Cristina Zalfa, C. Grasselli, G. Santilli, D. Ferrari, G. Lamorte, A. Vescovi, L. Filippis
{"title":"GFAP δ作为人神经胶质祖细胞分化标记","authors":"Cristina Zalfa, C. Grasselli, G. Santilli, D. Ferrari, G. Lamorte, A. Vescovi, L. Filippis","doi":"10.4172/2157-7633.1000437","DOIUrl":null,"url":null,"abstract":"Background: Human Neural Stem Cells (hNSCs) are responsible for brain development at prenatal and postnatal stages and for tissue homeostasis and repair after injury on adulthood. The identification of hNSC specific markers is still a debated argument. GFAP-δ, the delta isoform of Glial Fibrillary Acidic Protein (GFAP), is particularly expressed in the Subventricular Zone (SVZ) of the brain and its expression has been related to long-term quiescent NSC. On the other hand, another cytoskeletal protein, gelsolin, is expressed in Neural Progenitor Cells (NPCs) migrating from the SVZ. Methods: In this study, we intended to investigate by immunocytochemistry the co-expression of GFAP-δ and gelsolin in different sources of hNSCs, and hNPCs, with particular emphasis on Good Manifacture Procedures (GMPs) grade hNSC currently used in two clinical trials on Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) patients. Results: We found that the two proteins are co-expressed by undifferentiated GFAP+ cells but tend to localize in different sub-cellular compartments and to segregate in divergent GFAP+ progenies along with differentiation. Interestingly, we proved that, after transplantation into the brain of rodent models of focal demyelination or transient global ischemia, hNSC integrating in the SVZ still retain the co-expression of GFAP-δ and gelsolin, indicating that hNSC intrinsically co-express the two proteins at the stem stage. Conclusion: These findings suggest that GFAP-δ and gelsolin may represent two candidate markers to distinguish NSC from NSC-deriving divergent astroglial phenotypes. GFAP Delta as Divergent Marker of Human Glial Progenitors Cristina Zalfa1, Chiara Grasselli1, Guido Santilli1, Daniela Ferrari1, Giuseppe Lamorte2, Angelo Luigi Vescovi1,2,3 and Lidia De Filippis3* 1Department of Biotechnologies and Biosciences, Universita’ Milano Bicocca, Piazza della Scienza, Milan, Italy 2Istituto C.S.S. Mendel, Viale Regina Margherita, Roma, Italy 3Casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG), Italy *Corresponding author: Lidia De Filippis, Casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG), Italy, Tel: +39(0882)410346; E-mail: lidia.defilippis@unimib.it; l.defilippis@operapadrepio.it Received August 03, 2018; Accepted September 11, 2018; Published September 17, 2018 Citation: Zalfa C, Grasselli C, Santilli G, Ferrari D, Lamorte G, et al. (2018) GFAP Delta as Divergent Marker of Human Glial Progenitors. Stem Cell Res Ther 8: 437. doi: 10.4172/2157-7633.1000437 Copyright: © 2018 Zalfa C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":"08 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"GFAP Delta as Divergent Marker of Human Glial Progenitors\",\"authors\":\"Cristina Zalfa, C. Grasselli, G. Santilli, D. Ferrari, G. Lamorte, A. Vescovi, L. Filippis\",\"doi\":\"10.4172/2157-7633.1000437\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Human Neural Stem Cells (hNSCs) are responsible for brain development at prenatal and postnatal stages and for tissue homeostasis and repair after injury on adulthood. The identification of hNSC specific markers is still a debated argument. GFAP-δ, the delta isoform of Glial Fibrillary Acidic Protein (GFAP), is particularly expressed in the Subventricular Zone (SVZ) of the brain and its expression has been related to long-term quiescent NSC. On the other hand, another cytoskeletal protein, gelsolin, is expressed in Neural Progenitor Cells (NPCs) migrating from the SVZ. Methods: In this study, we intended to investigate by immunocytochemistry the co-expression of GFAP-δ and gelsolin in different sources of hNSCs, and hNPCs, with particular emphasis on Good Manifacture Procedures (GMPs) grade hNSC currently used in two clinical trials on Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) patients. Results: We found that the two proteins are co-expressed by undifferentiated GFAP+ cells but tend to localize in different sub-cellular compartments and to segregate in divergent GFAP+ progenies along with differentiation. Interestingly, we proved that, after transplantation into the brain of rodent models of focal demyelination or transient global ischemia, hNSC integrating in the SVZ still retain the co-expression of GFAP-δ and gelsolin, indicating that hNSC intrinsically co-express the two proteins at the stem stage. Conclusion: These findings suggest that GFAP-δ and gelsolin may represent two candidate markers to distinguish NSC from NSC-deriving divergent astroglial phenotypes. GFAP Delta as Divergent Marker of Human Glial Progenitors Cristina Zalfa1, Chiara Grasselli1, Guido Santilli1, Daniela Ferrari1, Giuseppe Lamorte2, Angelo Luigi Vescovi1,2,3 and Lidia De Filippis3* 1Department of Biotechnologies and Biosciences, Universita’ Milano Bicocca, Piazza della Scienza, Milan, Italy 2Istituto C.S.S. Mendel, Viale Regina Margherita, Roma, Italy 3Casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG), Italy *Corresponding author: Lidia De Filippis, Casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG), Italy, Tel: +39(0882)410346; E-mail: lidia.defilippis@unimib.it; l.defilippis@operapadrepio.it Received August 03, 2018; Accepted September 11, 2018; Published September 17, 2018 Citation: Zalfa C, Grasselli C, Santilli G, Ferrari D, Lamorte G, et al. (2018) GFAP Delta as Divergent Marker of Human Glial Progenitors. Stem Cell Res Ther 8: 437. doi: 10.4172/2157-7633.1000437 Copyright: © 2018 Zalfa C, et al. 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引用次数: 2
GFAP Delta as Divergent Marker of Human Glial Progenitors
Background: Human Neural Stem Cells (hNSCs) are responsible for brain development at prenatal and postnatal stages and for tissue homeostasis and repair after injury on adulthood. The identification of hNSC specific markers is still a debated argument. GFAP-δ, the delta isoform of Glial Fibrillary Acidic Protein (GFAP), is particularly expressed in the Subventricular Zone (SVZ) of the brain and its expression has been related to long-term quiescent NSC. On the other hand, another cytoskeletal protein, gelsolin, is expressed in Neural Progenitor Cells (NPCs) migrating from the SVZ. Methods: In this study, we intended to investigate by immunocytochemistry the co-expression of GFAP-δ and gelsolin in different sources of hNSCs, and hNPCs, with particular emphasis on Good Manifacture Procedures (GMPs) grade hNSC currently used in two clinical trials on Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) patients. Results: We found that the two proteins are co-expressed by undifferentiated GFAP+ cells but tend to localize in different sub-cellular compartments and to segregate in divergent GFAP+ progenies along with differentiation. Interestingly, we proved that, after transplantation into the brain of rodent models of focal demyelination or transient global ischemia, hNSC integrating in the SVZ still retain the co-expression of GFAP-δ and gelsolin, indicating that hNSC intrinsically co-express the two proteins at the stem stage. Conclusion: These findings suggest that GFAP-δ and gelsolin may represent two candidate markers to distinguish NSC from NSC-deriving divergent astroglial phenotypes. GFAP Delta as Divergent Marker of Human Glial Progenitors Cristina Zalfa1, Chiara Grasselli1, Guido Santilli1, Daniela Ferrari1, Giuseppe Lamorte2, Angelo Luigi Vescovi1,2,3 and Lidia De Filippis3* 1Department of Biotechnologies and Biosciences, Universita’ Milano Bicocca, Piazza della Scienza, Milan, Italy 2Istituto C.S.S. Mendel, Viale Regina Margherita, Roma, Italy 3Casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG), Italy *Corresponding author: Lidia De Filippis, Casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG), Italy, Tel: +39(0882)410346; E-mail: lidia.defilippis@unimib.it; l.defilippis@operapadrepio.it Received August 03, 2018; Accepted September 11, 2018; Published September 17, 2018 Citation: Zalfa C, Grasselli C, Santilli G, Ferrari D, Lamorte G, et al. (2018) GFAP Delta as Divergent Marker of Human Glial Progenitors. Stem Cell Res Ther 8: 437. doi: 10.4172/2157-7633.1000437 Copyright: © 2018 Zalfa C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.