Shared regulatory programs suggest retention of blastula-stage potential in neural crest cells

Buitrago-Delgado, Elsy; Nordin, Kara; Rao, Anjali; Geary, Lauren; LaBonne, Carole

doi:10.1126/science.aaa3655

Cited by 151 publications

(156 citation statements)

References 33 publications

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“…It is also noteworthy that a pool of multipotent postmigratory NC progenitors (47,48), some of which express cKit (49), has been recorded in other tissues; hence, it would be interesting to examine their relationship to CNC kit . Our study differs from a recent cardiac genetic fate-map of cKit, using different cKit alleles (21).…”

Section: Discussionmentioning

confidence: 99%

cKit ⁺ cardiac progenitors of neural crest origin

Hatzistergos¹,

Takeuchi²,

Saur

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

149

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The degree to which cKit-expressing progenitors generate cardiomyocytes in the heart is controversial. Genetic fate-mapping studies suggest minimal contribution; however, whether or not minimal contribution reflects minimal cardiomyogenic capacity is unclear because the embryonic origin and role in cardiogenesis of these progenitors remain elusive. Using high-resolution genetic fate-mapping approaches with cKit CreERT2/+ -induced pluripotent stem cells, we show that, paradoxically, the cardiogenic fate of CNC kit is regulated by bone morphogenetic protein antagonism, a signaling pathway activated transiently during establishment of the cardiac crescent, and extinguished from the heart before CNC invasion. Together, these findings elucidate the origin of cKit + cardiac progenitors and suggest that a nonpermissive cardiac milieu, rather than minimal cardiomyogenic capacity, controls the degree of CNC kit contribution to myocardium.

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Section: Discussionmentioning

confidence: 99%

cKit ⁺ cardiac progenitors of neural crest origin

Hatzistergos¹,

Takeuchi²,

Saur

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

149

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“…This model for extensive cross-talk between Hoxa1 and the pluripotency network may have relevance beyond ES cells. Recent studies in Xenopus have shown that many features of the regulatory program that controls pluripotency in the blastula are also present in neural crest cells (47). Because Hox genes, including Hoxa1, are known to play important roles in formation and patterning of neural crest cells (48,49), they may have a similar cross-regulatory interaction with the pluripotential network in this in vivo context.…”

Section: Resultsmentioning

confidence: 99%

Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells

Kumar

Parker

Parrish

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Homeobox a1 (Hoxa1) is one of the most rapidly induced genes in ES cell differentiation and it is the earliest expressed Hox gene in the mouse embryo. In this study, we used genomic approaches to identify Hoxa1-bound regions during early stages of ES cell differentiation into the neuro-ectoderm. Within 2 h of retinoic acid treatment, Hoxa1 is rapidly recruited to target sites that are associated with genes involved in regulation of pluripotency, and these genes display early changes in expression. The pattern of occupancy of Hoxa1 is dynamic and changes over time. At 12 h of differentiation, many sites bound at 2 h are lost and a new cohort of bound regions appears. At both time points the genome-wide mapping reveals that there is significant co-occupancy of Nanog (Nanog homeobox) and Hoxa1 on many common target sites, and these are linked to genes in the pluripotential regulatory network. In addition to shared target genes, Hoxa1 binds to regulatory regions of Nanog, and conversely Nanog binds to a 3′ enhancer of Hoxa1. This finding provides evidence for direct cross-regulatory feedback between Hoxa1 and Nanog through a mechanism of mutual repression. Hoxa1 also binds to regulatory regions of Sox2 (sex-determining region Y box 2), Esrrb (estrogen-related receptor beta), and Myc, which underscores its key input into core components of the pluripotential regulatory network. We propose a model whereby direct inputs of Nanog and Hoxa1 on shared targets and mutual repression between Hoxa1 and the core pluripotency network provides a molecular mechanism that modulates the fine balance between the alternate states of pluripotency and differentiation.

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“…Their induction and specification begins during the early gastrula stage of development and continues throughout organogenesis. This process depends on multi-module gene regulatory networks acting between the neural plate, non-neural ectoderm and paraxial mesoderm (Buitrago-Delgado et al, 2015;Hoppler and Wheeler, 2015;Huang and Saint-Jeannet, 2004;SaukaSpengler and Bronner-Fraser, 2008). Multiple signals and transcription factors are responsible for neural crest (NC) properties such as multipotency, induction, specification, migration and differentiation (Sauka-Spengler and Bronner-Fraser, 2008).…”

Section: Introductionmentioning

confidence: 97%

The positive transcriptional elongation factor (P-TEFb) is required for neural crest specification

Hatch

Marín-Barba

Moxon

et al. 2016

Developmental Biology

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Regulation of gene expression at the level of transcriptional elongation has been shown to be important in stem cells and tumour cells, but its role in the whole animal is only now being fully explored. Neural crest cells (NCCs) are a multipotent population of cells that migrate during early development from the dorsal neural tube throughout the embryo where they differentiate into a variety of cell types including pigment cells, cranio-facial skeleton and sensory neurons. Specification of NCCs is both spatially and temporally regulated during embryonic development. Here we show that components of the transcriptional elongation regulatory machinery, CDK9 and CYCLINT1 of the P-TEFb complex, are required to regulate neural crest specification. In particular, we show that expression of the proto-oncogene c-Myc and c-Myc responsive genes are affected. Our data suggest that P-TEFb is crucial to drive expression of c-Myc, which acts as a 'gate-keeper' for the correct temporal and spatial development of the neural crest.

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Shared regulatory programs suggest retention of blastula-stage potential in neural crest cells

Cited by 151 publications

References 33 publications

cKit ⁺ cardiac progenitors of neural crest origin

cKit ⁺ cardiac progenitors of neural crest origin

Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells

The positive transcriptional elongation factor (P-TEFb) is required for neural crest specification

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Shared regulatory programs suggest retention of blastula-stage potential in neural crest cells

Cited by 151 publications

References 33 publications

cKit + cardiac progenitors of neural crest origin

cKit + cardiac progenitors of neural crest origin

Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells

The positive transcriptional elongation factor (P-TEFb) is required for neural crest specification

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cKit ⁺ cardiac progenitors of neural crest origin

cKit ⁺ cardiac progenitors of neural crest origin