Suel-Kee Kim, Seungmae Seo, Genevieve Stein-O'Brien, Amritha Jaishankar, Kazuya Ogawa, Nicola Micali, Victor Luria, Amir Karger, Yanhong Wang, Hyojin Kim, Thomas M Hyde, Joel E Kleinman, Ty Voss, Elana J Fertig, Joo-Heon Shin, Roland Bürli, Alan J Cross, Nicholas J Brandon, Daniel R Weinberger, Joshua G Chenoweth, Daniel J Hoeppner, Nenad Sestan, Carlo Colantuoni, Ronald D McKay
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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.
期刊介绍:
Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.