Uncovering the mesendoderm gene regulatory network through multi-omic data integration

Jansen, Camden; Paraiso, Kitt D.; Zhou, Jeff Jiajing; Blitz, Ira L.; Fish, Margaret; Charney, Rebekah M.; Cho, Jin Sun; Yasuoka, Yoshifumi; Sudou, Norihiro; Bright, Ann Rose; Wlizla, Marcin; Veenstra, G.J.C.; Taira, Masanori; Zorn, Aaron M.; Mortazavi, A; Cho, Ken W.Y.

doi:10.1016/j.celrep.2022.110364

Cited by 12 publications

(11 citation statements)

References 88 publications

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“…The mesendoderm gene regulatory network (GRN) has been extensively studied and has yielded a significant “parts list” of genes that make significant contributions to the formation of these lineages [ 106 , 107 ], however the ordering of the GRN components has lacked the temporal resolution that our time series data can provide. Accordingly, we examined the expression of forty-one validated mesendoderm GRN components across both the endoderm and ventral mesoderm lineage trajectories (Fig.…”

Section: Resultsmentioning

confidence: 99%

Quantitative analysis of transcriptome dynamics provides novel insights into developmental state transitions

et al. 2022

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Background During embryogenesis, the developmental potential of initially pluripotent cells becomes progressively restricted as they transit to lineage restricted states. The pluripotent cells of Xenopus blastula-stage embryos are an ideal system in which to study cell state transitions during developmental decision-making, as gene expression dynamics can be followed at high temporal resolution. Results Here we use transcriptomics to interrogate the process by which pluripotent cells transit to four different lineage-restricted states: neural progenitors, epidermis, endoderm and ventral mesoderm, providing quantitative insights into the dynamics of Waddington’s landscape. Our findings provide novel insights into why the neural progenitor state is the default lineage state for pluripotent cells and uncover novel components of lineage-specific gene regulation. These data reveal an unexpected overlap in the transcriptional responses to BMP4/7 and Activin signaling and provide mechanistic insight into how the timing of signaling inputs such as BMP are temporally controlled to ensure correct lineage decisions. Conclusions Together these analyses provide quantitative insights into the logic and dynamics of developmental decision making in early embryos. They also provide valuable lineage-specific time series data following the acquisition of specific lineage states during development.

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Section: Resultsmentioning

confidence: 99%

Quantitative analysis of transcriptome dynamics provides novel insights into developmental state transitions

et al. 2022

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“…FGF/MAPK signaling activity is required for the induction of both ectoderm and mesendoderm lineages, as well as for further lineage-restricted decisions (e.g., neural and neural crest cell fate; axial/paraxial mesodermal fate) [ 81 , 89 , 90 , 91 ]. Recently, several studies point out the fundamental function of chromatin organization and poised enhancers, which represent distal regulatory elements that control the expression of major developmental genes, during the process of embryonic cell commitment and the establishment of stable epigenetic memory, which signs the exit from pluripotency state at the onset of gastrulation [ 68 , 69 , 70 , 92 , 93 , 94 ].…”

Section: Role Of Developmental Potential Guardians In Stem Cells Plur...mentioning

confidence: 99%

Vertebrate Cell Differentiation, Evolution, and Diseases: The Vertebrate-Specific Developmental Potential Guardians VENTX/NANOG and POU5/OCT4 Enter the Stage

Ducos

Bensimon

Scerbo

2022

Cells

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During vertebrate development, embryonic cells pass through a continuum of transitory pluripotent states that precede multi-lineage commitment and morphogenesis. Such states are referred to as “refractory/naïve” and “competent/formative” pluripotency. The molecular mechanisms maintaining refractory pluripotency or driving the transition to competent pluripotency, as well as the cues regulating multi-lineage commitment, are evolutionarily conserved. Vertebrate-specific “Developmental Potential Guardians” (vsDPGs; i.e., VENTX/NANOG, POU5/OCT4), together with MEK1 (MAP2K1), coordinate the pluripotency continuum, competence for multi-lineage commitment and morphogenesis in vivo. During neurulation, vsDPGs empower ectodermal cells of the neuro-epithelial border (NEB) with multipotency and ectomesenchyme potential through an “endogenous reprogramming” process, giving rise to the neural crest cells (NCCs). Furthermore, vsDPGs are expressed in undifferentiated-bipotent neuro-mesodermal progenitor cells (NMPs), which participate in posterior axis elongation and growth. Finally, vsDPGs are involved in carcinogenesis, whereby they confer selective advantage to cancer stem cells (CSCs) and therapeutic resistance. Intriguingly, the heterogenous distribution of vsDPGs in these cell types impact on cellular potential and features. Here, we summarize the findings about the role of vsDPGs during vertebrate development and their selective advantage in evolution. Our aim to present a holistic view regarding vsDPGs as facilitators of both cell plasticity/adaptability and morphological innovation/variation. Moreover, vsDPGs may also be at the heart of carcinogenesis by allowing malignant cells to escape from physiological constraints and surveillance mechanisms.

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“…This is associated with reduced accessibility at Wnt-responsive promoters [ 47 ]. Integration of ChIP-seq, ATAC-seq and transcriptomics data using machine learning uncovered novel TFs involved in mesendoderm formation during Xenopus gastrulation [ 48 ].…”

Section: Early Events: Gastrulation Germ Layer Formation and Axis Pat...mentioning

confidence: 99%

Investigating chromatin accessibility during development and differentiation by ATAC-sequencing to guide the identification of cis-regulatory elements

Smith

Mok

Münsterberg

2022

Biochemical Society Transactions

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Mapping accessible chromatin across time scales can give insights into its dynamic nature, for example during cellular differentiation and tissue or organism development. Analysis of such data can be utilised to identify functional cis-regulatory elements (CRE) and transcription factor binding sites and, when combined with transcriptomics, can reveal gene regulatory networks (GRNs) of expressed genes. Chromatin accessibility mapping is a powerful approach and can be performed using ATAC-sequencing (ATAC-seq), whereby Tn5 transposase inserts sequencing adaptors into genomic DNA to identify differentially accessible regions of chromatin in different cell populations. It requires low sample input and can be performed and analysed relatively quickly compared with other methods. The data generated from ATAC-seq, along with other genomic approaches, can help uncover chromatin packaging and potential cis-regulatory elements that may be responsible for gene expression. Here, we describe the ATAC-seq approach and give examples from mainly vertebrate embryonic development, where such datasets have identified the highly dynamic nature of chromatin, with differing landscapes between cellular precursors for different lineages.

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Uncovering the mesendoderm gene regulatory network through multi-omic data integration

Cited by 12 publications

References 88 publications

Quantitative analysis of transcriptome dynamics provides novel insights into developmental state transitions

Quantitative analysis of transcriptome dynamics provides novel insights into developmental state transitions

Vertebrate Cell Differentiation, Evolution, and Diseases: The Vertebrate-Specific Developmental Potential Guardians VENTX/NANOG and POU5/OCT4 Enter the Stage

Investigating chromatin accessibility during development and differentiation by ATAC-sequencing to guide the identification of cis-regulatory elements

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