Acquisition of neural fate by combination of BMP blockade and chromatin modification

Ong, Agnes Lee Chen; Kokaji, Toshiya; Kishi, Arisa; Takihara, Yoshihiro; Shinozuka, Takuma; Shimamoto, Ren; Isotani, Ayako; Shirai, Manabu; Sasai, Noriaki

doi:10.1016/j.isci.2023.107887

Cited by 2 publications

(1 citation statement)

References 122 publications

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“…The development of NNE requires not only induction signals but also the inhibition of mesendoderm-promoting genes [4]. BMP signaling has been demonstrated to be crucial for ectodermal patterning and the inhibition of NE fate [5,6]. While the TGFβ/Activin/Nodal pathway is known to induce mesoderm and endoderm fate [7].…”

Section: Introductionmentioning

confidence: 99%

Small Molecules Promote the Rapid Generation of Dental Epithelial Cells from Human-Induced Pluripotent Stem Cells

Zhu,

Li,

Dong

et al. 2024

IJMS

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Human-induced pluripotent stem cells (hiPSCs) offer a promising source for generating dental epithelial (DE) cells. Whereas the existing differentiation protocols were time-consuming and relied heavily on growth factors, herein, we developed a three-step protocol to convert hiPSCs into DE cells in 8 days. In the first phase, hiPSCs were differentiated into non-neural ectoderm using SU5402 (an FGF signaling inhibitor). The second phase involved differentiating non-neural ectoderm into pan-placodal ectoderm and simultaneously inducing the formation of oral ectoderm (OE) using LDN193189 (a BMP signaling inhibitor) and purmorphamine (a SHH signaling activator). In the final phase, OE cells were differentiated into DE through the application of Purmorphamine, XAV939 (a WNT signaling inhibitor), and BMP4. qRT-PCR and immunostaining were performed to examine the expression of lineage-specific markers. ARS staining was performed to evaluate the formation of the mineralization nodule. The expression of PITX2, SP6, and AMBN, the emergence of mineralization nodules, and the enhanced expression of AMBN and AMELX in spheroid culture implied the generation of DE cells. This study delineates the developmental signaling pathways and uses small molecules to streamline the induction of hiPSCs into DE cells. Our findings present a simplified and quicker method for generating DE cells, contributing valuable insights for dental regeneration and dental disease research.

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