Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells
Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. In this study, hPSC lines from multiple donors were differentiated toward neuroectoderm and mesendoderm lineages. We revealed dynamic transcriptomic patterns that delineate the emergence of these lineages, which were conserved across lines, along with individual line-specific transcriptional signatures that were invariant throughout differentiation. These transcriptomic signatures predicted an antagonism between SOX21-driven forebrain fates and retinoic acid-induced hindbrain fates. Replicate lines and paired adult tissue demonstrated the stability of these line-specific transcriptomic traits. We show that this transcriptomic variation in lineage bias had both genetic and epigenetic origins, aligned with the anterior-to-posterior structure of early mammalian development, and was present across a large collection of hPSC lines. These findings contribute to developing systematic analyses of PSCs to define the origin and consequences of variation in the early events orchestrating individual human development.
Authors
- Joshua G. Chenoweth
- Yanhong Wang (ORCID: https://orcid.org/0000-0002-4527-0085)
- Joel E. Kleinman (ORCID: https://orcid.org/0000-0002-4210-6052)
- Roland W. Bürli (ORCID: https://orcid.org/0000-0001-7377-7628)
- Nicola Micali (ORCID: https://orcid.org/0009-0002-2936-4708)
- Nenad Šestan (ORCID: https://orcid.org/0000-0003-0966-9619)
- Elana J. Fertig (ORCID: https://orcid.org/0000-0003-3204-342X)
- Daniel J. Hoeppner (ORCID: https://orcid.org/0000-0002-0886-5215)
- Victor Luria (ORCID: https://orcid.org/0000-0003-0558-0983)
- Joo Heon Shin (ORCID: https://orcid.org/0000-0002-5563-8605)
- Amritha Jaishankar
- Daniel R. Weinberger (ORCID: https://orcid.org/0000-0003-2409-2969)
- A.J. Cross (ORCID: https://orcid.org/0000-0002-2992-2258)
- Thomas M. Hyde (ORCID: https://orcid.org/0000-0002-8746-3037)
- Nicholas J. Brandon (ORCID: https://orcid.org/0000-0002-3917-0096)
- Amir Karger (ORCID: https://orcid.org/0000-0002-4561-3850)
- Genevieve Stein-O’Brien (ORCID: https://orcid.org/0000-0001-8681-9110)
- Carlo Colantuoni (ORCID: https://orcid.org/0000-0001-6818-6380)
- Suel–Kee Kim (ORCID: https://orcid.org/0000-0003-0240-9304)
- Seungmae Seo (ORCID: https://orcid.org/0000-0003-2175-6440)
- Ty C. Voss (ORCID: https://orcid.org/0009-0002-8750-2478)
- Hyojin Kim (ORCID: https://orcid.org/0000-0001-5999-7325)
- Kazuya Ogawa
- Ronald D.G. McKay
Institutions
- AstraZeneca (United Kingdom) (GB)
- University of Maryland, Baltimore (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Yale University (US)
- National Center for Advancing Translational Sciences (US)
- Lieber Institute for Brain Development (US)
Publication Details
- Journal
- Stem Cell Reports
- Published
- 2024-08-15
- DOI
- https://doi.org/10.1016/j.stemcr.2024.07.004
- Citations
- 15
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 3.27
Funders
- Johns Hopkins University
- Lieber Institute for Brain Development
- National Institutes of Health
- National Cancer Institute