Transcriptional Heterogeneity in Naive and Primed Human Pluripotent Stem Cells at Single-Cell Resolution

TY - JOUR

T1 - Transcriptional Heterogeneity in Naive and Primed Human Pluripotent Stem Cells at Single-Cell Resolution

AU - Messmer, Tobias

AU - von Meyenn, Ferdinand

AU - Savino, Aurora

AU - Santos, Fátima

AU - Mohammed, Hisham

AU - Lun, Aaron Tin Long

AU - Marioni, John C

AU - Reik, Wolf

N1 - Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

PY - 2019/1/22

Y1 - 2019/1/22

N2 - Conventional human embryonic stem cells are considered to be primed pluripotent but can be induced to enter a naive state. However, the transcriptional features associated with naive and primed pluripotency are still not fully understood. Here we used single-cell RNA sequencing to characterize the differences between these conditions. We observed that both naive and primed populations were mostly homogeneous with no clear lineage-related structure and identified an intermediate subpopulation of naive cells with primed-like expression. We found that the naive-primed pluripotency axis is preserved across species, although the timing of the transition to a primed state is species specific. We also identified markers for distinguishing human naive and primed pluripotency as well as strong co-regulatory relationships between lineage markers and epigenetic regulators that were exclusive to naive cells. Our data provide valuable insights into the transcriptional landscape of human pluripotency at a cellular and genome-wide resolution.

AB - Conventional human embryonic stem cells are considered to be primed pluripotent but can be induced to enter a naive state. However, the transcriptional features associated with naive and primed pluripotency are still not fully understood. Here we used single-cell RNA sequencing to characterize the differences between these conditions. We observed that both naive and primed populations were mostly homogeneous with no clear lineage-related structure and identified an intermediate subpopulation of naive cells with primed-like expression. We found that the naive-primed pluripotency axis is preserved across species, although the timing of the transition to a primed state is species specific. We also identified markers for distinguishing human naive and primed pluripotency as well as strong co-regulatory relationships between lineage markers and epigenetic regulators that were exclusive to naive cells. Our data provide valuable insights into the transcriptional landscape of human pluripotency at a cellular and genome-wide resolution.

UR - http://www.scopus.com/inward/record.url?scp=85059824819&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.12.099

DO - 10.1016/j.celrep.2018.12.099

M3 - Article

C2 - 30673604

SN - 2211-1247

VL - 26

SP - 815

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -