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A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α
- Source :
- Stem Cells (Dayton, Ohio)
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- In a previous study, we showed that folate receptor‐α (FRα) translocates to the nucleus where it acts as a transcription factor and upregulates Hes1, Oct4, Sox2, and Klf4 genes responsible for pluripotency. Here, we show that acetylation and phosphorylation of FRα favor its nuclear translocation in the presence of folate and can cause a phenotypic switch from differentiated glial cells to dedifferentiated cells. shRNA‐FRα mediated knockdown of FRα was used to confirm the role of FRα in dedifferentiation. Ocimum sanctum hydrophilic fraction‐1 treatment not only blocks the folate mediated dedifferentiation of glial cells but also promotes redifferentiation of dedifferentiated glial cells, possibly by reducing the nuclear translocation of ~38 kDa FRα and subsequent interaction with chromatin assembly factor‐1. stem cells 2019;37:1441–1454<br />Possible mechanisms by which Ocimum sanctum hydrophilic fraction‐1 prevents the formation of folate receptor‐α complex are: (a) the caffeoylquinic acid component of O. sanctum hydrophilic fraction‐1 presumably decreases acetylation of folate receptor‐α by decreasing the acetyl transferase or increasing the deacetylases activity, and subsequent nuclear translocation, and (b) since nuclear folate receptor‐α binds to chromatin assembly factor‐1 in folate‐induced dedifferentiated cells and not in differentiated glial cells, the reduction of folate receptor‐α in the nucleus by O. sanctum hydrophilic fraction‐1 may reactivate chromatin assembly factor‐1 and favor differentiation.
- Subjects :
- 0301 basic medicine
Folate Receptor Alpha
Nuclear Transfer Techniques
Sox2
Oct4
Biology
Tissue‐Specific Stem Cells
Cell Line
Folate receptor alpha
Kruppel-Like Factor 4
03 medical and health sciences
Folic Acid
0302 clinical medicine
SOX2
Cell Line, Tumor
Humans
Folate Receptor 1
RNA, Small Interfering
HES1
Transcription factor
Gene knockdown
SOXB1 Transcription Factors
Cell Biology
Cell Dedifferentiation
Cell biology
030104 developmental biology
Neural Crest
KLF4
Folate receptor
Differentiation
Ocimum sanctum
Molecular Medicine
Dedifferentiation
Cranial neural crest cells
Stem cell
Neuroglia
Octamer Transcription Factor-3
030217 neurology & neurosurgery
Transcription Factors
Developmental Biology
Subjects
Details
- ISSN :
- 15494918 and 10665099
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Stem Cells
- Accession number :
- edsair.doi.dedup.....dc820c38680f650e50e587dc5a318f64