Location of transient ectodermal progenitor potential in mouse development

Li, Lingyu; Liu, Chang; Biechele, Steffen; Zhu, Qingqing; Song, Lu; Lanner, Fredrik; Jing, Naihe; Rossant, Janet

doi:10.1242/dev.092866

Cited by 62 publications

(73 citation statements)

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“…Genetic and embryological studies have revealed that neural induction in the embryo is a multi-step process involving epiblast maturation, ectoderm specification and acquisition of neurectoderm fate (Li et al, 2013;reviewed by Stern, 2005). The identification of the regulatory networks controlling these sequential events has recently benefited from studies highlighting the similarities between the precursors present in the embryo and the in vitro cell types obtained in neural differentiation protocols of stem cells (IwafuchiDoi et al, 2012;Lupo et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…The identification of the regulatory networks controlling these sequential events has recently benefited from studies highlighting the similarities between the precursors present in the embryo and the in vitro cell types obtained in neural differentiation protocols of stem cells (IwafuchiDoi et al, 2012;Lupo et al, 2014). In vivo and in vitro evidence has demonstrated that inhibition of NODAL/ACTIVIN signalling promotes neural fate acquisition in the mouse embryo, as well as during differentiation of mESCs, mouse epiblast stem cells (mEpiSC), and hESCs (Camus et al, 2006;Chng et al, 2010;Li et al, 2013;Patani et al, 2009;Smith et al, 2008;Turner et al, 2014;Vallier et al, 2009;Watanabe et al, 2005). It is tempting to extrapolate that the attenuation of NODAL signalling observed in N1ICD epi embryos from E6.5 contributes to the premature expression of Sox1 in the distal anterior epiblast of these embryos.…”

Section: Discussionmentioning

confidence: 99%

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NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

et al. 2015

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NOTCH signalling is an evolutionarily conserved pathway involved in intercellular communication essential for cell fate choices during development. Although dispensable for early aspects of mouse development, canonical RBPJ-dependent NOTCH signalling has been shown to influence lineage commitment during embryonic stem cell (ESC) differentiation. NOTCH activation in ESCs promotes the acquisition of a neural fate, whereas its suppression favours their differentiation into cardiomyocytes. This suggests that NOTCH signalling is implicated in the acquisition of distinct embryonic fates at early stages of mammalian development. In order to investigate in vivo such a role for NOTCH signalling in shaping cell fate specification, we use genetic approaches to constitutively activate the NOTCH pathway in the mouse embryo. Early embryonic development, including the establishment of anterior-posterior polarity, is not perturbed by forced NOTCH activation. By contrast, widespread NOTCH activity in the epiblast triggers dramatic gastrulation defects. These are fully rescued in a RBPJ-deficient background. Epiblast-specific NOTCH activation induces acquisition of neurectoderm identity and disrupts the formation of specific mesodermal precursors including the derivatives of the anterior primitive streak, the mouse organiser. In addition, we show that forced NOTCH activation results in misregulation of NODAL signalling, a major determinant of early embryonic patterning. Our study reveals a previously unidentified role for canonical NOTCH signalling during mammalian gastrulation. It also exemplifies how in vivo studies can shed light on the mechanisms underlying cell fate specification during in vitro directed differentiation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

et al. 2015

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“…Given that intrinsic regulators, especially TFs, play essential roles in the neural commitment (20,33,34), we sought to identify key TF genes in each of the five modules. By overlapping the stagespecific genes with TF database (35) (www.transcriptionfactor.…”

Section: Regulation Network Of Transcription Factor Genes During Hescmentioning

confidence: 99%

Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells

Wang

Qiao³

et al. 2017

Journal of Biological Chemistry

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Edited by Xiao-Fan WangProper neural commitment is essential for ensuring the appropriate development of the human brain and for preventing neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, and intellectual disorders. However, the molecular mechanisms underlying the neural commitment in humans remain elusive. Here, we report the establishment of a neural differentiation system based on human embryonic stem cells (hESCs) and on comprehensive RNA sequencing analysis of transcriptome dynamics during early hESC differentiation. Using weighted gene co-expression network analysis, we reveal that the hESC neurodevelopmental trajectory has five stages: pluripotency (day 0); differentiation initiation (days 2, 4, and 6); neural commitment (days 8 -10); neural progenitor cell proliferation (days 12, 14, and 16); and neuronal differentiation (days 18, 20, and 22). These stages were characterized by unique module genes, which may recapitulate the early human cortical development. Moreover, a comparison of our RNA-sequencing data with several other transcriptome profiling datasets from mice and humans indicated that Module 3 associated with the day 8 -10 stage is a critical window of fate switch from the pluripotency to the neural lineage. Interestingly, at this stage, no key extrinsic signals were activated. In contrast, using CRISPR/ Cas9 -mediated gene knockouts, we also found that intrinsic hub transcription factors, including the schizophrenia-associated SIX3 gene and septo-optic dysplasia-related HESX1 gene, are required to program hESC neural determination. Our results improve the understanding of the mechanism of neural commitment in the human brain and may help elucidate the etiology of human mental disorders and advance therapies for managing these conditions. Brain development is one of the most complicated and hierarchical events in mammals. A series of temporal processes, including neural commitment, patterning and sub-regionalization, neurogenesis, and neuronal network formation, are required to generate a functional brain (1-4). Defects in any of these processes will lead to neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, depression, and epilepsy. Neural commitment occurs after gastrulation and initiates the program to form neural epithelium (5-7). Many studies on amphibians and rodents reveal that the inhibition of BMP 3 signaling is an evolutionally conserved mechanism for neural induction; in addition, intrinsic factors play pivotal roles to direct fate transition from pluripotency to neural lineage (8 -11). Nonetheless, how the neural commitment is ensured in human brain has not been clearly elucidated. Systematically understanding the critical role of signaling pathways and transcriptional factors in modulating and shaping human brain development is hindered by limited accessibility to early embryos and inadequate amounts of stage-specific and cell type-specific materials. These problems may now be solved by the use of human embryonic stem cells (h...

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“…The lower level of H3ac is observed at the epiblast-like stage of mESC neural differentiation in vitro and in the anterior proximal region of mouse embryos at E7.0 in vivo. Our previous studies revealed that cell populations in the anterior proximal region of mouse embryos at E7.0 possess bipotentiality to form either the surface or the neural ectoderm depending on the local cues 61 . These observations indicate that the transient histone deacetylation most likely participates in the neural fate commitment.…”

Section: Discussionmentioning

confidence: 99%

“…To test this hypothesis, the extra embryonic endoderm (ExE) and visceral endoderm were carefully removed from E7.0 mouse embryos, the epiblast was dissected into the anterior (A) and posterior (P) region, then we cultured the tissues in serum-free medium for 5 days as previously described 61 . After the tissue explants attached for 1 day, the anterior parts displayed homogenous epiblast-like cells with a high nuclear-cytoplasmic ratio; however, the posterior parts generated compact epithelial cells in the centre surrounded by scattered migrating mesodermlike cells (Fig.…”

Section: Article Nature Communications | Doi: 101038/ncomms7830mentioning

confidence: 99%

Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate

et al. 2015

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Cell fate determination requires the cooperation between extrinsic signals and intrinsic molecules including transcription factors as well as epigenetic regulators. Nevertheless, how neural fate commitment is regulated by epigenetic modifications remains largely unclear. Here we show that transient histone deacetylation at epiblast stage promotes neural differentiation of mouse embryonic stem cells (mESCs). Histone deacetylase 1 (HDAC1) deficiency in mESCs partially phenocopies the inhibition of histone deacetylation in vitro, and displays reduced incorporation into neural tissues in chimeric mouse embryos in vivo. Mechanistic studies show that Nodal, which is repressed by histone deacetylation, is a direct target of HDAC1. Furthermore, the inhibition of histone deacetylation in the anterior explant of mouse embryos at E7.0 leads to Nodal activation and neural development repression. Thus, our study reveals an intrinsic mechanism that epigenetic histone deacetylation ensures neural fate commitment by restricting Nodal signalling in murine anterior epiblast ex vivo and mESC in vitro.

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Location of transient ectodermal progenitor potential in mouse development

Cited by 62 publications

References 58 publications

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells

Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate

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