TY - JOUR
KW - Cell Differentiation
KW - Cell Line
KW - Cell Lineage
KW - Epigenesis, Genetic
KW - Gene Expression Regulation, Developmental
KW - Humans
KW - Pluripotent Stem Cells
KW - SOX21
KW - Transcriptome
KW - Tretinoin
KW - acid signaling
KW - anterior or posterior neural fates
KW - cell line variation
KW - early embryo
KW - human population
KW - Pluripotent Stem Cells
KW - retinoic
AU - Suel-Kee Kim
AU - Seungmae Seo
AU - Genevieve Stein-O'Brien
AU - Amritha Jaishankar
AU - Kazuya Ogawa
AU - Nicola Micali
AU - Victor Luria
AU - Amir Karger
AU - Yanhong Wang
AU - Hyojin Kim
AU - Thomas M. Hyde
AU - Joel E. Kleinman
AU - Ty Voss
AU - Elana J. Fertig
AU - Joo-Heon Shin
AU - Roland Bürli
AU - Alan J. Cross
AU - Nicholas J. Brandon
AU - Daniel R. Weinberger
AU - Joshua G. Chenoweth
AU - Daniel J. Hoeppner
AU - Nenad Sestan
AU - Carlo Colantuoni
AU - Ronald D. McKay
AB - 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.
BT - Stem Cell Reports
DA - 2024-09-10
DO - 10.1016/j.stemcr.2024.07.004
IS - 9
LA - eng
N2 - 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.
PY - 2024
SP - 1336
EP - 1350
T2 - Stem Cell Reports
TI - Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells
VL - 19
SN - 2213-6711
ER -