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

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2024 Jan 12

PMID 38215757

Authors

Alba Redo-Riveiro

Jasmina Al-Mousawi

Madeleine Linneberg-Agerholm

Martin Proks

Marta Perera

Nazmus Salehin

Joshua M Brickman

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Deep learning-based models for preimplantation mouse and human embryos based on single-cell RNA sequencing.

Proks M, Salehin N, Brickman J Nat Methods. 2024; 22(1):207-216.

PMID: 39543284 PMC: 11725497. DOI: 10.1038/s41592-024-02511-3.

Unraveling the mysteries of early embryonic arrest: genetic factors and molecular mechanisms.

Zhang J, Lv J, Qin J, Zhang M, He X, Ma B J Assist Reprod Genet. 2024; 41(12):3301-3316.

PMID: 39325344 PMC: 11706821. DOI: 10.1007/s10815-024-03259-7.

The primitive endoderm supports lineage plasticity to enable regulative development.

Linneberg-Agerholm M, Sell A, Redo-Riveiro A, Perera M, Proks M, Knudsen T Cell. 2024; 187(15):4010-4029.e16.

PMID: 38917790 PMC: 11290322. DOI: 10.1016/j.cell.2024.05.051.

Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously.

Guo M, Wu J, Chen C, Wang X, Gong A, Guan W Nat Commun. 2024; 15(1):668.

PMID: 38253551 PMC: 10803796. DOI: 10.1038/s41467-024-44969-x.

References

Ramirez F, Ryan D, Gruning B, Bhardwaj V, Kilpert F, Richter A . deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 2016; 44(W1):W160-5. PMC: 4987876. DOI: 10.1093/nar/gkw257. View

Anderson K, Hamilton W, Roske F, Azad A, Knudsen T, Canham M . Insulin fine-tunes self-renewal pathways governing naive pluripotency and extra-embryonic endoderm. Nat Cell Biol. 2017; 19(10):1164-1177. DOI: 10.1038/ncb3617. View

Morgani S, Brickman J . LIF supports primitive endoderm expansion during pre-implantation development. Development. 2015; 142(20):3488-99. DOI: 10.1242/dev.125021. View

White M, Angiolini J, Alvarez Y, Kaur G, Zhao Z, Mocskos E . Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo. Cell. 2016; 165(1):75-87. DOI: 10.1016/j.cell.2016.02.032. View

Knudsen T, Hamilton W, Proks M, Lykkegaard M, Linneberg-Agerholm M, Nielsen A . A bipartite function of ESRRB can integrate signaling over time to balance self-renewal and differentiation. Cell Syst. 2023; 14(9):788-805.e8. DOI: 10.1016/j.cels.2023.07.008. View

Li M, Izpisua Belmonte J . Ground rules of the pluripotency gene regulatory network. Nat Rev Genet. 2017; 18(3):180-191. DOI: 10.1038/nrg.2016.156. View

Yang J, Ryan D, Wang W, Tsang J, Lan G, Masaki H . Establishment of mouse expanded potential stem cells. Nature. 2017; 550(7676):393-397. PMC: 5890884. DOI: 10.1038/nature24052. View

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

Riveiro A, Brickman J . From pluripotency to totipotency: an experimentalist's guide to cellular potency. Development. 2020; 147(16). DOI: 10.1242/dev.189845. View

10.

Canham M, Sharov A, Ko M, Brickman J . Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript. PLoS Biol. 2010; 8(5):e1000379. PMC: 2876051. DOI: 10.1371/journal.pbio.1000379. View

11.

Garcia-Gonzalo F, Izpisua Belmonte J . Albumin-associated lipids regulate human embryonic stem cell self-renewal. PLoS One. 2008; 3(1):e1384. PMC: 2148252. DOI: 10.1371/journal.pone.0001384. View

12.

Skene P, Henikoff J, Henikoff S . Targeted in situ genome-wide profiling with high efficiency for low cell numbers. Nat Protoc. 2018; 13(5):1006-1019. DOI: 10.1038/nprot.2018.015. View

13.

Skene P, Henikoff S . An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. Elife. 2017; 6. PMC: 5310842. DOI: 10.7554/eLife.21856. View

14.

Nowotschin S, Setty M, Kuo Y, Liu V, Garg V, Sharma R . The emergent landscape of the mouse gut endoderm at single-cell resolution. Nature. 2019; 569(7756):361-367. PMC: 6724221. DOI: 10.1038/s41586-019-1127-1. View

15.

Boroviak T, Stirparo G, Dietmann S, Hernando-Herraez I, Mohammed H, Reik W . Single cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development. Development. 2018; 145(21). PMC: 6240320. DOI: 10.1242/dev.167833. View

16.

Meers M, Tenenbaum D, Henikoff S . Peak calling by Sparse Enrichment Analysis for CUT&RUN chromatin profiling. Epigenetics Chromatin. 2019; 12(1):42. PMC: 6624997. DOI: 10.1186/s13072-019-0287-4. View

17.

Calo E, Wysocka J . Modification of enhancer chromatin: what, how, and why?. Mol Cell. 2013; 49(5):825-37. PMC: 3857148. DOI: 10.1016/j.molcel.2013.01.038. View

18.

Hu M, Krause D, Greaves M, Sharkis S, Dexter M, Heyworth C . Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev. 1997; 11(6):774-85. DOI: 10.1101/gad.11.6.774. View

19.

Hamilton W, Mosesson Y, Monteiro R, Emdal K, Knudsen T, Francavilla C . Dynamic lineage priming is driven via direct enhancer regulation by ERK. Nature. 2019; 575(7782):355-360. DOI: 10.1038/s41586-019-1732-z. View

20.

Graf T, Enver T . Forcing cells to change lineages. Nature. 2009; 462(7273):587-94. DOI: 10.1038/nature08533. View