A Single TCF Transcription Factor, Regardless of Its Activation Capacity, Is Sufficient for Effective Trilineage Differentiation of ESCs
Abstract
Co-expression and cross-regulation of the four TCF/LEFs render their redundant and unique functions ambiguous. Here, we describe quadruple-knockout (QKO) mouse ESCs lacking all full-length TCF/LEFs and cell lines rescued with TCF7 or TCF7L1. QKO cells self-renew, despite gene expression patterns that differ significantly from WT, and display delayed, neurectoderm-biased, embryoid body (EB) differentiation. QKO EBs have no contracting cardiomyocytes and differentiate poorly into mesendoderm but readily generate neuronal cells. QKO cells and TCF7L1-rescued cells cannot efficiently activate TCF reporters, whereas TCF7-rescued cells exhibit significant reporter responsiveness. Surprisingly, despite dramatically different transactivation capacities, re-expression of TCF7L1 or TCF7 in QKO cells restores their tri-lineage differentiation ability, with similar lineage marker expression patterns and beating cardiomyocyte frequencies observed in EBs. Both factors also similarly affect the transcriptome of QKO cells. Our data reveal that a single TCF, regardless of its activation capacity, is sufficient for effective trilineage differentiation of ESCs.
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BibTeX
@article{moreira2026single,
title = {{A Single TCF Transcription Factor, Regardless of Its Activation Capacity, Is Sufficient for Effective Trilineage Differentiation of ESCs}},
author = {Steven Moreira and Enio Polena and Victor Gordon and Solen Abdulla and Sujeivan Mahendram and Jiayi Cao and Alexandre Blais and Geoffrey Wood and Anna Dvorkin-Gheva and Bradley Doble},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2017.08.043},
url = {https://hal.science/hal-05794900v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A Single TCF Transcription Factor, Regardless of Its Activation Capacity, Is Sufficient for Effective Trilineage Differentiation of ESCs
AU - Steven Moreira
AU - Enio Polena
AU - Victor Gordon
AU - Solen Abdulla
AU - Sujeivan Mahendram
AU - Jiayi Cao
AU - Alexandre Blais
AU - Geoffrey Wood
AU - Anna Dvorkin-Gheva
AU - Bradley Doble
PY - 2026
DA - 2026/10/12
JO - Cell Reports
DO - 10.1016/j.celrep.2017.08.043
UR - https://hal.science/hal-05794900v1
AB - Co-expression and cross-regulation of the four TCF/LEFs render their redundant and unique functions ambiguous. Here, we describe quadruple-knockout (QKO) mouse ESCs lacking all full-length TCF/LEFs and cell lines rescued with TCF7 or TCF7L1. QKO cells self-renew, despite gene expression patterns that differ significantly from WT, and display delayed, neurectoderm-biased, embryoid body (EB) differentiation. QKO EBs have no contracting cardiomyocytes and differentiate poorly into mesendoderm but readily generate neuronal cells. QKO cells and TCF7L1-rescued cells cannot efficiently activate TCF reporters, whereas TCF7-rescued cells exhibit significant reporter responsiveness. Surprisingly, despite dramatically different transactivation capacities, re-expression of TCF7L1 or TCF7 in QKO cells restores their tri-lineage differentiation ability, with similar lineage marker expression patterns and beating cardiomyocyte frequencies observed in EBs. Both factors also similarly affect the transcriptome of QKO cells. Our data reveal that a single TCF, regardless of its activation capacity, is sufficient for effective trilineage differentiation of ESCs.
SN - 2211-1247
SN - 2211-1247
ER -