Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions

Sophie M. Morgani, Maurice A. Canham, Jennifer Nichols, Alexei A. Sharov, RosaPortero Migueles, Minoru Ko, Joshua M. Brickman

Research output: Contribution to journalArticle

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Abstract

Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all lineages, to pluripotency, when they are competent to make only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) are thought to represent an embryonically restricted ground state. However, we observed heterogeneous expression of the extraembryonic endoderm marker Hex in 2i-cultured embryos, suggesting that 2i blocked development prior to epiblast commitment. Similarly, 2i ESC cultures were heterogeneous and contained a Hex-positive fraction primed to differentiate into trophoblast and extraembryonic endoderm. Single Hex-positive ESCs coexpressed epiblast and extraembryonic genes and contributed to all lineages in chimeras. The cytokine LIF, necessary for ESC self-renewal, supported the expansion of this population but did not directly support Nanog-positive epiblast-like ESCs. Thus, 2i and LIF support a totipotent state comparable to early embryonic cells that coexpress embryonic and extraembryonic determinants.

Original languageEnglish
Pages (from-to)1945-1957
Number of pages13
JournalCell Reports
Volume3
Issue number6
DOIs
Publication statusPublished - 2013 Mar 27

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Totipotent Stem Cells
Embryonic Stem Cells
Stem cells
Cell culture
Ground state
Germ Layers
Endoderm
Mammalian Embryo
Blastomeres
Mitogen-Activated Protein Kinase Kinases
Trophoblasts
Embryonic Structures
Cell Culture Techniques
Genes
Cytokines

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Morgani, S. M., Canham, M. A., Nichols, J., Sharov, A. A., Migueles, R., Ko, M., & Brickman, J. M. (2013). Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions. Cell Reports, 3(6), 1945-1957. https://doi.org/10.1016/j.celrep.2013.04.034

Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions. / Morgani, Sophie M.; Canham, Maurice A.; Nichols, Jennifer; Sharov, Alexei A.; Migueles, RosaPortero; Ko, Minoru; Brickman, Joshua M.

In: Cell Reports, Vol. 3, No. 6, 27.03.2013, p. 1945-1957.

Research output: Contribution to journalArticle

Morgani, SM, Canham, MA, Nichols, J, Sharov, AA, Migueles, R, Ko, M & Brickman, JM 2013, 'Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions', Cell Reports, vol. 3, no. 6, pp. 1945-1957. https://doi.org/10.1016/j.celrep.2013.04.034
Morgani SM, Canham MA, Nichols J, Sharov AA, Migueles R, Ko M et al. Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions. Cell Reports. 2013 Mar 27;3(6):1945-1957. https://doi.org/10.1016/j.celrep.2013.04.034
Morgani, Sophie M. ; Canham, Maurice A. ; Nichols, Jennifer ; Sharov, Alexei A. ; Migueles, RosaPortero ; Ko, Minoru ; Brickman, Joshua M. / Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions. In: Cell Reports. 2013 ; Vol. 3, No. 6. pp. 1945-1957.
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