Transcription factor co-expression mediates lineage priming for embryonic and extra-embryonic differentiation
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Transcription factor co-expression mediates lineage priming for embryonic and extra-embryonic differentiation. / Redó-Riveiro, Alba; Al-Mousawi, Jasmina; Linneberg-Agerholm, Madeleine; Proks, Martin; Perera, Marta; Salehin, Nazmus; Brickman, Joshua M.
In: Stem Cell Reports, Vol. 19, No. 2, 2024, p. 174-186.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Transcription factor co-expression mediates lineage priming for embryonic and extra-embryonic differentiation
AU - Redó-Riveiro, Alba
AU - Al-Mousawi, Jasmina
AU - Linneberg-Agerholm, Madeleine
AU - Proks, Martin
AU - Perera, Marta
AU - Salehin, Nazmus
AU - Brickman, Joshua M.
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2024
Y1 - 2024
N2 - In early mammalian development, cleavage stage blastomeres and inner cell mass (ICM) cells co-express embryonic and extra-embryonic transcriptional determinants. Using a protein-based double reporter we identify an embryonic stem cell (ESC) population that co-expresses the extra-embryonic factor GATA6 alongside the embryonic factor SOX2. Based on single cell transcriptomics, we find this population resembles the unsegregated ICM, exhibiting enhanced differentiation potential for endoderm while maintaining epiblast competence. To relate transcription factor binding in these cells to future fate, we describe a complete enhancer set in both ESCs and naive extra-embryonic endoderm stem cells and assess SOX2 and GATA6 binding at these elements in the ICM-like ESC sub-population. Both factors support cooperative recognition in these lineages, with GATA6 bound alongside SOX2 on a fraction of pluripotency enhancers and SOX2 alongside GATA6 more extensively on endoderm enhancers, suggesting that cooperative binding between these antagonistic factors both supports self-renewal and prepares progenitor cells for later differentiation.
AB - In early mammalian development, cleavage stage blastomeres and inner cell mass (ICM) cells co-express embryonic and extra-embryonic transcriptional determinants. Using a protein-based double reporter we identify an embryonic stem cell (ESC) population that co-expresses the extra-embryonic factor GATA6 alongside the embryonic factor SOX2. Based on single cell transcriptomics, we find this population resembles the unsegregated ICM, exhibiting enhanced differentiation potential for endoderm while maintaining epiblast competence. To relate transcription factor binding in these cells to future fate, we describe a complete enhancer set in both ESCs and naive extra-embryonic endoderm stem cells and assess SOX2 and GATA6 binding at these elements in the ICM-like ESC sub-population. Both factors support cooperative recognition in these lineages, with GATA6 bound alongside SOX2 on a fraction of pluripotency enhancers and SOX2 alongside GATA6 more extensively on endoderm enhancers, suggesting that cooperative binding between these antagonistic factors both supports self-renewal and prepares progenitor cells for later differentiation.
KW - Blastocyst
KW - Cooperativity
KW - Embryonic Stem Cells
KW - Endoderm
KW - Enhancer
KW - Epiblast
KW - Lineage Priming
KW - nEnd
KW - Pluripotency
KW - Transcription
U2 - 10.1016/j.stemcr.2023.12.002
DO - 10.1016/j.stemcr.2023.12.002
M3 - Journal article
C2 - 38215757
AN - SCOPUS:85184607262
VL - 19
SP - 174
EP - 186
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 2
ER -
ID: 382985717