Close

Genetically regulated human NODAL splice variants are differentially post-transcriptionally processed and functionally distinct

Scott D Findlay, Olena Bilyk, Kiefer Lypka, Andrew J Waskiewicz, Lynne-Marie Postovit

Posted on: 3 April 2018

Preprint posted on 4 March 2018

Newly discovered human-specific NODAL variant expression downregulates LIFR in human stem cells

Selected by Pierre Osteil

Categories: developmental biology

Background:

NODAL is a growth factor of the TGF-β signalling superfamily that plays critical roles during embryogenesis (particularly in the establishment of left-right asymmetry) and in the maintenance of cancer cells. NODAL has been studied extensively in vertebrate development and in stem cells (1) but this is the first study showing a human-specific splice variant. This article is a follow up study of a previous preprint by the same group (2) relating the discovery of several NODAL splice variants (including an antisense and a circular transcripts) indicating that a lot remains to discover about how NODAL is regulated and affects its targets. Here the authors elucidate a possible function of one of the splice variants that could be involved in the discrepancies observed between naïve and primed embryonic stem cells.

 

The data

In this study, the authors describe one splice variant resulting from a human specific Single Nucleotide Polymorphism (SNP) in the second intron of NODAL (rs2231947 C/T). This intron leads to a transcript that contains a supplementary exon and a Premature Termination Codon, resulting in the translation of a distinct protein. Using morpholinos, they were able to inhibit specifically this variant in human embryonic stem cells (hESC), which led to an increase of Leukemia Inhibitory Factor Receptor (LIFR). Its expression is generally shut down in hESC conversely to mouse species. Both constitutive and human-specific transcripts were injected into zebrafish embryos to assess canonical NODAL signalling activity. While the constitutive NODAL injection leads to a disruption of gastrulation, the variant did not, suggesting different action mechanisms. Moreover, the alternative splicing of NODAL leads to partial disruption of the TGB-β superfamily domain that may impact on NODAL signalling.

Finally, the authors found that the two proteins are differently N-glycosylated, resulting in an increased level of excretion of the variant protein compared to the constitutive NODAL. Differential secretion may thus partially explain their different functions.

Image reproduced from Findlay et al., 2018 Fig 3A and 3B

 

Why did I choose this article?

The newly described NODAL variant could be responsible for the loss of LIFR observed in primed ESCs of non-murine species. The SNP is specific to the human genome and might explain why human stem cells cannot be stabilised at the naïve state of pluripotency. My PhD project was articulated around the understanding of naïve versus primed pluripotency, and I highlighted this article for the clues it gives toward deciphering pluripotency regulatory mechanisms.

 

Open questions

  • Have you checked hESC pluripotency status when the NODAL variant is knocked down? Could you observe upregulation of genes associated to naïve pluripotency?
  • Is this variant present in other mammals such as rabbit or monkey? If yes, you might be able to link the presence of this variant to the impossibility of establishing naïve pluripotency in non-murine mammals?

 

Related research

  1. Pauklin S, Vallier L (2015) Activin/Nodal signalling in stem cells. Development 142(4):607–619.
  2. Findlay SD, Postovit L-M (2018) Comprehensive characterization of transcript diversity at the human NODAL locus. bioRxiv:1–26.

 

Tags: hesc, naive, nodal, primed, stem cell

Read preprint (No Ratings Yet)

Have your say

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

Also in the developmental biology category:

Notch3 is a genetic modifier of NODAL signalling for patterning asymmetry during mouse heart looping

Tobias Holm Bønnelykke, Marie-Amandine Chabry, Emeline Perthame, et al.

Selected by 06 June 2024

Bhaval Parmar

Developmental Biology

Lipid-Based Transfection of Zebrafish Embryos: A Robust Protocol for Nucleic Acid Delivery

Aslihan Terzi, Tiger Liao, Adrian Jacobo

Selected by 09 May 2024

Roberto Rodríguez-Morales

Genetics

Topology changes of the regenerating Hydra define actin nematic defects as mechanical organizers of morphogenesis

Yamini Ravichandran, Matthias Vogg, Karsten Kruse, et al.

Selected by 08 May 2024

Rachel Mckeown

Developmental Biology

preLists in the developmental biology category:

BSDB/GenSoc Spring Meeting 2024

A list of preprints highlighted at the British Society for Developmental Biology and Genetics Society joint Spring meeting 2024 at Warwick, UK.

 



List by Joyce Yu, Katherine Brown

GfE/ DSDB meeting 2024

This preList highlights the preprints discussed at the 2024 joint German and Dutch developmental biology societies meeting that took place in March 2024 in Osnabrück, Germany.

 



List by Joyce Yu

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

2nd Conference of the Visegrád Group Society for Developmental Biology

Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)

 



List by Nándor Lipták

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020

 



List by Jesus Victorino

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.

 



List by Alex Eve

Society for Developmental Biology 79th Annual Meeting

Preprints at SDB 2020

 



List by Irepan Salvador-Martinez, Martin Estermann

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EDBC Alicante 2019

Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.

 



List by Sergio Menchero et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.

 



List by Alex Eve

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London

 



List by Alex Eve

Pattern formation during development

The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.

 



List by Alexa Sadier

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.

 



List by Shikha Nayar
Close