Examining the role of the surfactant family member SFTA3 in interneuron specification.

The transcription factor NKX2.1, expressed at high levels in the medial ganglionic eminence (MGE), is a master regulator of cortical interneuron progenitor development. To identify gene candidates with expression profiles similar to NKX2.1, previous transcriptome analysis of human embryonic stem cel...

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Main Authors: Christopher Y Chen, Nickesha C Anderson, Sandy Becker, Martin Schicht, Christopher Stoddard, Lars Bräuer, Friedrich Paulsen, Laura Grabel
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC6224035?pdf=render
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author Christopher Y Chen
Nickesha C Anderson
Sandy Becker
Martin Schicht
Christopher Stoddard
Lars Bräuer
Friedrich Paulsen
Laura Grabel
author_facet Christopher Y Chen
Nickesha C Anderson
Sandy Becker
Martin Schicht
Christopher Stoddard
Lars Bräuer
Friedrich Paulsen
Laura Grabel
author_sort Christopher Y Chen
collection DOAJ
description The transcription factor NKX2.1, expressed at high levels in the medial ganglionic eminence (MGE), is a master regulator of cortical interneuron progenitor development. To identify gene candidates with expression profiles similar to NKX2.1, previous transcriptome analysis of human embryonic stem cell (hESC)-derived MGE-like progenitors revealed SFTA3 as the strongest candidate. Quantitative real-time PCR analysis of hESC-derived NKX2.1-positive progenitors and transcriptome data available from the Allen Institute for Brain Science revealed comparable expression patterns for NKX2.1 and SFTA3 during interneuron differentiation in vitro and demonstrated high SFTA3 expression in the human MGE. Although SFTA3 has been well studied in the lung, the possible role of this surfactant protein in the MGE during embryonic development remains unexamined. To determine if SFTA3 plays a role in MGE specification, SFTA3-/- and NKX2.1 -/- hESC lines were generated using custom designed CRISPRs. We show that NKX2.1 KOs have a significantly diminished capacity to differentiate into MGE interneuron subtypes. SFTA3 KOs also demonstrated a somewhat reduced ability to differentiate down the MGE-like lineage, although not as severe relative to NKX2.1 deficiency. These results suggest NKX2.1 and SFTA3 are co-regulated genes, and that deletion of SFTA3 does not lead to a major change in the specification of MGE derivatives.
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spelling doaj.art-85bd819e3f144649ac08ed52836206e02022-12-22T01:48:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011311e019870310.1371/journal.pone.0198703Examining the role of the surfactant family member SFTA3 in interneuron specification.Christopher Y ChenNickesha C AndersonSandy BeckerMartin SchichtChristopher StoddardLars BräuerFriedrich PaulsenLaura GrabelThe transcription factor NKX2.1, expressed at high levels in the medial ganglionic eminence (MGE), is a master regulator of cortical interneuron progenitor development. To identify gene candidates with expression profiles similar to NKX2.1, previous transcriptome analysis of human embryonic stem cell (hESC)-derived MGE-like progenitors revealed SFTA3 as the strongest candidate. Quantitative real-time PCR analysis of hESC-derived NKX2.1-positive progenitors and transcriptome data available from the Allen Institute for Brain Science revealed comparable expression patterns for NKX2.1 and SFTA3 during interneuron differentiation in vitro and demonstrated high SFTA3 expression in the human MGE. Although SFTA3 has been well studied in the lung, the possible role of this surfactant protein in the MGE during embryonic development remains unexamined. To determine if SFTA3 plays a role in MGE specification, SFTA3-/- and NKX2.1 -/- hESC lines were generated using custom designed CRISPRs. We show that NKX2.1 KOs have a significantly diminished capacity to differentiate into MGE interneuron subtypes. SFTA3 KOs also demonstrated a somewhat reduced ability to differentiate down the MGE-like lineage, although not as severe relative to NKX2.1 deficiency. These results suggest NKX2.1 and SFTA3 are co-regulated genes, and that deletion of SFTA3 does not lead to a major change in the specification of MGE derivatives.http://europepmc.org/articles/PMC6224035?pdf=render
spellingShingle Christopher Y Chen
Nickesha C Anderson
Sandy Becker
Martin Schicht
Christopher Stoddard
Lars Bräuer
Friedrich Paulsen
Laura Grabel
Examining the role of the surfactant family member SFTA3 in interneuron specification.
PLoS ONE
title Examining the role of the surfactant family member SFTA3 in interneuron specification.
title_full Examining the role of the surfactant family member SFTA3 in interneuron specification.
title_fullStr Examining the role of the surfactant family member SFTA3 in interneuron specification.
title_full_unstemmed Examining the role of the surfactant family member SFTA3 in interneuron specification.
title_short Examining the role of the surfactant family member SFTA3 in interneuron specification.
title_sort examining the role of the surfactant family member sfta3 in interneuron specification
url http://europepmc.org/articles/PMC6224035?pdf=render
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