Recapitulation of Neural Crest Specification and EMT via Induction from Neural Plate Border-like Cells

Author(s)

Kobayashi, Gerson Shigeru ; Musso, Camila Manso ; Moreira, Danielle de Paula ; Pontillo-Guimaraes, Giovanna ; Hsia, Gabriella Shih Ping ; Caires-Junior, Luiz Carlos ; Goulart, Ernesto ; Passos-Bueno, Maria Rita

• Document type: Journal article
• Source: STEM CELL REPORTS; v. 15, n. 3, p. 13-pg., 2020-09-08.

Abstract

Neural crest cells (NCCs) contribute to several tissues during embryonic development. NCC formation depends on activation of tightly regulated molecular programs at the neural plate border (NPB) region, which initiate NCC specification and epithelial-to-mesenchymal transition (EMT). Although several approaches to investigate NCCs have been devised, these early events of NCC formation remain largely unknown in humans, and currently available cellular models have not investigated EMT. Here, we report that the E6 neural induction protocol converts human induced pluripotent stem cells into NPB-like cells (NBCs), from which NCCs can be efficiently derived. NBC-to-NCC induction recapitulates gene expression dynamics associated with NCC specification and EMT, including downregulation of NPB factors and upregulation of NCC specifiers, coupled with other EMT-associated cell-state changes, such as cadherin modulation and activation of TWIST1 and other EMT inducers. This strategy will be useful in future basic or translational research focusing on these early steps of NCC formation. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/24188-7 - Modelling Richieri-Costa-Pereira Syndrome with the use of induced pluripotent stem cells
• Grantee: Gerson Shigeru Kobayashi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral