Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines
Rat progenitor cells from the germinal region of the fetal mesencephalon were isolated and expanded in media containing the mitogen epidermal growth factor. These cells remained mitotically active (up to 8 months), were immunoreactive for the progenitor cell marker nestin, and were readily infected...
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Veröffentlicht in: | Experimental neurology 1998-02, Vol.149 (2), p.411-423 |
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description | Rat progenitor cells from the germinal region of the fetal mesencephalon were isolated and expanded in media containing the mitogen epidermal growth factor. These cells remained mitotically active (up to 8 months), were immunoreactive for the progenitor cell marker nestin, and were readily infected with the BAGα retrovirus. When incubated in complete media containing serum in poly-l-lysine-coated plates, these cells spontaneously converted to neurons and glia but rarely expressed the dopamine (DA) neuron phenotype. Nineteen different cytokines were screened for their ability to induce the DA phenotype and only interleukin (IL)-1 was found to induce the expression of the DA neuron marker tyrosine hydroxylase (TH). The addition of IL-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) were found to further increase the number of TH immunoreactive (TH-ir) cells. The addition of mesencephalic membrane fragments and striatal culture-conditioned media along with the cytokine mixture induced the expression of morphologically mature TH-ir cells that were also immunoreactive for dopa-decarboxylase, the DA transporter, and DA itself. The DA neuron cell counts were approximately 20–25% of the overall cell population and 50% of the neurofilament population. Astrocytes and oligodendrocytes were also present. These data suggest that hematopoietic cytokines participate in the development of the DA neuron phenotype. Parallels between the function of hematopoietic cytokines in bone marrow and the central nervous system may exist and be useful in understanding the factors which regulate the differentiation of neurons in the brain. |
doi_str_mv | 10.1006/exnr.1998.6715 |
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These cells remained mitotically active (up to 8 months), were immunoreactive for the progenitor cell marker nestin, and were readily infected with the BAGα retrovirus. When incubated in complete media containing serum in poly-l-lysine-coated plates, these cells spontaneously converted to neurons and glia but rarely expressed the dopamine (DA) neuron phenotype. Nineteen different cytokines were screened for their ability to induce the DA phenotype and only interleukin (IL)-1 was found to induce the expression of the DA neuron marker tyrosine hydroxylase (TH). The addition of IL-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) were found to further increase the number of TH immunoreactive (TH-ir) cells. The addition of mesencephalic membrane fragments and striatal culture-conditioned media along with the cytokine mixture induced the expression of morphologically mature TH-ir cells that were also immunoreactive for dopa-decarboxylase, the DA transporter, and DA itself. The DA neuron cell counts were approximately 20–25% of the overall cell population and 50% of the neurofilament population. Astrocytes and oligodendrocytes were also present. These data suggest that hematopoietic cytokines participate in the development of the DA neuron phenotype. Parallels between the function of hematopoietic cytokines in bone marrow and the central nervous system may exist and be useful in understanding the factors which regulate the differentiation of neurons in the brain.</description><identifier>ISSN: 0014-4886</identifier><identifier>EISSN: 1090-2430</identifier><identifier>DOI: 10.1006/exnr.1998.6715</identifier><identifier>PMID: 9500954</identifier><identifier>CODEN: EXNEAC</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Animals ; Astrocytes - cytology ; Biological and medical sciences ; Biomarkers ; Carrier Proteins - metabolism ; Cell Differentiation - drug effects ; Cell Membrane - physiology ; Cells, Cultured ; Corpus Striatum - physiology ; Culture Media, Conditioned ; cytokines ; Cytokines - pharmacology ; Development. Senescence. Regeneration. Transplantation ; differentiation ; Dopa Decarboxylase - biosynthesis ; Dopamine - metabolism ; dopamine neurons ; Dopamine Plasma Membrane Transport Proteins ; Embryo, Mammalian ; Epidermal Growth Factor - pharmacology ; Erythropoietin - pharmacology ; Fibroblast Growth Factor 2 - pharmacology ; Fundamental and applied biological sciences. Psychology ; Glial Cell Line-Derived Neurotrophic Factor ; Growth Inhibitors - pharmacology ; Interleukin-1 - pharmacology ; Interleukin-11 - pharmacology ; Interleukin-6 ; Leukemia Inhibitory Factor ; Lymphokines - pharmacology ; Membrane Glycoproteins ; Membrane Transport Proteins ; mesencephalon ; Mesencephalon - cytology ; Mesencephalon - embryology ; Nerve Growth Factors ; Nerve Tissue Proteins - pharmacology ; Neurons - cytology ; Neurons - drug effects ; Neurons - physiology ; Oligodendroglia - cytology ; progenitor cells ; Rats ; Stem Cells - cytology ; Stem Cells - drug effects ; Tyrosine 3-Monooxygenase - biosynthesis ; Vertebrates: nervous system and sense organs</subject><ispartof>Experimental neurology, 1998-02, Vol.149 (2), p.411-423</ispartof><rights>1998 Academic Press</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-8f793d67af43cf42a3e81ed72c0e39d8c3ce961b4fb33f7b0bca525822a9ca0d3</citedby><cites>FETCH-LOGICAL-c368t-8f793d67af43cf42a3e81ed72c0e39d8c3ce961b4fb33f7b0bca525822a9ca0d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/exnr.1998.6715$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2193444$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9500954$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ling, Zao Dung</creatorcontrib><creatorcontrib>Potter, Elizabeth D.</creatorcontrib><creatorcontrib>Lipton, Jack W.</creatorcontrib><creatorcontrib>Carvey, Paul M.</creatorcontrib><title>Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines</title><title>Experimental neurology</title><addtitle>Exp Neurol</addtitle><description>Rat progenitor cells from the germinal region of the fetal mesencephalon were isolated and expanded in media containing the mitogen epidermal growth factor. These cells remained mitotically active (up to 8 months), were immunoreactive for the progenitor cell marker nestin, and were readily infected with the BAGα retrovirus. When incubated in complete media containing serum in poly-l-lysine-coated plates, these cells spontaneously converted to neurons and glia but rarely expressed the dopamine (DA) neuron phenotype. Nineteen different cytokines were screened for their ability to induce the DA phenotype and only interleukin (IL)-1 was found to induce the expression of the DA neuron marker tyrosine hydroxylase (TH). The addition of IL-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) were found to further increase the number of TH immunoreactive (TH-ir) cells. The addition of mesencephalic membrane fragments and striatal culture-conditioned media along with the cytokine mixture induced the expression of morphologically mature TH-ir cells that were also immunoreactive for dopa-decarboxylase, the DA transporter, and DA itself. The DA neuron cell counts were approximately 20–25% of the overall cell population and 50% of the neurofilament population. Astrocytes and oligodendrocytes were also present. These data suggest that hematopoietic cytokines participate in the development of the DA neuron phenotype. Parallels between the function of hematopoietic cytokines in bone marrow and the central nervous system may exist and be useful in understanding the factors which regulate the differentiation of neurons in the brain.</description><subject>Animals</subject><subject>Astrocytes - cytology</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Membrane - physiology</subject><subject>Cells, Cultured</subject><subject>Corpus Striatum - physiology</subject><subject>Culture Media, Conditioned</subject><subject>cytokines</subject><subject>Cytokines - pharmacology</subject><subject>Development. Senescence. Regeneration. Transplantation</subject><subject>differentiation</subject><subject>Dopa Decarboxylase - biosynthesis</subject><subject>Dopamine - metabolism</subject><subject>dopamine neurons</subject><subject>Dopamine Plasma Membrane Transport Proteins</subject><subject>Embryo, Mammalian</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>Erythropoietin - pharmacology</subject><subject>Fibroblast Growth Factor 2 - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glial Cell Line-Derived Neurotrophic Factor</subject><subject>Growth Inhibitors - pharmacology</subject><subject>Interleukin-1 - pharmacology</subject><subject>Interleukin-11 - pharmacology</subject><subject>Interleukin-6</subject><subject>Leukemia Inhibitory Factor</subject><subject>Lymphokines - pharmacology</subject><subject>Membrane Glycoproteins</subject><subject>Membrane Transport Proteins</subject><subject>mesencephalon</subject><subject>Mesencephalon - cytology</subject><subject>Mesencephalon - embryology</subject><subject>Nerve Growth Factors</subject><subject>Nerve Tissue Proteins - pharmacology</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Oligodendroglia - cytology</subject><subject>progenitor cells</subject><subject>Rats</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - drug effects</subject><subject>Tyrosine 3-Monooxygenase - biosynthesis</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kDtPwzAQgC0EglJY2ZAyILYUv5LYIypPidcAEpvlOOdiSO1ip4j-exK16sZ0p7vvHvoQOiF4QjAuL-DXxwmRUkzKihQ7aESwxDnlDO-iEcaE51yI8gAdpvSJMZacVvtoXxZ9WvARer9y1kIE3zndueCzYLNHSOANLD5060z2EsMMvOtCzKbQtilzvgvZVVjoufMQZz3yBMsYfMrqVTZddeGrr6cjtGd1m-B4E8fo7eb6dXqXPzzf3k8vH3LDStHlwlaSNWWlLWfGcqoZCAJNRQ0GJhthmAFZkprbmjFb1bg2uqCFoFRLo3HDxuh8vXcRw_cSUqfmLpn-Ue0hLJOqZEUL0h8Zo8kaNDGkFMGqRXRzHVeKYDWoVINKNahUg8p-4HSzeVnPodniG3d9_2zT18no1kbtjUtbjBLJOB8wscagt_DjIKpk3OC3cRFMp5rg_vvgD23ZkW0</recordid><startdate>19980201</startdate><enddate>19980201</enddate><creator>Ling, Zao Dung</creator><creator>Potter, Elizabeth D.</creator><creator>Lipton, Jack W.</creator><creator>Carvey, Paul M.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19980201</creationdate><title>Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines</title><author>Ling, Zao Dung ; Potter, Elizabeth D. ; Lipton, Jack W. ; Carvey, Paul M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-8f793d67af43cf42a3e81ed72c0e39d8c3ce961b4fb33f7b0bca525822a9ca0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Astrocytes - cytology</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Membrane - physiology</topic><topic>Cells, Cultured</topic><topic>Corpus Striatum - physiology</topic><topic>Culture Media, Conditioned</topic><topic>cytokines</topic><topic>Cytokines - pharmacology</topic><topic>Development. Senescence. Regeneration. Transplantation</topic><topic>differentiation</topic><topic>Dopa Decarboxylase - biosynthesis</topic><topic>Dopamine - metabolism</topic><topic>dopamine neurons</topic><topic>Dopamine Plasma Membrane Transport Proteins</topic><topic>Embryo, Mammalian</topic><topic>Epidermal Growth Factor - pharmacology</topic><topic>Erythropoietin - pharmacology</topic><topic>Fibroblast Growth Factor 2 - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glial Cell Line-Derived Neurotrophic Factor</topic><topic>Growth Inhibitors - pharmacology</topic><topic>Interleukin-1 - pharmacology</topic><topic>Interleukin-11 - pharmacology</topic><topic>Interleukin-6</topic><topic>Leukemia Inhibitory Factor</topic><topic>Lymphokines - pharmacology</topic><topic>Membrane Glycoproteins</topic><topic>Membrane Transport Proteins</topic><topic>mesencephalon</topic><topic>Mesencephalon - cytology</topic><topic>Mesencephalon - embryology</topic><topic>Nerve Growth Factors</topic><topic>Nerve Tissue Proteins - pharmacology</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Oligodendroglia - cytology</topic><topic>progenitor cells</topic><topic>Rats</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - drug effects</topic><topic>Tyrosine 3-Monooxygenase - biosynthesis</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ling, Zao Dung</creatorcontrib><creatorcontrib>Potter, Elizabeth D.</creatorcontrib><creatorcontrib>Lipton, Jack W.</creatorcontrib><creatorcontrib>Carvey, Paul M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ling, Zao Dung</au><au>Potter, Elizabeth D.</au><au>Lipton, Jack W.</au><au>Carvey, Paul M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>1998-02-01</date><risdate>1998</risdate><volume>149</volume><issue>2</issue><spage>411</spage><epage>423</epage><pages>411-423</pages><issn>0014-4886</issn><eissn>1090-2430</eissn><coden>EXNEAC</coden><abstract>Rat progenitor cells from the germinal region of the fetal mesencephalon were isolated and expanded in media containing the mitogen epidermal growth factor. These cells remained mitotically active (up to 8 months), were immunoreactive for the progenitor cell marker nestin, and were readily infected with the BAGα retrovirus. When incubated in complete media containing serum in poly-l-lysine-coated plates, these cells spontaneously converted to neurons and glia but rarely expressed the dopamine (DA) neuron phenotype. Nineteen different cytokines were screened for their ability to induce the DA phenotype and only interleukin (IL)-1 was found to induce the expression of the DA neuron marker tyrosine hydroxylase (TH). The addition of IL-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) were found to further increase the number of TH immunoreactive (TH-ir) cells. The addition of mesencephalic membrane fragments and striatal culture-conditioned media along with the cytokine mixture induced the expression of morphologically mature TH-ir cells that were also immunoreactive for dopa-decarboxylase, the DA transporter, and DA itself. The DA neuron cell counts were approximately 20–25% of the overall cell population and 50% of the neurofilament population. Astrocytes and oligodendrocytes were also present. These data suggest that hematopoietic cytokines participate in the development of the DA neuron phenotype. Parallels between the function of hematopoietic cytokines in bone marrow and the central nervous system may exist and be useful in understanding the factors which regulate the differentiation of neurons in the brain.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>9500954</pmid><doi>10.1006/exnr.1998.6715</doi><tpages>13</tpages></addata></record> |
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subjects | Animals Astrocytes - cytology Biological and medical sciences Biomarkers Carrier Proteins - metabolism Cell Differentiation - drug effects Cell Membrane - physiology Cells, Cultured Corpus Striatum - physiology Culture Media, Conditioned cytokines Cytokines - pharmacology Development. Senescence. Regeneration. Transplantation differentiation Dopa Decarboxylase - biosynthesis Dopamine - metabolism dopamine neurons Dopamine Plasma Membrane Transport Proteins Embryo, Mammalian Epidermal Growth Factor - pharmacology Erythropoietin - pharmacology Fibroblast Growth Factor 2 - pharmacology Fundamental and applied biological sciences. Psychology Glial Cell Line-Derived Neurotrophic Factor Growth Inhibitors - pharmacology Interleukin-1 - pharmacology Interleukin-11 - pharmacology Interleukin-6 Leukemia Inhibitory Factor Lymphokines - pharmacology Membrane Glycoproteins Membrane Transport Proteins mesencephalon Mesencephalon - cytology Mesencephalon - embryology Nerve Growth Factors Nerve Tissue Proteins - pharmacology Neurons - cytology Neurons - drug effects Neurons - physiology Oligodendroglia - cytology progenitor cells Rats Stem Cells - cytology Stem Cells - drug effects Tyrosine 3-Monooxygenase - biosynthesis Vertebrates: nervous system and sense organs |
title | Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines |
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