Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity.

<h4>Background</h4>Neural conversion from human embryonic stem cells (hESCs) has been demonstrated in a variety of systems including chemically defined suspension culture, not requiring extrinsic signals, as well as in an adherent culture method that involves dual SMAD inhibition using N...

Full description

Saved in:
Bibliographic Details
Main Authors: Rickie Patani, Alastair Compston, Clare A Puddifoot, David J A Wyllie, Giles E Hardingham, Nicholas D Allen, Siddharthan Chandran
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-10-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007327&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849467935939100672
author Rickie Patani
Alastair Compston
Clare A Puddifoot
David J A Wyllie
Giles E Hardingham
Nicholas D Allen
Siddharthan Chandran
author_facet Rickie Patani
Alastair Compston
Clare A Puddifoot
David J A Wyllie
Giles E Hardingham
Nicholas D Allen
Siddharthan Chandran
author_sort Rickie Patani
collection DOAJ
description <h4>Background</h4>Neural conversion from human embryonic stem cells (hESCs) has been demonstrated in a variety of systems including chemically defined suspension culture, not requiring extrinsic signals, as well as in an adherent culture method that involves dual SMAD inhibition using Noggin and SB431542 (an inhibitor of activin/nodal signaling). Previous studies have also determined a role for activin/nodal signaling in development of the neural plate and anterior fate specification. We therefore sought to investigate the independent influence of SB431542 both on neural commitment of hESCs and positional identity of derived neural progenitors in chemically defined substrate-free conditions.<h4>Methodology/principal findings</h4>We show that in non-adherent culture conditions, treatment with SB431542 alone for 8 days is sufficient for highly efficient and accelerated neural conversion from hESCs with negligible mesendodermal, epidermal or trophectodermal contamination. In addition the resulting neural progenitor population has a predominantly caudal identity compared to the more anterior positional fate of non-SB431542 treated cultures. Finally we demonstrate that resulting neurons are electro-physiologically competent.<h4>Conclusions</h4>This study provides a platform for the efficient generation of caudal neural progenitors under defined conditions for experimental study.
format Article
id doaj-art-e6aec00108374ac9a30074b8675a9ea2
institution Kabale University
issn 1932-6203
language English
publishDate 2009-10-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-e6aec00108374ac9a30074b8675a9ea22025-08-20T03:25:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-10-01410e732710.1371/journal.pone.0007327Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity.Rickie PataniAlastair CompstonClare A PuddifootDavid J A WyllieGiles E HardinghamNicholas D AllenSiddharthan Chandran<h4>Background</h4>Neural conversion from human embryonic stem cells (hESCs) has been demonstrated in a variety of systems including chemically defined suspension culture, not requiring extrinsic signals, as well as in an adherent culture method that involves dual SMAD inhibition using Noggin and SB431542 (an inhibitor of activin/nodal signaling). Previous studies have also determined a role for activin/nodal signaling in development of the neural plate and anterior fate specification. We therefore sought to investigate the independent influence of SB431542 both on neural commitment of hESCs and positional identity of derived neural progenitors in chemically defined substrate-free conditions.<h4>Methodology/principal findings</h4>We show that in non-adherent culture conditions, treatment with SB431542 alone for 8 days is sufficient for highly efficient and accelerated neural conversion from hESCs with negligible mesendodermal, epidermal or trophectodermal contamination. In addition the resulting neural progenitor population has a predominantly caudal identity compared to the more anterior positional fate of non-SB431542 treated cultures. Finally we demonstrate that resulting neurons are electro-physiologically competent.<h4>Conclusions</h4>This study provides a platform for the efficient generation of caudal neural progenitors under defined conditions for experimental study.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007327&type=printable
spellingShingle Rickie Patani
Alastair Compston
Clare A Puddifoot
David J A Wyllie
Giles E Hardingham
Nicholas D Allen
Siddharthan Chandran
Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity.
PLoS ONE
title Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity.
title_full Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity.
title_fullStr Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity.
title_full_unstemmed Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity.
title_short Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity.
title_sort activin nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007327&type=printable
work_keys_str_mv AT rickiepatani activinnodalinhibitionaloneaccelerateshighlyefficientneuralconversionfromhumanembryonicstemcellsandimposesacaudalpositionalidentity
AT alastaircompston activinnodalinhibitionaloneaccelerateshighlyefficientneuralconversionfromhumanembryonicstemcellsandimposesacaudalpositionalidentity
AT clareapuddifoot activinnodalinhibitionaloneaccelerateshighlyefficientneuralconversionfromhumanembryonicstemcellsandimposesacaudalpositionalidentity
AT davidjawyllie activinnodalinhibitionaloneaccelerateshighlyefficientneuralconversionfromhumanembryonicstemcellsandimposesacaudalpositionalidentity
AT gilesehardingham activinnodalinhibitionaloneaccelerateshighlyefficientneuralconversionfromhumanembryonicstemcellsandimposesacaudalpositionalidentity
AT nicholasdallen activinnodalinhibitionaloneaccelerateshighlyefficientneuralconversionfromhumanembryonicstemcellsandimposesacaudalpositionalidentity
AT siddharthanchandran activinnodalinhibitionaloneaccelerateshighlyefficientneuralconversionfromhumanembryonicstemcellsandimposesacaudalpositionalidentity