Title: Towards reconstituting human & primate early embryonic development
in vitro
Date: Friday, October 11, 17:00-
Venue: Bldg.3-South, 1F ENEOS Hall
Affiliation: Institute for the Advanced Study of Human Biology (ASHBi), Kyoto
University, Kyoto, Japan
Abstract:
Recent efforts to reconstruct complex developmental processes in vitro from stem cells
open up exciting new opportunities for studying the biological principles, which govern
the emergence of form and function during embryonic development in humans and
other non-model organisms. Early embryonic developmental events including
somitogenesis, during which the metameric body plan of vertebrates is laid out, have
been extensively studied using model organisms such as mouse or chick but remain
largely elusive and poorly understood when it comes to human and other primates.
Using induced pluripotent stem cell (iPSC)-derived presomitic mesoderm (PSM), we
previously succeeded to quantify oscillatory activity of the segmentation clock, a
molecular oscillator believed to control segmentation process (Matsuda, Yamanaka et
al., Nature 2020; Matsuda et al., Science 2020). Interestingly, these in vitro models of
the segmentation clock did not show any sign of segmentation or somitogenesis
despite the presence of oscillatory activity of clock genes such as HES7. Extending on
these earlier findings we then asked whether we could recapitulate not only the clock
but also the actual process of segmentation and epithelial somite formation in vitro.
Utilizing again pluripotent stem cells as starting material we succeeded to establish a
3D in vitro model of human somitogenesis, which exhibited periodic formation of
properly patterned epithelial somites in synchrony with the segmentation clock
(Yamanaka, Hamidi et al., Nature 2022). Our selforganizing ‘axioloids’ reconstituted
various morphological and molecular features of the emerging human embryonic axis
and could be also used to study the pathogenesis of human congenital diseases of the
spine. Currently, we are continuing to improve and utilize axioloids and other in vitro
models of embryonic development to increase our still limited understanding of
development and disease in human and other primates.
Short Bio of Prof. Cantas Alev:
Dr. Alev is a principal investigator and tenured professor at the Institute
for the Advanced Study of Human Biology (ASHBi) in Kyoto University.
Together with his team at ASHBi he studies various aspects of early
human embryonic development using stem cell-based model systems.
Establishing and utilizing a variety of human and other species in vitro
model systems of embryonic development & organogenesis, his lab at
ASHBi aims to increase our still limited understanding of our own
species’ biology, including human development, disease and evolution.
Dr. Alev did his postdoctoral work at the RIKEN Center for Developmental
Biology (RIKEN CDB) in the laboratory of Dr. Guojun Sheng on
gastrulation and post-gastrulation development focusing on mesoderm
induction and patterning. During his subsequent tenure at the Center for
iPS Cell Research and Application (CiRA) he used his insights into
embryonic development to establish & study pluripotent stem cell-based
models of human mesoderm development & differentiation, including in
vitro models of the segmentation clock and diseases of the spine. In his
lab at ASHBi Dr. Alev continues to work on ethically non-controversial in
vitro models which can reconstitute defined aspects of human
development in a dish.