Random migration of induced pluripotent stem cell-derived human gastrulation-stage mesendoderm

Yuta Yamamoto, Shota Miyazaki, Kenshiro Maruyama, Ryo Kobayashi, Minh Nguyen Tuyet Le, Ayumu Kano, Akiko Kondo, Shuji Fujii, Kiyoshi Ohnuma

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Gastrulation is the initial systematic deformation of the embryo to form germ layers, which is characterized by the placement of appropriate cells in their destined locations. Thus, gastrulation, which occurs at the beginning of the second month of pregnancy, is a critical stage in human body formation. Although histological analyses indicate that human gastrulation is similar to that of other amniotes (birds and mammals), much of human gastrulation dynamics remain unresolved due to ethical and technical limitations. We used human induced pluripotent stem cells (hiPSCs) to study the migration of mesendodermal cells through the primitive streak to form discoidal germ layers during gastrulation. Immunostaining results showed that hiPSCs differentiated into mesendodermal cells and that epithelial–mesenchymal transition occurred through the activation of the Activin/Nodal and Wnt/beta-catenin pathways. Single-cell time-lapse imaging of cells adhered to cover glass showed that mesendodermal differentiation resulted in the dissociation of cells and an increase in their migration speed, thus confirming the occurrence of epithelial–mesenchymal transition. These results suggest that mesendodermal cells derived from hiPSCs may be used as a model system for studying migration during human gastrulation in vitro. Using random walk analysis, we found that random migration occurred for both undifferentiated hiPSCs and differentiated mesendodermal cells. Two-dimensional random walk simulation showed that homogeneous dissociation of particles may form a discoidal layer, suggesting that random migration might be suitable to effectively disperse cells homogeneously from the primitive streak to form discoidal germ layers during human gastrulation.

Original languageEnglish
Article numbere0201960
JournalPloS one
Volume13
Issue number9
DOIs
Publication statusPublished - 01-09-2018

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Induced Pluripotent Stem Cells
Gastrulation
Stem cells
Germ Layers
Primitive Streak
cells
Activins
Mammals
beta Catenin
Birds
Chemical activation
Cells
Time-Lapse Imaging
activins
Imaging techniques
Glass
gastrulation
induced pluripotent stem cells
Human Body
cell movement

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Yamamoto, Y., Miyazaki, S., Maruyama, K., Kobayashi, R., Le, M. N. T., Kano, A., ... Ohnuma, K. (2018). Random migration of induced pluripotent stem cell-derived human gastrulation-stage mesendoderm. PloS one, 13(9), [e0201960]. https://doi.org/10.1371/journal.pone.0201960
Yamamoto, Yuta ; Miyazaki, Shota ; Maruyama, Kenshiro ; Kobayashi, Ryo ; Le, Minh Nguyen Tuyet ; Kano, Ayumu ; Kondo, Akiko ; Fujii, Shuji ; Ohnuma, Kiyoshi. / Random migration of induced pluripotent stem cell-derived human gastrulation-stage mesendoderm. In: PloS one. 2018 ; Vol. 13, No. 9.
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Yamamoto, Y, Miyazaki, S, Maruyama, K, Kobayashi, R, Le, MNT, Kano, A, Kondo, A, Fujii, S & Ohnuma, K 2018, 'Random migration of induced pluripotent stem cell-derived human gastrulation-stage mesendoderm', PloS one, vol. 13, no. 9, e0201960. https://doi.org/10.1371/journal.pone.0201960

Random migration of induced pluripotent stem cell-derived human gastrulation-stage mesendoderm. / Yamamoto, Yuta; Miyazaki, Shota; Maruyama, Kenshiro; Kobayashi, Ryo; Le, Minh Nguyen Tuyet; Kano, Ayumu; Kondo, Akiko; Fujii, Shuji; Ohnuma, Kiyoshi.

In: PloS one, Vol. 13, No. 9, e0201960, 01.09.2018.

Research output: Contribution to journalArticle

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AU - Yamamoto, Yuta

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AU - Le, Minh Nguyen Tuyet

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AU - Kondo, Akiko

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AU - Ohnuma, Kiyoshi

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Yamamoto Y, Miyazaki S, Maruyama K, Kobayashi R, Le MNT, Kano A et al. Random migration of induced pluripotent stem cell-derived human gastrulation-stage mesendoderm. PloS one. 2018 Sep 1;13(9). e0201960. https://doi.org/10.1371/journal.pone.0201960