Modulating Mesendoderm Competence During Human Germ Layer Differentiation

Valcourt, James R.; Huang, Roya; Kundu, Sharmistha; Venkatasubramanian, Divya; Kingston, Robert E.; Ramanathan, Sharad

doi:10.2139/ssrn.3813289

Cited by 2 publications

(3 citation statements)

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“…A popular recent approach based in the Waddington landscape metaphor has been shown to be a powerful yet simple way to study cell fate transitions in different contexts (Camacho-Aguilar et al, 2021; Coomer et al, 2022; Corson and Siggia, 2012; Corson and Siggia, 2017; Huang, 2012; Mojtahedi et al, 2016; Sáez et al, 2022; Valcourt et al, 2021). In these models, the differentiation of a cell is depicted as ball rolling down a landscape of hills and valleys, that represent the different cell types the stem cell can differentiate into.…”

Section: Discussionmentioning

confidence: 99%

Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration

Camacho-Aguilar

Yoon

Ortiz-Salazar

et al. 2022

Preprint

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Secreted morphogen signals play a key role in the determination of cell fates during embryonic development. BMP signaling is essential for vertebrate gastrulation, as it initiates a cascade of signals that controls the self-organized patterning of the three germ layers. Although morphogen signals are typically thought to induce cell fates in a concentration-dependent manner, development is a highly dynamic process, so it is crucial to understand how time-dependent signaling affects cellular differentiation. Here we show that varying the duration of BMP signaling leads to either pluripotent, mesodermal, and extraembryonic states, while varying the concentration does not cause efficient mesodermal differentiation at any dose. Thus, there is a morphogen effect in time but not in concentration, and an appropriately timed pulse of BMP induces hPSCs to a mesodermal fate more efficiently that sustained signaling at any concentration. Using live cell imaging of signaling and cell fate reporters together with a simple mathematical model, we show that this effect is due to a combinatorial interpretation of the applied BMP signal and induced endogenous WNT signaling. Our findings have implications for how signaling pathways control the landscape of early human development.

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Section: Discussionmentioning

confidence: 99%

Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration

Camacho-Aguilar

Yoon

Ortiz-Salazar

et al. 2022

Preprint

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“…Taking this into account, it appears that the function of zebrafish and Xenopus Pou5f3 in neurogenesis is an evolutionary inherited feature. The Pou5f1 orthologue (Oct4), which is present in mammals, has probably lost this feature, as it acts primarily in pluripotency control [5] and mesendoderm development [137,150]. Nevertheless, murine ESCs, which harbour only this Pou5f1 orthologue, are characterized by epithelial morphology, E-cadherin expression, and the default capacity for neuroectodermal differentiation [157].…”

Section: Discussionmentioning

confidence: 99%

“…At initial steps of specification of both mouse and human ESCs, Sox2 and Oct4 levels are strongly predictive of subsequent ME and NE fate—i.e. before the expression of corresponding markers [136,137]. During differentiation of mouse ESCs, Oct4 suppresses the NE state and does not colocalize with Sox1, while Sox2 antagonizes ME (Brachyury+) specification.…”

Section: Biological Functions Of the Pouv Proteins In Amniotesmentioning

confidence: 99%

The functional diversity of the POUV-class proteins across vertebrates

Bakhmet

Tomilin

2022

Open Biol.

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POUV is a relatively newly emerged class of POU transcription factors present in jawed vertebrates (Gnathostomata). The function of POUV-class proteins is inextricably linked to zygotic genome activation (ZGA). A large body of evidence now extends the role of these proteins to subsequent developmental stages. While some functions resemble those of other POU-class proteins and are related to neuroectoderm development, others have emerged de novo . The most notable of the latter functions is pluripotency control by Oct4 in mammals. In this review, we focus on these de novo functions in the best-studied species harbouring POUV proteins—zebrafish, Xenopus (anamniotes) and mammals (amniotes). Despite the broad diversity of their biological functions in vertebrates, POUV proteins exert a common feature related to their role in safeguarding the undifferentiated state of cells. Here we summarize numerous pieces of evidence for these specific functions of the POUV-class proteins and recap available loss-of-function data.

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Modulating Mesendoderm Competence During Human Germ Layer Differentiation

Cited by 2 publications

References 0 publications

Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration

Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration

The functional diversity of the POUV-class proteins across vertebrates

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