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WNT inhibition and increased fibroblast growth factor signaling promotes derivation of less heterogeneous primed human embryonic stem cells, compatible with differentiation

Jasin Taelman, Mina Popovic, Monika Bialecka, Laurentijn Tilleman (UGent) , Sharat Warrier, Margot Van der Jeught (UGent) , Björn Menten (UGent) , Dieter Deforce (UGent) , Petra De Sutter (UGent) , Filip Van Nieuwerburgh (UGent) , et al.
(2019) STEM CELLS AND DEVELOPMENT. 28(9). p.579-592
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Abstract
Human embryonic stem cells (hESCs) hold great value for future clinical applications. However, standard culture conditions maintain hESCs in a primed state, which bears heterogeneity in pluripotency and a tendency for spontaneous differentiation. To counter these drawbacks, primed hESCs have been converted to a naive state, but this has restricted the efficiency of existing directed differentiation protocols. In mouse, WNT inhibition by inhibitor of WNT production-2, together with a higher dose of fibroblast growth factor 2 (12 ng/mL) in DMEM/F12 basal medium (DhiFI), markedly improved derivation and maintenance of primed mouse epiblast stem cells. In this study, we show that DhiFI conditions similarly improved primed hESC traits, such as conferring a primed transcriptional signature with high levels of pluripotency markers and reduced levels of differentiation markers. When triggered to differentiate to neuronal and cardiac lineages, DhiFI hESCs and isogenic primed hESCs progressed similarly. Moreover, DhiFI conditions supported the derivation of hESC lines from a post-inner cell mass intermediate (PICMI). DhiFI-derived hESCs showed less spontaneous differentiation and expressed significantly lower levels of lineage-specific markers, compared to primed-derived lines from the same PICMI. Overall, DhiFI hESCs retained advantages of both primed and naive pluripotency and may ultimately represent a more favorable starting point for differentiation toward clinically desired cell types.
Keywords
WNT/BETA-CATENIN, SELF-RENEWAL, NAIVE PLURIPOTENCY, LINES, STATE, MASS, IDENTIFICATION, TRANSITION, TRACKING, ES, human embryonic stem cells, derivation, neuronal, cardiac, transcriptomics

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MLA
Taelman, Jasin, et al. “WNT Inhibition and Increased Fibroblast Growth Factor Signaling Promotes Derivation of Less Heterogeneous Primed Human Embryonic Stem Cells, Compatible with Differentiation.” STEM CELLS AND DEVELOPMENT, vol. 28, no. 9, 2019, pp. 579–92, doi:10.1089/scd.2018.0199.
APA
Taelman, J., Popovic, M., Bialecka, M., Tilleman, L., Warrier, S., Van der Jeught, M., … Chuva de Sousa Lopes, S. M. (2019). WNT inhibition and increased fibroblast growth factor signaling promotes derivation of less heterogeneous primed human embryonic stem cells, compatible with differentiation. STEM CELLS AND DEVELOPMENT, 28(9), 579–592. https://doi.org/10.1089/scd.2018.0199
Chicago author-date
Taelman, Jasin, Mina Popovic, Monika Bialecka, Laurentijn Tilleman, Sharat Warrier, Margot Van der Jeught, Björn Menten, et al. 2019. “WNT Inhibition and Increased Fibroblast Growth Factor Signaling Promotes Derivation of Less Heterogeneous Primed Human Embryonic Stem Cells, Compatible with Differentiation.” STEM CELLS AND DEVELOPMENT 28 (9): 579–92. https://doi.org/10.1089/scd.2018.0199.
Chicago author-date (all authors)
Taelman, Jasin, Mina Popovic, Monika Bialecka, Laurentijn Tilleman, Sharat Warrier, Margot Van der Jeught, Björn Menten, Dieter Deforce, Petra De Sutter, Filip Van Nieuwerburgh, Kuniya Abe, Björn Heindryckx, and Susana Marina Chuva de Sousa Lopes. 2019. “WNT Inhibition and Increased Fibroblast Growth Factor Signaling Promotes Derivation of Less Heterogeneous Primed Human Embryonic Stem Cells, Compatible with Differentiation.” STEM CELLS AND DEVELOPMENT 28 (9): 579–592. doi:10.1089/scd.2018.0199.
Vancouver
1.
Taelman J, Popovic M, Bialecka M, Tilleman L, Warrier S, Van der Jeught M, et al. WNT inhibition and increased fibroblast growth factor signaling promotes derivation of less heterogeneous primed human embryonic stem cells, compatible with differentiation. STEM CELLS AND DEVELOPMENT. 2019;28(9):579–92.
IEEE
[1]
J. Taelman et al., “WNT inhibition and increased fibroblast growth factor signaling promotes derivation of less heterogeneous primed human embryonic stem cells, compatible with differentiation,” STEM CELLS AND DEVELOPMENT, vol. 28, no. 9, pp. 579–592, 2019.
@article{8624388,
  abstract     = {{Human embryonic stem cells (hESCs) hold great value for future clinical applications. However, standard culture conditions maintain hESCs in a primed state, which bears heterogeneity in pluripotency and a tendency for spontaneous differentiation. To counter these drawbacks, primed hESCs have been converted to a naive state, but this has restricted the efficiency of existing directed differentiation protocols. In mouse, WNT inhibition by inhibitor of WNT production-2, together with a higher dose of fibroblast growth factor 2 (12 ng/mL) in DMEM/F12 basal medium (DhiFI), markedly improved derivation and maintenance of primed mouse epiblast stem cells. In this study, we show that DhiFI conditions similarly improved primed hESC traits, such as conferring a primed transcriptional signature with high levels of pluripotency markers and reduced levels of differentiation markers. When triggered to differentiate to neuronal and cardiac lineages, DhiFI hESCs and isogenic primed hESCs progressed similarly. Moreover, DhiFI conditions supported the derivation of hESC lines from a post-inner cell mass intermediate (PICMI). DhiFI-derived hESCs showed less spontaneous differentiation and expressed significantly lower levels of lineage-specific markers, compared to primed-derived lines from the same PICMI. Overall, DhiFI hESCs retained advantages of both primed and naive pluripotency and may ultimately represent a more favorable starting point for differentiation toward clinically desired cell types.}},
  author       = {{Taelman, Jasin and Popovic, Mina and Bialecka, Monika and Tilleman, Laurentijn and Warrier, Sharat and Van der Jeught, Margot and Menten, Björn and Deforce, Dieter and De Sutter, Petra and Van Nieuwerburgh, Filip and Abe, Kuniya and Heindryckx, Björn and Chuva de Sousa Lopes, Susana Marina}},
  issn         = {{1547-3287}},
  journal      = {{STEM CELLS AND DEVELOPMENT}},
  keywords     = {{WNT/BETA-CATENIN,SELF-RENEWAL,NAIVE PLURIPOTENCY,LINES,STATE,MASS,IDENTIFICATION,TRANSITION,TRACKING,ES,human embryonic stem cells,derivation,neuronal,cardiac,transcriptomics}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{579--592}},
  title        = {{WNT inhibition and increased fibroblast growth factor signaling promotes derivation of less heterogeneous primed human embryonic stem cells, compatible with differentiation}},
  url          = {{http://doi.org/10.1089/scd.2018.0199}},
  volume       = {{28}},
  year         = {{2019}},
}
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