Embryonic Stem Cell Culture Conditions Support Distinct States Associated with Different Developmental Stages and Potency

TY - JOUR

T1 - Embryonic Stem Cell Culture Conditions Support Distinct States Associated with Different Developmental Stages and Potency

AU - Martin Gonzalez, Javier

AU - Morgani, Sophie M

AU - Bone, Robert A

AU - Bonderup, Kasper

AU - Abelechian, Sahar

AU - Brakebusch, Cord

AU - Brickman, Joshua M

N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2016/8/9

Y1 - 2016/8/9

N2 - Embryonic stem cells (ESCs) are cell lines derived from the mammalian pre-implantation embryo. Here we assess the impact of derivation and culture conditions on both functional potency and ESC transcriptional identity. Individual ESCs cultured in either two small-molecule inhibitors (2i) or with knockout serum replacement (KOSR), but not serum, can generate high-level chimeras regardless of how these cells were derived. ESCs cultured in these conditions showed a transcriptional correlation with early pre-implantation embryos (E1.5-E3.5) and contributed to development from the 2-cell stage. Conversely, the transcriptome of serum-cultured ESCs correlated with later stages of development (E4.5), at which point embryonic cells are more restricted in their developmental potential. Thus, ESC culture systems are not equivalent, but support cell types that resemble distinct developmental stages. Cells derived in one condition can be reprogrammed to another developmental state merely by adaptation to another culture condition.

AB - Embryonic stem cells (ESCs) are cell lines derived from the mammalian pre-implantation embryo. Here we assess the impact of derivation and culture conditions on both functional potency and ESC transcriptional identity. Individual ESCs cultured in either two small-molecule inhibitors (2i) or with knockout serum replacement (KOSR), but not serum, can generate high-level chimeras regardless of how these cells were derived. ESCs cultured in these conditions showed a transcriptional correlation with early pre-implantation embryos (E1.5-E3.5) and contributed to development from the 2-cell stage. Conversely, the transcriptome of serum-cultured ESCs correlated with later stages of development (E4.5), at which point embryonic cells are more restricted in their developmental potential. Thus, ESC culture systems are not equivalent, but support cell types that resemble distinct developmental stages. Cells derived in one condition can be reprogrammed to another developmental state merely by adaptation to another culture condition.

KW - Journal Article

U2 - 10.1016/j.stemcr.2016.07.009

DO - 10.1016/j.stemcr.2016.07.009

M3 - Journal article

C2 - 27509134

SN - 2213-6711

VL - 7

SP - 177

EP - 191

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 2

ER -