Extensive co-binding and rapid redistribution of NANOG and GATA6 during emergence of divergent lineages

Thompson, Joyce J.; Lee, Dong Hoon; Mitra, Apratim; Frail, Sarah; Dale, Ryan; Rocha, Pedro P.

doi:10.1038/s41467-022-31938-5

Cited by 26 publications

(33 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…al 2019). (Thompson et al 2022) with our SOX2-GATA6 cobound peaks in DP cells. D. Euler diagram projecting the NANOG-GATA6 cobound peaks from the in vivo data of the E3.5 blastocysts (Thompson et al 2022) with the SOX2-GATA6 cobound peaks in KOSR DP cells.…”

Section: Downstream Analysis Of Cutandrunsupporting

confidence: 67%

“…B. Euler diagram of SOX2 and GATA6 peaks in KOSR DP cells. C. Euler diagram showing the overlap of the GATA6-FLAG ChIP with NANOG reChIP ( Thompson et al 2022 ) with our SOX2-GATA6 cobound peaks in DP cells. D. Euler diagram projecting the NANOG-GATA6 cobound peaks from the in vivo data of the E3.5 blastocysts ( Thompson et al 2022 ) with the SOX2-GATA6 cobound peaks in KOSR DP cells.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation

Brickman

Riveiro

Al-Mousawi

et al. 2023

Preprint

View full text Add to dashboard Cite

In early mammalian development, cleavage stage blastomeres and cells of the inner cell mass (ICM) of the blastocyst co-express embryonic and extra-embryonic transcriptional determinants. Using a double protein-based reporter we identify embryonic stem cells (ESC) that co-express the extra-embryonic factor GATA6 alongside the embryonic factor SOX2 in specific conditions. Based on single cell transcriptomics we find these population resemble unsegregated ICM, exhibiting enhanced differentiation potential for endoderm while maintaining epiblast competence and suggesting they represent an ideal model to determine how GATA6 and SOX2 influence each other's DNA binding. To relate this binding to future fate, we describe a complete enhancer set in both ESCs and naive extraembryonic endoderm stem cells and ask whether SOX2 and GATA6 recognize these elements in 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. Our findings suggest that cooperative binding between these antagonistic factors both supports self-renewal and prepares progenitor cells for later differentiation.

show abstract

Section: Downstream Analysis Of Cutandrunsupporting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation

Brickman

Riveiro

Al-Mousawi

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Such enhancer reorganization by pioneer factors, including silencing of the starting cell's enhancers, has been proposed for iPSCs, where early and preferential binding to active somatic enhancers causes the redistribution of associated somatic transcription factors like P300 and the recruitment of enhancer silencing factors like Hdac1 13 . In addition, as we observed for Hnf4a and Rxra, pioneer factors can compete for binding sites in enhancers to influence lineage trajectories 48,49 .…”

Section: Discussionmentioning

confidence: 55%

Physiological reprogrammingin vivomediated by Sox4 pioneer factor activity

Katsuda

Sussman

Ito

et al. 2023

Preprint

View full text Add to dashboard Cite

Tissue damage elicits cell fate switching through a process called metaplasia, but how the starting cell fate is silenced and the new cell fate is activated has not been investigated in animals. In cell culture, pioneer transcription factors mediate ″reprogramming″ by opening new chromatin sites for expression that can attract transcription factors from the starting cell′s enhancers. Here we report that Sox4 is sufficient to initiate hepatobiliary metaplasia in the adult liver. In lineage-traced cells, we assessed the timing of Sox4-mediated opening of enhancer chromatin versus enhancer decommissioning. Initially, Sox4 directly binds to and closes hepatocyte regulatory sequences via a motif it overlaps with Hnf4a, a hepatocyte master regulator. Subsequently, Sox4 exerts pioneer factor activity to open biliary regulatory sequences. The results delineate a hierarchy by which gene networks become reprogrammed under physiological conditions, providing deeper insight into the basis for cell fate transitions in animals.

show abstract

“…Recent discoveries propose a role of pluripotency genes in participating the transition fom pluripotency to committed lineages by co-binding to lineage factors that redirect their binding to new enhancer sites, leading to regulatory interference from other factors inhibiting them to activate downstream targets, and eventually a gradual repression of the pluropotency gene transcription 21,33,34 . We show a comcomitant gradual loss of the pluripotency signature and increase in fate commitment during the ectodermal patterning process, suggesting possible involvement of similar epigenetic changes.…”

Section: Discussionmentioning

confidence: 99%

Maintenance of pluripotency in the entire ectoderm enables neural crest formation

Pajanoja¹,

Hsin²,

Olinger³

et al. 2023

Preprint

View full text Add to dashboard Cite

The ability of the pluripotent epiblast to contribute progeny to all three germ layers is thought to be lost after gastrulation. The later-forming neural crest (NC) rises from ectoderm and it remains poorly understood how its exceptionally high stem-cell potential to generate mesodermal- and endodermal-like cells is obtained. We monitored transcriptional changes from gastrulation to neurulation using single-cell-Multiplex-Spatial-Transcriptomics (scMST) complemented with RNA-sequencing. Unexpectedly, we find maintenance of undecided Nanog/Oct4-PouV/Klf4-positive pluripotent-like pan-ectodermal stem-cells spanning the entire ectoderm late in the neurulation process with ectodermal patterning completed only at the end of neurulation when pluripotency becomes restricted to NC, challenging our understanding of gastrulation. Furthermore, broad ectodermal pluripotency is found at all axial levels unrelated to the NC lineage the cells later commit to, suggesting a general role in stemness enhancement and proposing a mechanism by which the NC acquires its ability to form derivatives beyond “ectodermal-capacity” in chick and mouse embryos.

show abstract

Extensive co-binding and rapid redistribution of NANOG and GATA6 during emergence of divergent lineages

Cited by 26 publications

References 101 publications

Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation

Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation

Physiological reprogrammingin vivomediated by Sox4 pioneer factor activity

Maintenance of pluripotency in the entire ectoderm enables neural crest formation

Contact Info

Product

Resources

About