Human axial progenitors generate trunk neural crest cells in vitro

Frith, Thomas J.R.; Granata, Ilaria; Wind, Matthew; Stout, Erin; Thompson, Oliver; Neumann, Katrin; Stavish, Dylan; Heath, Paul R.; Ortmann, Daniel; Hackland, James; Anastassiadis, Konstantinos; Gouti, Mina; Briscoe, James; Wilson, Valerie; Johnson, Stuart L.; Placzek, Marysia; Guarracino, Mario Rosario; Andrews, Peter W.; Tsakiridis, Anestis

doi:10.7554/elife.35786

Cited by 94 publications

(189 citation statements)

References 115 publications

Supporting

Mentioning

162

Contrasting

Order By: Relevance

“…Avian studies have reported that RA participates in NC migration, and possibly formation (Martínez-Morales et al, 2011), but murine knockout models affecting RA signaling still form NC (Dupé and Pellerin, 2009;Niederreither et al, 2000). Here, we find that, similar to other reports (Fattahi et al, 2016;Frith et al, 2018;Fukuta et al, 2014;Huang et al, 2016;Mica et al, 2013), exogenous RA can posteriorize NCs during maturation stages. However, early addition of RA prevents NC specification.…”

Section: Putative Additional Players Triggered By Chir99021supporting

confidence: 92%

“…The co-expression of TBXT along with SOX2 defines neuromesodermal progenitors (NMPs) that contribute to posterior axial tissues, including spinal cord and mesoderm (Henrique et al, 2015). Importantly, NMPs have also been suggested to contribute to NCC formation (Cambray and Wilson, 2007;McGrew et al, 2008;Wymeersch et al, 2016), and recently NCs have been generated from NMPs (Frith et al, 2018). Therefore, we evaluated the expression of SOX2 and TBXT in high-WNT cultures.…”

Section: Posterior Nccs Transiently Express An Nmp-like Precursor Promentioning

confidence: 99%

See 1 more Smart Citation

WNT/β-CATENIN modulates the axial identity of ES derived human neural crest

et al. 2019

Self Cite

View full text Add to dashboard Cite

WNT/β-catenin signaling is crucial for neural crest (NC) formation, yet the effects of the magnitude of the WNT signal remain ill-defined. Using a robust model of human NC formation based on human pluripotent stem cells (hPSCs), we expose that the WNT signal modulates the axial identity of NCs in a dose-dependent manner, with low WNT leading to anterior OTX + HOX − NC and high WNT leading to posterior OTX − HOX + NC. Differentiation tests of posterior NC confirm expected derivatives, including posterior-specific adrenal derivatives, and display partial capacity to generate anterior ectomesenchymal derivatives. Furthermore, unlike anterior NC, posterior NC exhibits a transient TBXT + /SOX2 + neuromesodermal precursor-like intermediate. Finally, we analyze the contributions of other signaling pathways in posterior NC formation, which suggest a crucial role for FGF in survival/proliferation, and a requirement of BMP for NC maturation. As expected retinoic acid (RA) and FGF are able to modulate HOX expression in the posterior NC. Surprisingly, early RA supplementation prohibits NC formation. This work reveals for the first time that the amplitude of WNT signaling can modulate the axial identity of NC cells in humans.

show abstract

Section: Putative Additional Players Triggered By Chir99021supporting

confidence: 92%

Section: Posterior Nccs Transiently Express An Nmp-like Precursor Promentioning

confidence: 99%

WNT/β-CATENIN modulates the axial identity of ES derived human neural crest

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…It was recently shown that NMPs produced from hPSCs in vitro have the potential to generate NCCs (Frith et al, 2018), and in a manuscript submitted elsewhere by Hackland et al we have found that posterior NC generated in a xeno-free (BSA free, and using N2 instead of B27 supplement, and under modulated BMP) platform are also derived from a similar axial progenitor. Some recent evidence from lineage tracing experiments in chick and mice favor the contribution of NMPs to NCCs (Cambray and Wilson, 2007; McGrew et al, 2008; Wymeersch et al, 2016).…”

Section: Discussionmentioning

confidence: 68%

WNT/β-CATENIN modulates the axial identity of ES derived human neural crest

Gomez¹,

Prasad²,

Wong³

et al. 2019

Preprint

View full text Add to dashboard Cite

8The WNT/β-CATENIN pathway is critical for neural crest (NC) formation. However, the effects of the 1 9 magnitude of the signal remains poorly defined. Here we evaluate the consequences of WNT 2 0 magnitude variation in a robust model of human NC formation. This model is based on human 2 1 embryonic stem cells induced by WNT signaling through the small molecule CHIR9902. In addition 2 2 to its known effect on NC formation, we find that the WNT signal modulates the anterior-posterior 2 3 axial identity of NCCs in a dose dependent manner, with low WNT leading to anterior OTX+, HOX-2 4 NC, and high WNT leading to posterior OTX-, HOX+ NC. Differentiation tests of posterior NC confirm 2 5 expected derivatives including posterior specific adrenal derivatives, and display partial capacity to 2 6 generate anterior ectomesenchymal derivatives. Furthermore, unlike anterior NC, posterior NC 2 7 transit through a TBXT+/SOX2+ neuromesodermal precursor-like intermediate. Finally, we analyze 2 8 the contributions of other signaling pathways in posterior NC formation, and suggest a critical role for 2 9 FGF in survival/proliferation, and a requirement of BMP for NC maturation. As expected RA and 3 0 FGF are able to modulate HOX expression in the posterior NC, but surprisingly, RA supplementation 3 1 prohibits anterior, but only reduces, posterior NC formation. This work reveals for the first time that 3 2 the amplitude of WNT signaling can modulate the axial identity of NC cells in humans. 3 3 3 4 KEY WORDS: neural crest, WNT dosage/magnitude, anterior-posterior axis, HOX genes, 3 5 human embryonic stem cells.

show abstract

“…HOX genes define the tempo of the induction (Bel-Vialar et al, 2002;Del Corral and Storey, 30 2004;Deschamps and Duboule, 2017;Ebisuya and Briscoe, 2018;Lippmann et al, 2015;31 Mazzoni et al, 2013;Wymeersch et al, 2019). This might result in the current limited control 32 over pluripotent stem cells (PSCs) differentiation into caudal cell types of distinct well-defined 33 rostro-caudal identities (Diaz-Cuadros et al, 2020;Du et al, 2015;Duval et al, 2019;Faustino 34 Martins et al, 2020;Frith et al, 2018;Gouti et al, 2014;Li et al, 2005;Lippmann et al, 2015;35 Matsuda et al, 2020;Maury et al, 2015;Ogura et al, 2018;Peljto et al, 2010;Verrier et al, 36 2018). Indeed, the two models imply different strategies to control in vitro PSC differentiation.…”

Section: Introduction 15mentioning

confidence: 99%

Dynamic extrinsic pacing of theHOXclock in human axial progenitors controls motor neuron subtype specification

Mouilleau

Vaslin

Gribaudo

et al. 2020

Preprint

View full text Add to dashboard Cite

Rostro-caudal patterning of vertebrates depends on the temporally progressive activation of HOX 1 genes within axial stem cells that fuel axial embryo elongation. Whether HOX genes sequential 2 activation, the "HOX clock", is paced by intrinsic chromatin-based timing mechanisms or by 3 temporal changes in extrinsic cues remains unclear. Here, we studied HOX clock pacing in 4 human pluripotent stem cells differentiating into spinal cord motor neuron subtypes which are 5 progenies of axial progenitors. We show that the progressive activation of caudal HOX genes in 6 axial progenitors is controlled by a dynamic increase in FGF signaling. Blocking FGF pathway 7 stalled induction of HOX genes, while precocious increase in FGF alone, or with GDF11 ligand, 8 accelerated the HOX clock. Cells differentiated under accelerated HOX induction generated 9 appropriate posterior motor neuron subtypes found along the human embryonic spinal cord. The 10 HOX clock is thus dynamically paced by exposure parameters to secreted cues. Its manipulation 11 by extrinsic factors alleviates temporal requirements to provide unprecedented synchronized 12 access to human cells of multiple, defined, rostro-caudal identities for basic and translational 13 applications. , et al. (2013). Accelerated highyield generation of limb-innervating motor neurons from human stem cells. J. Neurosci. 33, 574-586. ., et al. (2019). Stem cell-derived cranial and spinal motor neurons reveal proteostatic differences between ALS resistant and sensitive motor neurons. Elife 8,.

show abstract

Human axial progenitors generate trunk neural crest cells in vitro

Cited by 94 publications

References 115 publications

WNT/β-CATENIN modulates the axial identity of ES derived human neural crest

WNT/β-CATENIN modulates the axial identity of ES derived human neural crest

WNT/β-CATENIN modulates the axial identity of ES derived human neural crest

Dynamic extrinsic pacing of theHOXclock in human axial progenitors controls motor neuron subtype specification

Contact Info

Product

Resources

About