny have dramatic proliferative ability and inexorably move toward terminal differentiation. The quiescence of stem cells has been conjectured to be of critical biologic importance in protecting the stem cell compartment, which we directly assessed using mice engineered to be deficient in the G1 checkpoint regulator, cyclin-dependent kinase inhibitor, p21cip1/waf1 (p21). In the absence of p21, hematopoietic stem cell proliferation and absolute number were increased under normal homeostatic conditions. Exposing the animals to cell cycle-specific myelotoxic injury resulted in premature death due to hematopoietic cell depletion. Further, self-renewal of primitive cells was impaired in serially transplanted bone marrow from p21-/- mice, leading to hematopoietic failure. Therefore, p21 is the molecular switch governing the entry of stem cells into the cell cycle, and in its absence, increased cell cycling leads to stem cell exhaustion. Under conditions of stress, restricted cell cycling is crucial to prevent premature stem cell depletion and hematopoietic death. 相似文献
4.
A retroviral expression vector (N2) containing the selectable gene, neoR, has been used to determine the optimal conditions for infecting murine hematopoietic progenitor cells at high efficiency. After infected bone marrow cells were introduced into lethally irradiated mice, the presence, stability, and expression of the vector DNA sequences were analyzed either in individual spleen foci 10 days later or in the blood, bone marrow, and spleens of mice 4 months later. When bone marrow cells were cultured in medium containing virus with titers of more than 10(6) colony-forming units per milliliter in the presence of purified murine interleukin-3, more than 85 percent of the resulting foci contained vector DNA. This proviral vector DNA was intact. Efficient expression of the neoR gene was demonstrated in most of the DNA-positive foci examined. The spleens of reconstituted animals (over a long term) contained intact "vector DNA" and the blood and bone marrow expressed the neoR gene in some animals. Thus, a retroviral vector can be used to introduce intact exogenous DNA sequences into hematopoietic stem cells with high efficiency and with substantial expression. 相似文献
5.
6.
A stem cell molecular signature 总被引：2，自引：0，他引：2
Ivanova NB Dimos JT Schaniel C Hackney JA Moore KA Lemischka IR 《Science (New York, N.Y.)》2002,298(5593):601-604
Mechanisms regulating self-renewal and cell fate decisions in mammalian stem cells are poorly understood. We determined global gene expression profiles for mouse and human hematopoietic stem cells and other stages of the hematopoietic hierarchy. Murine and human hematopoietic stem cells share a number of expressed gene products, which define key conserved regulatory pathways in this developmental system. Moreover, in the mouse, a portion of the genetic program of hematopoietic stem cells is shared with embryonic and neural stem cells. This overlapping set of gene products represents a molecular signature of stem cells. 相似文献
7.
Regulation of expression of the interleukin-2 receptor on hematopoietic cells by interleukin-3 总被引：4，自引：0，他引：4
M C Birchenall-Sparks W L Farrar D Rennick P L Kilian F W Ruscetti 《Science (New York, N.Y.)》1986,233(4762):455-458
Remarkable similarities in the intracellular and genetic events occur when lymphoid and hematopoietic cells are exposed to their specific growth factors. The interleukin-2 (IL-2) receptor, whose cell-surface expression is an absolute requirement for the growth and differentiation of lymphoid cells, was detected on various nonlymphoid hematopoietic cell types in this study. Cell lines consisting either of granulocyte-macrophage precursors or mast cells, which are dependent on interleukin-3 (IL-3) for their growth, expressed high levels of the IL-2 receptor on their surface. Analysis of the binding characteristics of these receptors with 125I-labeled recombinant IL-2 revealed that only receptors with low affinity for IL-2 were present on these cells. Addition of purified recombinant IL-3 to these cell lines led to an increase in IL-2 receptor gene expression within 1 hour in isolated nuclei. This IL-3--induced increase in the number of IL-2 receptors on the cell surface is maximal within 24 hours. Addition of 10,000 units of IL-2 to these cells had no apparent effect on their growth or differentiation. The presence of the receptor with only low affinity for IL-2 on hematopoietic cells and the regulation by IL-3 suggest that this receptor is involved in some important metabolic event in hematopoiesis. 相似文献
8.
To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes in these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, in GFP+:GFP- parabiotic mice, we found substantial chimerism of hematopoietic but not nonhematopoietic cells. These data indicate that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all. 相似文献
9.
Studies of the human c-myb gene and its product in human acute leukemias 总被引：23，自引：0，他引：23
D J Slamon T C Boone D C Murdock D E Keith M F Press R A Larson L M Souza 《Science (New York, N.Y.)》1986,233(4761):347-351
The myb gene is the transforming oncogene of the avian myeloblastosis virus (AMV); its normal cellular homolog, c-myb, is conserved across a broad span of evolution. In humans, c-myb is expressed in malignant hematopoietic cell lines and in primary hematopoietic tumors. Partial complementary DNA clones were generated from blast cells of patients with acute myelogenous leukemia. The sequences of the clones were compared to the c-myb of other species, as well as the v-myb of AMV. In addition, the carboxyl terminal region of human c-myb was placed in an expression vector to obtain protein for the generation of antiserum, which was used to identify the human c-myb gene product. Like v-myb, this protein was found within the nucleus of leukemic cells where it was associated with the nuclear matrix. These studies provide further evidence that c-myb might be involved in human leukemia. 相似文献
10.
胚胎干细胞体外定向诱导分化研究进展 总被引：3，自引：1，他引：3
胚胎干细胞是由早期内细胞团分离的一种多潜能细胞 ,在体外分化抑制培养时 ,可保持未分化状态而无限增殖。一旦撤除分化抑制因素 ,或添加适当的诱导剂 ,ES细胞可分化为内胚层、中胚层和外胚层的多种类型的特化细胞。文章综述了体外定向诱导 ES细胞分化为造血细胞、心肌细胞、神经细胞、脂肪细胞、胰岛细胞、内皮细胞、上皮细胞、成骨细胞、软骨细胞和黑素细胞等的途径和方法。 相似文献
11.
Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment 总被引：1，自引：0，他引：1
Notta F Doulatov S Laurenti E Poeppl A Jurisica I Dick JE 《Science (New York, N.Y.)》2011,333(6039):218-221
Lifelong blood cell production is dependent on rare hematopoietic stem cells (HSCs) to perpetually replenish mature cells via a series of lineage-restricted intermediates. Investigating the molecular state of HSCs is contingent on the ability to purify HSCs away from transiently engrafting cells. We demonstrated that human HSCs remain infrequent, using current purification strategies based on Thy1 (CD90) expression. By tracking the expression of several adhesion molecules in HSC-enriched subsets, we revealed CD49f as a specific HSC marker. Single CD49f(+) cells were highly efficient in generating long-term multilineage grafts, and the loss of CD49f expression identified transiently engrafting multipotent progenitors (MPPs). The demarcation of human HSCs and MPPs will enable the investigation of the molecular determinants of HSCs, with a goal of developing stem cell-based therapeutics. 相似文献
12.
Phillips RL Ernst RE Brunk B Ivanova N Mahan MA Deanehan JK Moore KA Overton GC Lemischka IR 《Science (New York, N.Y.)》2000,288(5471):1635-1640
Blood cell production originates from a rare population of multipotent, self-renewing stem cells. A genome-wide gene expression analysis was performed in order to define regulatory pathways in stem cells as well as their global genetic program. Subtracted complementary DNA libraries from highly purified murine fetal liver stem cells were analyzed with bioinformatic and array hybridization strategies. A large percentage of the several thousand gene products that have been characterized correspond to previously undescribed molecules with properties suggestive of regulatory functions. The complete data, available in a biological process-oriented database, represent the molecular phenotype of the hematopoietic stem cell. 相似文献
13.
Gu Y Filippi MD Cancelas JA Siefring JE Williams EP Jasti AC Harris CE Lee AW Prabhakar R Atkinson SJ Kwiatkowski DJ Williams DA 《Science (New York, N.Y.)》2003,302(5644):445-449
The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function. 相似文献
14.
Our understanding of leukemia development and progression has been hampered by the lack of in vivo models in which disease is initiated from primary human hematopoietic cells. We showed that upon transplantation into immunodeficient mice, primitive human hematopoietic cells expressing a mixed-lineage leukemia (MLL) fusion gene generated myeloid or lymphoid acute leukemias, with features that recapitulated human diseases. Analysis of serially transplanted mice revealed that the disease is sustained by leukemia-initiating cells (L-ICs) that have evolved over time from a primitive cell type with a germline immunoglobulin heavy chain (IgH) gene configuration to a cell type containing rearranged IgH genes. The L-ICs retained both myeloid and lymphoid lineage potential and remained responsive to microenvironmental cues. The properties of these cells provide a biological basis for several clinical hallmarks of MLL leukemias. 相似文献
15.
为研究胚胎不同时期VEGF、KDR和CD34在人卵黄囊中的表达情况,了解胚胎造血的发育过程和机理。采用免疫组织化学SP法卵黄囊冰冻切片进行染色,光镜观察。结果发现在第3￣4周的人卵黄囊低表达VEGF和KDR,不表达CD34。4￣6周组强表达VEGF、KDR和CD34。在血岛内阳性细胞大而圆,成簇或分散聚集,有些细胞沿血岛边缘形成血管样结构。6周以后,卵黄囊弱表达VEGF、KDR和CD34。上述结果提示卵黄囊可表达造血和血管生成相关因子,随胚胎发育呈阶段性表达。卵黄囊中出现造血干细胞和血管内皮细胞的分化。 相似文献
16.
Christopherson KW Hangoc G Mantel CR Broxmeyer HE 《Science (New York, N.Y.)》2004,305(5686):1000-1003
Hematopoietic stem cell homing and engraftment are crucial to transplantation efficiency, and clinical engraftment is severely compromised when donor-cell numbers are limiting. The peptidase CD26 (DPPIV/dipeptidylpeptidase IV) removes dipeptides from the amino terminus of proteins. We present evidence that endogenous CD26 expression on donor cells negatively regulates homing and engraftment. By inhibition or deletion of CD26, it was possible to increase greatly the efficiency of transplantation. These results suggest that hematopoietic stem cell engraftment is not absolute, as previously suggested, and indicate that improvement of bone marrow transplant efficiency may be possible in the clinic. 相似文献
17.
【目的】探究抗氧化剂-水溶性维生素E的类似物（Trolox）通过调控活性氧对猪肌肉干细胞增殖及分化过程产生的影响,为进一步优化培养肉种子细胞在体外增殖及分化过程提供研究基础。【方法】首先在猪肌肉干细胞增殖过程中,添加不同浓度（0、50、100和200 μmol∙L-1）的Trolox培养3 d,利用血细胞计数板进行细胞计数,统计细胞增殖倍数,同时利用CCK8技术检测不同浓度的Trolox对细胞增殖的影响;利用RT-qPCR技术检测不同浓度Trolox处理后表征干性的PAX7表达水平,Western Blotting技术检测PAX7蛋白的表达水平;通过CellROX荧光染料对细胞内活性氧进行染色并通过高通量高内涵活细胞共聚焦成像系统检测Trolox对活性氧的调控作用;进一步在猪肌肉干细胞体外成肌分化进程中添加Trolox处理,利用RT-qPCR技术检测分化早期标志基因MYOG、CAV-3及终末分化标志基因肌球蛋白重链（MyHC）的表达水平,并利用Western Blotting技术检测MyHC蛋白的表达,利用免疫荧光技术对MyHC进行染色并统计MyHC阳性细胞比例。【结果】细胞增殖倍数统计显示,50和100 μmol∙L-1的Trolox处理组猪肌肉干细胞增殖倍数显著高于对照组（P<0.05）;CCK8测得50和100 μmol∙L-1 Trolox处理组第3天的吸光值显著高于对照组（P<0.05）;100和200 μmol∙L-1的Trolox显著上调了PAX7的表达（P<0.05）,对PAX7蛋白的表达有上调趋势,但无显著差异（P>0.05）;添加Trolox后,细胞内活性氧水平被极显著降低（P<0.001）;在分化进程中添加Trolox后,预分化阶段的MYOG和CAV-3及终末分化阶段的MyHC均显著上调（P<0.05）,而Western blotting结果显示MyHC蛋白的表达无显著变化（P>0.05）;免疫荧光结果显示MyHC阳性细胞比例有增多的趋势,但无显著差异（P>0.05）。【结论】Trolox通过降低细胞内的活性氧,促进猪肌肉干细胞的增殖以及分化进程。 相似文献
18.
Transforming growth factor-beta (TGF-beta) and TGF-beta-related proteins, such as the bone morphogenetic proteins, have emerged as key regulators of stem cell renewal and differentiation. These proteins have disparate roles in regulating the biology of embryonic stem cells and tumor suppression, and they help define the selection of cell fate and the progression of differentiation along a lineage. Here we illustrate their roles in embryonic stem cells and in the differentiation of neural, hematopoietic, mesenchymal, and gastrointestinal epithelial stem cells. 相似文献
19.
为了研究固始鸡脐带间充质干细胞（umbilical cord mesenchymal stem cells,UCMSCs）的生物学特性和诱导分化,对其进行原代培养及定向诱导分化研究。选取14日龄固始鸡鸡胚的脐带组织,剥离脐带动、静脉,将华通胶部分剪成1 mm3大小,采用胶原酶消化法分离细胞并进行原代培养,观察细胞形态,绘制P3、P9、P15代生长曲线并测定群体倍增时间及克隆形成能力。结果表明,固始鸡UCMSCs形态为长梭形,生长趋势符合Logistic生长曲线规律,呈典型的S形;免疫荧光和RT-PCR结果显示,固始鸡UCMSCs表达CD29、CD44、CD73、CD90、CD166等间充质干细胞表面标记物基因,但不表达原始造血祖细胞标志物CD34和泛白细胞标志物CD45;经特异性染色和RT-PCR表明,体外诱导固始鸡UCMSCs可分化为脂肪、成骨和成软骨细胞。从固始鸡脐带华通胶中分离所获得的UCMSCs具有良好的体外增殖能力和分化潜能,与从其他物种体内分离的UCMSCs具有相似的生物学特征,它们的多项分化能力预示着细胞移植的应用前景,可为再生医学和组织工程学提供新的潜在种子细胞。 相似文献
20.
Mammalian neural stem cells 总被引：4，自引：0，他引：4
Gage FH 《Science (New York, N.Y.)》2000,287(5457):1433-1438
Neural stem cells exist not only in the developing mammalian nervous system but also in the adult nervous system of all mammalian organisms, including humans. Neural stem cells can also be derived from more primitive embryonic stem cells. The location of the adult stem cells and the brain regions to which their progeny migrate in order to differentiate remain unresolved, although the number of viable locations is limited in the adult. The mechanisms that regulate endogenous stem cells are poorly understood. Potential uses of stem cells in repair include transplantation to repair missing cells and the activation of endogenous cells to provide "self-repair. " Before the full potential of neural stem cells can be realized, we need to learn what controls their proliferation, as well as the various pathways of differentiation available to their daughter cells. 相似文献