A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α

Sarah Monick; Vineet Mohanty; Mariam Khan; Gowtham Yerneni; Raj Kumar; Jorge Cantu; Shunsuke Ichi; Guifa Xi; Bal Ram Singh; Tadanori Tomita; Chandra Shekhar Mayanil

doi:10.1002/stem.3067

A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α

Sarah Monick, Vineet Mohanty, Mariam Khan, Gowtham Yerneni, Raj Kumar, Jorge Cantu, Shunsuke Ichi, Guifa Xi, Bal Ram Singh, Tadanori Tomita, Chandra Shekhar Mayanil^*

^*Corresponding author for this work

Neurological Surgery

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	1441-1454
Number of pages	14
Journal	Stem Cells
Volume	37
Issue number	11
DOIs	https://doi.org/10.1002/stem.3067
State	Published - Nov 1 2019

Keywords

Cranial neural crest cells
Dedifferentiation
Differentiation
Folate receptor alpha
Oct4
Sox2

ASJC Scopus subject areas

Molecular Medicine
Developmental Biology
Cell Biology

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@article{67b884044b124e37acaac3792bfd5f21,

title = "A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α",

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.",

keywords = "Cranial neural crest cells, Dedifferentiation, Differentiation, Folate receptor alpha, Oct4, Sox2",

author = "Sarah Monick and Vineet Mohanty and Mariam Khan and Gowtham Yerneni and Raj Kumar and Jorge Cantu and Shunsuke Ichi and Guifa Xi and Singh, {Bal Ram} and Tadanori Tomita and Mayanil, {Chandra Shekhar}",

note = "Funding Information: Thanks are due to Peggy A. Murphy and Barbara Mania-Farnell for critically reading the manuscript, and Dr. C. David James and Dr. John A. Kessler for very fruitful discussion. This work was supported in part by the State of Illinois Excellence in Academic Medicine award (C.S.M.); a grant from the Spastic Paralysis Research Foundation of Illinois-Eastern Iowa District of Kiwanis (C.S.M.); the Spina Bifida Association and Stanley Manne Children's Research Institute Pilot Grant award (C.S.M.); Eleanor Clarke Chair in Developmental Neurobiology (C.S.M.); and Neurofibromatosis fund from the Division of Pediatric Neurosurgery, Ann & Robert H. Lurie Children's Hospital of Chicago. We thank Bio-Rad for their generous gift of Trans-Blot Turbo and the ChemiDocMP system.",

year = "2019",

month = nov,

day = "1",

doi = "10.1002/stem.3067",

language = "English (US)",

volume = "37",

pages = "1441--1454",

journal = "Stem Cells",

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A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α. / Monick, Sarah; Mohanty, Vineet; Khan, Mariam; Yerneni, Gowtham; Kumar, Raj; Cantu, Jorge; Ichi, Shunsuke; Xi, Guifa; Singh, Bal Ram; Tomita, Tadanori; Mayanil, Chandra Shekhar.

In: Stem Cells, Vol. 37, No. 11, 01.11.2019, p. 1441-1454.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α

AU - Monick, Sarah

AU - Mohanty, Vineet

AU - Khan, Mariam

AU - Yerneni, Gowtham

AU - Kumar, Raj

AU - Cantu, Jorge

AU - Ichi, Shunsuke

AU - Xi, Guifa

AU - Singh, Bal Ram

AU - Tomita, Tadanori

AU - Mayanil, Chandra Shekhar

N1 - Funding Information: Thanks are due to Peggy A. Murphy and Barbara Mania-Farnell for critically reading the manuscript, and Dr. C. David James and Dr. John A. Kessler for very fruitful discussion. This work was supported in part by the State of Illinois Excellence in Academic Medicine award (C.S.M.); a grant from the Spastic Paralysis Research Foundation of Illinois-Eastern Iowa District of Kiwanis (C.S.M.); the Spina Bifida Association and Stanley Manne Children's Research Institute Pilot Grant award (C.S.M.); Eleanor Clarke Chair in Developmental Neurobiology (C.S.M.); and Neurofibromatosis fund from the Division of Pediatric Neurosurgery, Ann & Robert H. Lurie Children's Hospital of Chicago. We thank Bio-Rad for their generous gift of Trans-Blot Turbo and the ChemiDocMP system.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

KW - Cranial neural crest cells

KW - Dedifferentiation

KW - Differentiation

KW - Folate receptor alpha

KW - Oct4

KW - Sox2

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SN - 1066-5099

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