Critical roles of FGF, RA, and WNT signalling in the development of the human otic placode and subsequent lineages in a dish

Saeki, Tsubasa; Yoshimatsu, Sho; Ishikawa, Mitsuru; Hon, Chung-Chau; Koya, Ikuko; Shibata, Shinsuke; Saegusa, Chika; Ogawa, Kaoru; Shin, Jay W.; Fujioka, Masato

doi:10.1016/j.reth.2022.04.008

Cited by 7 publications

(6 citation statements)

References 76 publications

(117 reference statements)

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“…We then queried the data for the expression of different sets of markers for embryonic and extra-embryonic lineages that appear in early human development. Table S1 shows the lists of gene sets we curated from published data [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] . We found NE 1q showed high levels of expression of markers of non-central nervous system (non-CNS) ectodermal lineages such as non-neural ectoderm and of cranial placode (Fig.…”

Section: Resultsmentioning

confidence: 99%

Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity

Spits,

Krivec,

de Deckersberg

et al. 2023

Preprint

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Gains of 1q are a highly recurrent chromosomal abnormality in human pluripotent stem cells. In this work, we show that gains of 1q impact the differentiation capacity to derivates of the three germ layers, leading to miss-specification to cranial placode and non-neural ectoderm during neuroectoderm differentiation and by poorer expression of lineage specific markers in hepatoblasts and cardiac progenitors. Competition assays show that the cells retain their selective advantage during differentiation, which is mediated by a higher expression of MDM4, a gene located in the common region of gain. MDM4 drives the winner phenotype of the mutant cells in both the undifferentiated and differentiating state by reducing the cells’ sensitivity to DNA-damage through decreased p53-mediated apoptosis. Finally, we find that cell density in culture plays a key role in promoting the competitive advantage of the cells by increasing DNA damage.

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Section: Resultsmentioning

confidence: 99%

Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity

Spits,

Krivec,

de Deckersberg

et al. 2023

Preprint

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show abstract

Section: Nementioning

confidence: 99%

Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity

Krivec,

Couvreu de Deckersberg,

Lei

et al. 2023

Preprint

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Gains of 1q are a highly recurrent chromosomal abnormality in human pluripotent stem cells. In this work, we show that gains of 1q impact the differentiation capacity to derivates of the three germ layers, leading to miss-specification to cranial placode and non-neural ectoderm during neuroectoderm differentiation and by poorer expression of lineage specific markers in hepatoblasts and cardiac progenitors. Competition assays show that the cells retain their selective advantage during differentiation, which is mediated by a higher expression of MDM4, a gene located in the common region of gain. MDM4 drives the winner phenotype of the mutant cells in both the undifferentiated and differentiating state by reducing the cells sensitivity to DNA-damage through decreased p53-mediated apoptosis. Finally, we find that cell density in culture plays a key role in promoting the competitive advantage of the cells by increasing DNA damage.

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“…A very recent publication by Saeki and colleagues (2022) describes a protocol that benefits from a monolayer culture format where transient BMP signalling and TGFβ inhibition efficiently lead to hESC differentiation into PPE, while further differentiation of these cultures to a posterior placode fate is carried out in 3D cultures [ 56 ]. Heterogeneity of the starting cell population is thus reduced, while the 3D culture system is meant to counteract the tendency of 2D cultures to promote anterior placode fates and reduce the efficiency of downstream differentiation protocols towards otic placodal lineages.…”

Section: Hipsc-based Cultures To Model Inner Ear Developmentmentioning

confidence: 99%

“…However, they have also reported heterogeneous cell cultures as well as failed attempts to maintain JAG+/SOX2+ prosensory cells in culture and to differentiate them to HC-like cells; such differentiation was only attained when these cultures were forced to overexpress ATOH1, POU4F3 and GFI1, three factors that have been shown to induce the differentiation of mESCs into HC-like cells [ 57 ]. These data underline the difficulties that accompany the establishment of efficient differentiation protocols; there may be “contaminating” non-target cell populations that provide inductive signals and trophic support to the differentiating otic precursors; although these populations hinder the elucidation of factors that drive the differentiation steps, they cannot be removed from the culture while such factors remain unknown [ 49 , 56 ].…”

Section: Hipsc-based Cultures To Model Inner Ear Developmentmentioning

confidence: 99%

“…Following up on their recent publication [ 56 ], Kurihara and co-workers (2022) have described a stepwise protocol to produce hiPSC-derived SGN-like cells that integrates 2D and 3D cultures [ 50 ]. hiPSCs are initially grown as monolayers in the presence of FGFs, a transient activation of the BMP pathway and a posterior WNT activation, giving rise to homogeneous OP cultures; GFs are then removed, and the cells are shortly grown under hypoxic conditions.…”

Section: Hipsc-based Cultures To Model Inner Ear Developmentmentioning

confidence: 99%

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Induced Pluripotent Stem Cells, a Stepping Stone to In Vitro Human Models of Hearing Loss

Alonso

Petković

2022

Cells

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Hearing loss is the most prevalent sensorineural impairment in humans. Yet despite very active research, no effective therapy other than the cochlear implant has reached the clinic. Main reasons for this failure are the multifactorial nature of the disorder, its heterogeneity, and a late onset that hinders the identification of etiological factors. Another problem is the lack of human samples such that practically all the work has been conducted on animals. Although highly valuable data have been obtained from such models, there is the risk that inter-species differences exist that may compromise the relevance of the gathered data. Human-based models are therefore direly needed. The irruption of human induced pluripotent stem cell technologies in the field of hearing research offers the possibility to generate an array of otic cell models of human origin; these may enable the identification of guiding signalling cues during inner ear development and of the mechanisms that lead from genetic alterations to pathology. These models will also be extremely valuable when conducting ototoxicity analyses and when exploring new avenues towards regeneration in the inner ear. This review summarises some of the work that has already been conducted with these cells and contemplates future possibilities.

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Critical roles of FGF, RA, and WNT signalling in the development of the human otic placode and subsequent lineages in a dish

Cited by 7 publications

References 76 publications

Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity

Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity

Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity

Induced Pluripotent Stem Cells, a Stepping Stone to In Vitro Human Models of Hearing Loss

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