The process by which naïve pre-implantation embryonic stem cells recapitulate in utero progression to post-implantation epiblast has been termed the formative transition. During transition, naïve cells undergo reconfiguration of their transcriptome, epigenome and metabolism to form capacitated cells, fully competent for germ layer induction. Current methods for capacitating human pluripotent stem cells (hPSCs) require prolonged culture that does not reliably recapitulate events in vivo. Now, Austin Smith and colleagues determine the culture conditions for timely hPSC capacitation. The authors confirm that naïve hPSCs do not immediately respond to somatic lineage induction. However, withdrawing self-renewal conditions while inhibiting Wnt signalling allows the cells to gain competence over 7-10 days for efficient differentiation into neuroectoderm, definitive endoderm and paraxial mesoderm lineages. Using comparative bioinformatics, they show that during transition naïve cells follow a developmental trajectory reflective of primate epiblast progression. Finally, they report that capacitated hPSCs can be expanded while showing low or undetectable expression of early lineage markers. These results contribute to our understanding of fundamental concepts in pluripotency and how cells acquire the competence for induction of lineage specification.
Not so naïve: capacitating human stem cells
Not so naïve: capacitating human stem cells. Development 1 April 2019; 146 (7): e0702. doi:
Download citation file:
Advertisement
Cited by
About us

Our publisher, The Company of Biologists, turns 100 this year. Read about the history of the Company and find out what Sarah Bray, our Chair of the Board of Directors, has to say.
Biologists @ 100 - join us in Liverpool in March 2025

We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register by 28 February 2025 to join us in March 2025 in Liverpool, UK.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues

Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology

In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
In preprints
Did you know that Development publishes perspectives on recent preprints? These articles help our readers navigate the ever-growing preprint literature. We welcome proposals for ‘In preprints’ articles, so please do get in touch if you’d like to contribute.