SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells
Само за регистроване кориснике
2014
Аутори
Klajn, AndrijanaDrakulić, Danijela
Tosić, M.
Pavković, Z.
Schwirtlich, Marija
Stevanović, Milena
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
SOX2 is one of the key transcription factors involved in maintenance of neural progenitor identity. However, its function during the process of neural differentiation, including phases of lineage-specification and terminal differentiation, is still poorly understood. Considering growing evidence indicating that SOX2 expression level must be tightly controlled for proper neural development, the aim of this research was to analyze the effects of constitutive SOX2 overexpression on outcome of retinoic acid-induced neural differentiation of pluripotent NT2/D1 cells. We demonstrated that in spite of constitutive SOX2 overexpression, NT2/D1 cells were able to reach final phases of neural differentiation yielding both neuronal and glial cells. However, SOX2 overexpression reduced the number of mature MAP2-positive neurons while no difference in the number of GFAP-positive astrocytes was detected. In-depth analysis at single-cell level showed that SOX2 downregulation was in correlation with bo...th neuronal and glial phenotype acquisitions. Interestingly, while in mature neurons SOX2 was completely downregulated, astrocytes with low level of SOX2 expression were detected. Nevertheless, cells with high level of SOX2 expression were incapable of entering in either of two differentiation pathways, neurogenesis or gliogenesis. Accordingly, our results indicate that fine balance between undifferentiated state and neural differentiation depends on SOX2 expression level. Unlike neurons, astrocytes could maintain low level of SOX2 expression after they acquired glial fate. Further studies are needed to determine whether differences in the level of SOX2 expression in GFAP-positive astrocytes are in correlation with their self-renewal capacity, differentiation status, and/or their phenotypic characteristics.
Кључне речи:
SOX2 overexpression / NT2/D1 / neurogenesis / neural differentiation / gliogenesisИзвор:
Biochemistry-Moscow, 2014, 79, 11, 1172-1182Издавач:
- Maik Nauka/Interperiodica/Springer, New York
Финансирање / пројекти:
- Проучавање сигналних путева и епигенетичких механизама укључених у контролу експресије хуманих SOX гена: даље расветљавање њихове улоге у одређивању судбине и диференцијацији ћелија (RS-MESTD-Basic Research (BR or ON)-173051)
DOI: 10.1134/S0006297914110042
ISSN: 0006-2979
PubMed: 25540002
WoS: 000346565500004
Scopus: 2-s2.0-84919643665
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Klajn, Andrijana AU - Drakulić, Danijela AU - Tosić, M. AU - Pavković, Z. AU - Schwirtlich, Marija AU - Stevanović, Milena PY - 2014 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/735 AB - SOX2 is one of the key transcription factors involved in maintenance of neural progenitor identity. However, its function during the process of neural differentiation, including phases of lineage-specification and terminal differentiation, is still poorly understood. Considering growing evidence indicating that SOX2 expression level must be tightly controlled for proper neural development, the aim of this research was to analyze the effects of constitutive SOX2 overexpression on outcome of retinoic acid-induced neural differentiation of pluripotent NT2/D1 cells. We demonstrated that in spite of constitutive SOX2 overexpression, NT2/D1 cells were able to reach final phases of neural differentiation yielding both neuronal and glial cells. However, SOX2 overexpression reduced the number of mature MAP2-positive neurons while no difference in the number of GFAP-positive astrocytes was detected. In-depth analysis at single-cell level showed that SOX2 downregulation was in correlation with both neuronal and glial phenotype acquisitions. Interestingly, while in mature neurons SOX2 was completely downregulated, astrocytes with low level of SOX2 expression were detected. Nevertheless, cells with high level of SOX2 expression were incapable of entering in either of two differentiation pathways, neurogenesis or gliogenesis. Accordingly, our results indicate that fine balance between undifferentiated state and neural differentiation depends on SOX2 expression level. Unlike neurons, astrocytes could maintain low level of SOX2 expression after they acquired glial fate. Further studies are needed to determine whether differences in the level of SOX2 expression in GFAP-positive astrocytes are in correlation with their self-renewal capacity, differentiation status, and/or their phenotypic characteristics. PB - Maik Nauka/Interperiodica/Springer, New York T2 - Biochemistry-Moscow T1 - SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells EP - 1182 IS - 11 SP - 1172 VL - 79 DO - 10.1134/S0006297914110042 ER -
@article{ author = "Klajn, Andrijana and Drakulić, Danijela and Tosić, M. and Pavković, Z. and Schwirtlich, Marija and Stevanović, Milena", year = "2014", abstract = "SOX2 is one of the key transcription factors involved in maintenance of neural progenitor identity. However, its function during the process of neural differentiation, including phases of lineage-specification and terminal differentiation, is still poorly understood. Considering growing evidence indicating that SOX2 expression level must be tightly controlled for proper neural development, the aim of this research was to analyze the effects of constitutive SOX2 overexpression on outcome of retinoic acid-induced neural differentiation of pluripotent NT2/D1 cells. We demonstrated that in spite of constitutive SOX2 overexpression, NT2/D1 cells were able to reach final phases of neural differentiation yielding both neuronal and glial cells. However, SOX2 overexpression reduced the number of mature MAP2-positive neurons while no difference in the number of GFAP-positive astrocytes was detected. In-depth analysis at single-cell level showed that SOX2 downregulation was in correlation with both neuronal and glial phenotype acquisitions. Interestingly, while in mature neurons SOX2 was completely downregulated, astrocytes with low level of SOX2 expression were detected. Nevertheless, cells with high level of SOX2 expression were incapable of entering in either of two differentiation pathways, neurogenesis or gliogenesis. Accordingly, our results indicate that fine balance between undifferentiated state and neural differentiation depends on SOX2 expression level. Unlike neurons, astrocytes could maintain low level of SOX2 expression after they acquired glial fate. Further studies are needed to determine whether differences in the level of SOX2 expression in GFAP-positive astrocytes are in correlation with their self-renewal capacity, differentiation status, and/or their phenotypic characteristics.", publisher = "Maik Nauka/Interperiodica/Springer, New York", journal = "Biochemistry-Moscow", title = "SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells", pages = "1182-1172", number = "11", volume = "79", doi = "10.1134/S0006297914110042" }
Klajn, A., Drakulić, D., Tosić, M., Pavković, Z., Schwirtlich, M.,& Stevanović, M.. (2014). SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells. in Biochemistry-Moscow Maik Nauka/Interperiodica/Springer, New York., 79(11), 1172-1182. https://doi.org/10.1134/S0006297914110042
Klajn A, Drakulić D, Tosić M, Pavković Z, Schwirtlich M, Stevanović M. SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells. in Biochemistry-Moscow. 2014;79(11):1172-1182. doi:10.1134/S0006297914110042 .
Klajn, Andrijana, Drakulić, Danijela, Tosić, M., Pavković, Z., Schwirtlich, Marija, Stevanović, Milena, "SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells" in Biochemistry-Moscow, 79, no. 11 (2014):1172-1182, https://doi.org/10.1134/S0006297914110042 . .