Mapping human pluripotent stem cell differentiation. Kegg pathway analysis were performed as pathway annotation d. Understanding the basic knowledge of hscs is useful for stem cell biology research and. The weakening immune response has been attributed to a shift from a balanced lymphoidmyeloid output toward a myeloid skew with age rossi et al. May 20, 2019 rspondin2 promotes generation of hematopoietic progenitors from hescs. Jul 27, 2018 human pluripotent stem cell hpscderived hematopoietic stem and progenitor cells hspcs may be used to model human hematopoietic differentiation, to produce large quantities of blood lineage cells for therapeutic purposes and to model human hematological diseases 1, 2. Hladrb1, hladrb5, and cx3cr1 were related to hematopoietic cell lineage, intestinal immune network for iga production, natural killer cell mediated cytotoxicity, nod like receptor signaling pathway, t cell receptor signaling pathway, and toll like. Hcls1 hematopoietic lineage cellspecific protein homo.
A total of 1178 demrnas and 273 delncrnas between luminalb breast cancer tumor tissues and adjacent tissues were obtained. View or download all content the institution has subscribed to. Proliferation drives agingrelated functional decline in a subpopulation of the hematopoietic stem cell compartment. Gonadotropinreleasing hormone signaling pathway induces the synthesis and secretion of luteinizing and folliclestimulating hormones from the pituitary. Nov 18, 2019 in kegg pathway analysis, the complement and coagulation cascade pathway are involved in early infection. Based on kegg pathway analysis, the degs were significantly enriched in pathways associated with cytokinecytokine receptor interaction, the chemokine signaling pathway, cell adhesion molecules, staphylococcus aureus infection, and the hematopoietic cell lineage.
Cell cycle rno04110, ecmreceptor interaction rno04512, complement and coagulation cascades rno04610, focal adhesion rno04510, hematopoietic cell lineage rno04640, and neuroactive ligandreceptor interactions rno04080 are potential therapeutic targets of thswd in mcao. Click on a cell type below to view a subset of molecules used as markers for the identification of that cell type. Hematopoietic stem cells hscs play a key role in hematopoietic system that functions mainly in homeostasis and immune response. A series of molecular signals generated as a consequence of activation of the transmembrane protein smoothened. We use high throughput singlecell rnasequencing scrnaseq, based on optimized microfluidic circuits, to profile early. Margaret goodell, wei li and colleagues report conditional ablation of the dnmt3a dna methyltransferase in hematopoietic stem cells hscs in mice. The natural history of cml has a triphasic clinical course comprising of an initial chronic phase cp, which is characterized by expansion of functionally normal myeloid cells, followed by an accelerated phase ap and finally a more aggressive blast phase bp, with loss of terminal. Zon1,3 1stem cell program and division of hematologyoncology childrens hospital and dana farber cancer institute, howard. The mean expression value for each kegg pathway was obtained by taking the mean of the expression values of each gene on the microarray for a given kegg pathway. Genetic background of immune complications after allogeneic. The quiescence and potency of hematopoietic stem cells hscs are thought to be maintained by glycolysis. Substance record sid 17396767 for tocilizumab usaninn submitted by kegg. Distinct signaling programs control human hematopoietic stem. In that way, the reporting rate of a certain adverse.
Restraining lysosomal activity preserves hematopoietic. For the kegg pathway enrichment analysis, as shown in figure 3d, epsteinbarr virus infection was the most significant enriched pathway, followed by hematopoietic cell lineage. Hematopoietic stem and progenitor cells can be cultured under defined conditions designed either to promote selfrenewal and increase the number of primitive cells, or to promote lineage specific expansion and differentiation into mature blood cell types. Using oligonucleotide microarrays, we compared gene expression patterns of multiple purified hematopoietic cell populations, including neutrophils, monocytes, macrophages, resting, centrocytic, and centroblastic b lymphocytes, dendritic cells, and hematopoietic stem. Each pathway map is identified by the combination of 24 letter prefix code and 5 digit number see kegg identifier. A cmp gives rise to the myeloid lineage, which comprises the rest of the leukocytes, the erythrocytes red blood cells, and the megakaryocytes that produce platelets important in blood clotting. However, hscs persist in the small quantity within the body, mostly in the quiescent state. Kegg pathway is the reference database for pathway mapping in kegg mapper. Additionally, we identified the immunerelated degs and found that biological processes of these degs mainly involved immune response, inflammatory response, and cellcell signaling, and kegg pathways were concentrated on cytokinecytokine receptor interaction and hematopoietic cell lineage.
The hscs that maintain homeostasis of the adult hematopoietic system are generated during embryogenesis, but are not the first blood cells to be formed in the embryo. Hematopoietic stem cell fate is established by the notchrunx pathway caroline erter burns, 1david traver,2 elizabeth mayhall, jennifer l. Jackie damen is the scientific director of the contract assay services department. The b cell receptor bcr is an integral membrane protein complex that is composed of two immunoglobulin ig heavy chains, two ig light chains and two heterodimers of igalpha and igbeta.
Screening and identification of key candidate genes and. Hsc expansion strategies, including recent reports of significant improvements using small molecule supplemented cultures, generally rely on the concomitant effects of gfs to promote hsc survival and mitogenesis. Mapping differentiation pathways from hematopoietic stem. Due to the rare and transient nature, the hsccompetent hecs. Clinical research paper carboplatininduced hematotoxicity. This cytokine plays an important role in hematopoiesis formation of blood cells, spermatogenesis, and melanogenesis. They produce and secrete millions of different antibody molecules, each of which recognizes a different foreign antigen. Transcriptomic analysis of nibea albiflora skin in response. Both types of cell products are being explored for their utility as cell therapeutics and. The stem cell lineage database scld is a database of resources used to identify cell lineages the stem cell lineage database scld was created by the university of connecticut in order to have a more user friendly approach to retrieve and share data. Integrative network analysis of signaling in human cd34.
The mean expression value of all kegg pathways for each hematopoietic cell type was obtained using all the genes on the array not limited to the fingerprints. Hscs transplantation has been applied for the treatment of several diseases. This indicated that carboplatin could profoundly affect the development of blood cells. Hematopoietic cell lineage, cytokinecytokine receptor interaction, cell adhesion molecules cams and primary immunodeficiency were significantly enriched kegg pathways in luminalb breast cancer. Predicting pathway membership via domain signatures. Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. Hsc emergence is preceded by primitive and definitive waves that are defined by limited differentiation potentials. Through those studies, human hematopoietic cell fate has been shown to be tightly regulated by the differential activity of different signaling pathways. By exploiting mitochondrial heterogeneity, liang, arif, et al. Hematopoietic cell lineage, natural killer nk cellmediated cytotoxicity, and the intestinal immune network for iga production are involved in later infection.
Categorize these 87 genes by gene family show members show 87 members mapped to 87 genes. Covid19 is an emerging, rapidly evolving situation. Hematopoietic stem cells play important roles for angiogenesis. Mar 28, 2019 upregulated genes in gene ontology were significantly enriched in immune responses, and those in the kyoto encyclopedia of genes and genomes pathway were significantly enriched in the cytokinecytokine receptor interaction pathway, cell adhesion molecules, and hematopoietic cell lineage. Upregulated genes in gene ontology were significantly enriched in immune responses, and those in the kyoto encyclopedia of genes and genomes pathway were significantly enriched in the cytokinecytokine receptor interaction pathway, cell adhesion molecules, and hematopoietic cell lineage. Go and kegg pathway analyses to explore the potential functions of lncrnas in hbf induction, we performed go analysis on aberrantly expressed mrnas. Hematopoietic stem cells hscs are a specialized group of cells with the ability to selfrenew and differentiate into distinct lineages of the entire hematopoietic system throughout lifetime.
Several methods of hspc differentiation have been developed. Distinct signaling programs control human hematopoietic stem cell survival and proliferation. Hematopoietic stem cell transplantation and blood cell transfusion such as the use of red blood cells and platelet have been widely applied as potent treatments of multiple blood. Restraining lysosomal activity preserves hematopoietic stem. Using oligonucleotide microarrays, we compared gene expression patterns of multiple purified hematopoietic cell populations, including neutrophils, monocytes, macrophages, resting, centrocytic, and centroblastic b lymphocytes, dendritic cells, and hematopoietic. It is worth mentioning that the hematopoietic cell lineage pathway also changes, which may make it easy to transfer the characteristics of the source. Given the early awareness of the hematologic risks, great caution should be exercised in prescribing carboplatin to nonsmall cell lung cancer patients. The hematopoietic system offers many advantages as a model for understanding general aspects of lineage choice and specification. Conditional knockin of dnmt3a r878h initiates acute. Recently, the immunological genome project immgen completed the first phase of the goal to understand the molecular circuitry underlying the immune cell lineage in mice. Sep 01, 2012 the hematopoietic system can be considered a model paradigm for dissecting stem cell differentiation pathways, as it has been established that a single, multipotent hematopoietic stem cell hsc can both selfrenew and give rise to all mature blood cell types. Microarray technique allows for simultaneous assessment of expression of nearly all human genes.
However, a comprehensive singlecell level differentiation roadmap for hpscs has not been achieved. Mar 20, 2020 hematopoietic stem cells hscs in adults are believed to be born from hemogenic endothelial cells hecs in midgestational embryos. Rspondin2 promotes hematopoietic differentiation of human. Hematopoietic stem cell development, niches, and signaling. The downregulation of genes within the pathway hematopoietic cell lineage may be related to the specific antiangiogenic action of bevacizumab 33, 34. Cell signaling pathways involved in hematopoietic stem. Apr 27, 2004 the hematopoietic system offers many advantages as a model for understanding general aspects of lineage choice and specification. Substance record sid 172232447 for dupilumab usan submitted by kegg. Kegg pathway analysis revealed that enrichment of degs was mostly in primary immunodeficiency, hematopoietic cell lineage, foxo signaling pathway, hippo signaling pathway, transcriptional misregulation in cancer. A total of 33 children referred for hsct were enrolled in. Kegg pathway number of human genes in the category number of carboplatinrelated genes in the. The ecmreceptor interaction and hematopoietic cell lineage were altered in the kidney additional file 2, kegg terms.
Damen has acquired extensive experience in the field of hematopoiesis, where her key strengths lie in stem cell biology, protein biochemistry and signalling, especially in the area of erythropoietin. Scf can exist both as a transmembrane protein and a soluble protein. Identification of key pathways and genes in tp53 mutation. Embryonic endothelial evolution towards first hematopoietic. Search for kegg pathways containing human genes with a mnemiopsis homolog by selecting a kegg identifier, a kegg pathway, or a gene symbol of interest from one of the lists below. Enriched by target genes of the plant pathway category top level pathway category second level kegg pathway name no. Lineage specificity of gene expression patterns pnas.
Substrate of the antigen receptorcoupled tyrosine kinase. Role of classical signaling pathways in stem cell maintenance a cardoso and n carlesso, section editors published. Stem cell factor also known as scf, kitligand, kl, or steel factor is a cytokine that binds to the ckit receptor. To discover novel regulators of hpsc early hematopoietic differentiation, we recently conducted rnaseq screening and identified the role of meis1 and meis2 in modulating formation of hep from mesoderm cells and in eht, respectively 26, 27. Frontiers screening the cancer genome atlas database for. Identification of differentially expressed lncrnas and. Blood cell development progresses from a hematopoietic stem cell hsc, which can undergo either selfrenewal or differentiation into a multilineage committed progenitor cell. Precise activation and inactivation of cdks at specific points in the cell cycle are required for orderly cell division. Translocation products in acute myeloid leukemia activate the wnt signaling pathway in hematopoietic cells. Finally, starch and sucrose metabolism, chemokine signaling, and cytokinecytokine receptor interaction were influenced in. Gtex compendium human tissue compendium novartis global cancer map broad institute nci60 cell lines national cancer institute advanced query. We applied our method to predict the kegg pathway membership for a microarray dataset produced in our department. Cyclincdk inhibitors ckis, such as p16ink4a, p15ink4b, p27kip1, and p21cip1, are involved in the negative regulation of cdk activities, thus providing a pathway through which the cell cycle is negatively regulated. Investigation of molecular biomarker candidates for diagnosis.
Expression and significance of molecular profiles on. All cellular blood components are derived from haematopoietic stem cells. The final outcome of these changed signaling pathways changed the apoptosis pathway and the hematopoietic cell lineage pathway, so that the liver cells showed a unique pathology. Human pluripotent stem cells hpscs provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. Profiles of immune cell infiltration in head and neck. Leucinerich repeatcontaining gproteincoupled receptor. The notchjagged pathway inhibits proliferation of human. Chronic myeloid leukemia cml is a clonal myeloproliferative disorder of a pluripotent stem cell. A cmp gives rise to the myeloid lineage, which comprises the rest of the leukocytes, the erythrocytes red blood cells, and the megakaryocytes that produce platelets important in. Jan 19, 2017 growth factors gfs represent a cornerstone of most hematopoietic stem cell hsc manipulations for experimental and clinical purposes. Immune reactions are among the most serious complications observed after hematopoietic stem cell transplantation hsct in children. Src3 is involved in maintaining hematopoietic stem cell.
Hematopoietic cell lineage, natural killer nk cell mediated cytotoxicity, and the intestinal immune network for iga production are involved in later infection. Quiescence is maintained by an abundance of lysosomes whose repression enhances hsc potency by over 90fold. Cell signaling pathways involved in hematopoietic stem cell. Hematopoietic stem cell development, niches, and signaling pathways.
Hcls1 hematopoietic lineage cellspecific protein mus. May also be involved in the regulation of gene expression by similarity. Investigation of molecular biomarker candidates for. Human pluripotent stem cell hpscderived hematopoietic stem and progenitor cells hspcs may be used to model human hematopoietic differentiation, to produce large quantities of blood lineage cells for therapeutic purposes and to model human hematological diseases 1, 2. Differential protein network analysis of the immune cell. A clp gives rise to the lymphoid lineage of white blood cells or leukocytesthe natural killer nk cells and the t and b lymphocytes. However, unbiased global phosphoproteomic analysis of hspc has not yet been reported and relatively little is known about pathway substrates critical to cell fate decisions. Dec 10, 2014 hematopoietic stem cell emergence in the vertebrate embryo. In the hematopoietic system, stem cell aging is evident in a weakening of the adaptive immune response and a general decline of hematopoietic stem cell fitness beerman et al. That milestone resulted in the creation of the most comprehensive collection of gene expression profiles in the immune cell lineage in any model organism of human disease. Disease 1 kegg disease 1 chemical substance 1 kegg compound 1 gene 56110 kegg orthology 57 refgene 56053. A total of 33 children referred for hsct were enrolled in the. In kegg pathway analysis, upregulated degs were significantly enriched in extracellular matrix ecmreceptor interaction, rap1 signaling pathway, pi3kakt signaling pathway, hematopoietic cell lineage, calcium signaling pathway, cell adhesion. Distinct signaling programs control human hematopoietic.
Biphasic modulation of insulin signaling enables highly. The mean expression value of all kegg pathways for each hematopoietic cell type was obtained using all. Transcriptomic analysis of nibea albiflora skin in. In kegg pathway analysis, the complement and coagulation cascade pathway are involved in early infection. The objective of the study was to compare the whole genome expression in children before and after hsct. Proliferation drives agingrelated functional decline in a. Hematopoietic stem cells hscs in adults are believed to be born from hemogenic endothelial cells hecs in midgestational embryos. Genomewide analysis of aberrantly expressed lncrnas and.
737 812 1414 723 495 1465 1292 83 669 64 1243 619 1612 1382 371 1224 181 909 849 454 409 1613 673 210 750 296 1321 1163 1499 21 728 1493 836 1275 303 121 493 941 1240