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Article ; Online: The transcription factor code in iPSC reprogramming.

Deng, Weixian / Jacobson, Elsie C / Collier, Amanda J / Plath, Kathrin

Current opinion in genetics & development

2021 Volume 70, Page(s) 89–96

Abstract: Transcription factor (TF)-induced reprogramming of somatic cells across lineages and to induced pluripotent stem cells (iPSCs) has revealed a remarkable plasticity of differentiated cells and presents great opportunities for generating clinically ... ...

Abstract	Transcription factor (TF)-induced reprogramming of somatic cells across lineages and to induced pluripotent stem cells (iPSCs) has revealed a remarkable plasticity of differentiated cells and presents great opportunities for generating clinically relevant cell types for disease modeling and regenerative medicine. The understanding of iPSC reprogramming provides insights into the mechanisms that safeguard somatic cell identity, drive epigenetic reprogramming, and underlie cell fate specification in vivo. The combinatorial action of TFs has emerged as the key mechanism for the direct and indirect effects of reprogramming factors that induce the remodelling of the enhancer landscape. The interplay of TFs in iPSC reprogramming also yields trophectoderm- and extraembryonic endoderm-like cell populations, uncovering an intriguing plasticity of cell states and opening new avenues for exploring cell fate decisions during early embryogenesis.
MeSH term(s)	Animals ; Cellular Reprogramming ; Embryonic Development ; Epigenesis, Genetic ; Humans ; Induced Pluripotent Stem Cells/chemistry ; Induced Pluripotent Stem Cells/metabolism ; Transcription Factors/metabolism
Chemical Substances	Transcription Factors
Language	English
Publishing date	2021-07-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1077312-5
ISSN	1879-0380 ; 0959-437X
ISSN (online)	1879-0380
ISSN	0959-437X
DOI	10.1016/j.gde.2021.06.003
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Article: Identifying Human Naïve Pluripotent Stem Cells − Evaluating State‐Specific Reporter Lines and Cell‐Surface Markers

Collier, Amanda J / Peter J. Rugg‐Gunn

BioEssays. 2018 May, v. 40, no. 5

2018

Abstract: Recent reports that human pluripotent stem cells can be captured in a spectrum of states with variable properties has prompted a re‐evaluation of how pluripotency is acquired and stabilised. The latest additions to the stem cell hierarchy open up ... ...

Abstract	Recent reports that human pluripotent stem cells can be captured in a spectrum of states with variable properties has prompted a re‐evaluation of how pluripotency is acquired and stabilised. The latest additions to the stem cell hierarchy open up opportunities for understanding human development, reprogramming, and cell state transitions more generally. Many of the new cell lines have been collectively termed ‘naïve’ human pluripotent stem cells to distinguish them from the conventional ‘primed’ cells. Here, several transcriptional and epigenetic hallmarks of human pluripotent states in the recently described cell lines are reviewed and evaluated. Methods to derive and identify human naïve pluripotent stem cells are also discussed, with a focus on the uses and future developments of state‐specific reporter cell lines and cell‐surface proteins. Finally, opportunities and uncertainties in naïve stem cell biology are highlighted, and the current limitations of human naïve pluripotent stem cells considered, particularly in the context of differentiation.
Keywords	cell lines ; epigenetics ; human development ; humans ; proteins ; stem cells ; transcription (genetics) ; uncertainty
Language	English
Dates of publication	2018-05
Size	p. e1700239.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.201700239
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Article ; Online: Identifying Human Naïve Pluripotent Stem Cells - Evaluating State-Specific Reporter Lines and Cell-Surface Markers.

Collier, Amanda J / Rugg-Gunn, Peter J

BioEssays : news and reviews in molecular, cellular and developmental biology

2018 Volume 40, Issue 5, Page(s) e1700239

Abstract: Recent reports that human pluripotent stem cells can be captured in a spectrum of states with variable properties has prompted a re-evaluation of how pluripotency is acquired and stabilised. The latest additions to the stem cell hierarchy open up ... ...

Abstract	Recent reports that human pluripotent stem cells can be captured in a spectrum of states with variable properties has prompted a re-evaluation of how pluripotency is acquired and stabilised. The latest additions to the stem cell hierarchy open up opportunities for understanding human development, reprogramming, and cell state transitions more generally. Many of the new cell lines have been collectively termed 'naïve' human pluripotent stem cells to distinguish them from the conventional 'primed' cells. Here, several transcriptional and epigenetic hallmarks of human pluripotent states in the recently described cell lines are reviewed and evaluated. Methods to derive and identify human naïve pluripotent stem cells are also discussed, with a focus on the uses and future developments of state-specific reporter cell lines and cell-surface proteins. Finally, opportunities and uncertainties in naïve stem cell biology are highlighted, and the current limitations of human naïve pluripotent stem cells considered, particularly in the context of differentiation.
MeSH term(s)	Cell Differentiation/genetics ; Cell Differentiation/physiology ; Cell Line ; Cellular Reprogramming/genetics ; Cellular Reprogramming/physiology ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Epigenomics ; Humans ; Pluripotent Stem Cells/metabolism
Language	English
Publishing date	2018-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.201700239
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Article ; Online: XIST directly regulates X-linked and autosomal genes in naive human pluripotent cells.

Dror, Iris / Chitiashvili, Tsotne / Tan, Shawn Y X / Cano, Clara T / Sahakyan, Anna / Markaki, Yolanda / Chronis, Constantinos / Collier, Amanda J / Deng, Weixian / Liang, Guohao / Sun, Yu / Afasizheva, Anna / Miller, Jarrett / Xiao, Wen / Black, Douglas L / Ding, Fangyuan / Plath, Kathrin

Cell

2024 Volume 187, Issue 1, Page(s) 110–129.e31

Abstract: X chromosome inactivation (XCI) serves as a paradigm for RNA-mediated regulation of gene expression, wherein the long non-coding RNA XIST spreads across the X chromosome in cis to mediate gene silencing chromosome-wide. In female naive human pluripotent ... ...

Abstract	X chromosome inactivation (XCI) serves as a paradigm for RNA-mediated regulation of gene expression, wherein the long non-coding RNA XIST spreads across the X chromosome in cis to mediate gene silencing chromosome-wide. In female naive human pluripotent stem cells (hPSCs), XIST is in a dispersed configuration, and XCI does not occur, raising questions about XIST's function. We found that XIST spreads across the X chromosome and induces dampening of X-linked gene expression in naive hPSCs. Surprisingly, XIST also targets specific autosomal regions, where it induces repressive chromatin changes and gene expression dampening. Thereby, XIST equalizes X-linked gene dosage between male and female cells while inducing differences in autosomes. The dispersed Xist configuration and autosomal localization also occur transiently during XCI initiation in mouse PSCs. Together, our study identifies XIST as the regulator of X chromosome dampening, uncovers an evolutionarily conserved trans-acting role of XIST/Xist, and reveals a correlation between XIST/Xist dispersal and autosomal targeting.
MeSH term(s)	Animals ; Female ; Humans ; Male ; Mice ; Gene Silencing ; Genes, X-Linked ; RNA, Long Noncoding/genetics ; X Chromosome/genetics ; Pluripotent Stem Cells/metabolism
Chemical Substances	RNA, Long Noncoding
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2023.11.033
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Species-specific regulation of XIST by the JPX/FTX orthologs.

Rosspopoff, Olga / Cazottes, Emmanuel / Huret, Christophe / Loda, Agnese / Collier, Amanda J / Casanova, Miguel / Rugg-Gunn, Peter J / Heard, Edith / Ouimette, Jean-François / Rougeulle, Claire

Nucleic acids research

2023 Volume 51, Issue 5, Page(s) 2177–2194

Abstract: X chromosome inactivation (XCI) is an essential process, yet it initiates with remarkable diversity in various mammalian species. XIST, the main trigger of XCI, is controlled in the mouse by an interplay of lncRNA genes (LRGs), some of which evolved ... ...

Abstract	X chromosome inactivation (XCI) is an essential process, yet it initiates with remarkable diversity in various mammalian species. XIST, the main trigger of XCI, is controlled in the mouse by an interplay of lncRNA genes (LRGs), some of which evolved concomitantly to XIST and have orthologues across all placental mammals. Here, we addressed the functional conservation of human orthologues of two such LRGs, FTX and JPX. By combining analysis of single-cell RNA-seq data from early human embryogenesis with various functional assays in matched human and mouse pluripotent stem- or differentiated post-XCI cells, we demonstrate major functional differences for these orthologues between species, independently of primary sequence conservation. While the function of FTX is not conserved in humans, JPX stands as a major regulator of XIST expression in both species. However, we show that different entities of JPX control the production of XIST at various steps depending on the species. Altogether, our study highlights the functional versatility of LRGs across evolution, and reveals that functional conservation of orthologous LRGs may involve diversified mechanisms of action. These findings represent a striking example of how the evolvability of LRGs can provide adaptative flexibility to constrained gene regulatory networks.
MeSH term(s)	Pregnancy ; Humans ; Female ; Mice ; Animals ; Placenta/metabolism ; X Chromosome Inactivation/genetics ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Mammals/genetics ; Embryo, Mammalian/metabolism
Chemical Substances	RNA, Long Noncoding
Language	English
Publishing date	2023-02-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkad029
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Article ; Online: Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states.

Chovanec, Peter / Collier, Amanda J / Krueger, Christel / Várnai, Csilla / Semprich, Claudia I / Schoenfelder, Stefan / Corcoran, Anne E / Rugg-Gunn, Peter J

Nature communications

2021 Volume 12, Issue 1, Page(s) 2098

Abstract: The transition from naive to primed pluripotency is accompanied by an extensive reorganisation of transcriptional and epigenetic programmes. However, the role of transcriptional enhancers and three-dimensional chromatin organisation in coordinating these ...

Abstract	The transition from naive to primed pluripotency is accompanied by an extensive reorganisation of transcriptional and epigenetic programmes. However, the role of transcriptional enhancers and three-dimensional chromatin organisation in coordinating these developmental programmes remains incompletely understood. Here, we generate a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells, and develop a network-graph approach to examine the atlas at multiple spatial scales. We uncover highly connected promoter hubs that change substantially in interaction frequency and in transcriptional co-regulation between pluripotent states. Small hubs frequently merge to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. We identify widespread state-specific differences in enhancer activity and interactivity that correspond with an extensive reconfiguration of OCT4, SOX2 and NANOG binding and target gene expression. These findings provide multilayered insights into the chromatin-based gene regulatory control of human pluripotent states.
MeSH term(s)	Chromatin/metabolism ; DNA Methylation ; Enhancer Elements, Genetic ; Gene Expression Regulation ; Humans ; Nanog Homeobox Protein/genetics ; Nanog Homeobox Protein/metabolism ; Octamer Transcription Factor-3/genetics ; Octamer Transcription Factor-3/metabolism ; Pluripotent Stem Cells/metabolism ; Promoter Regions, Genetic ; SOXB1 Transcription Factors/genetics ; SOXB1 Transcription Factors/metabolism ; Transcription Factors/metabolism
Chemical Substances	Chromatin ; NANOG protein, human ; Nanog Homeobox Protein ; Octamer Transcription Factor-3 ; POU5F1 protein, human ; SOX2 protein, human ; SOXB1 Transcription Factors ; Transcription Factors
Language	English
Publishing date	2021-04-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-22201-4
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Article ; Online: Comparative Principles of DNA Methylation Reprogramming during Human and Mouse In Vitro Primordial Germ Cell Specification.

von Meyenn, Ferdinand / Berrens, Rebecca V / Andrews, Simon / Santos, Fátima / Collier, Amanda J / Krueger, Felix / Osorno, Rodrigo / Dean, Wendy / Rugg-Gunn, Peter J / Reik, Wolf

Developmental cell

2022 Volume 57, Issue 23, Page(s) 2669–2671

Language	English
Publishing date	2022-12-05
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2022.11.009
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Article ; Online: Cell-Surface Proteomics Identifies Differences in Signaling and Adhesion Protein Expression between Naive and Primed Human Pluripotent Stem Cells.

Wojdyla, Katarzyna / Collier, Amanda J / Fabian, Charlene / Nisi, Paola S / Biggins, Laura / Oxley, David / Rugg-Gunn, Peter J

Stem cell reports

2020 Volume 14, Issue 5, Page(s) 972–988

Abstract: Naive and primed human pluripotent stem cells (hPSC) provide valuable models to study cellular and molecular developmental processes. The lack of detailed information about cell-surface protein expression in these two pluripotent cell types prevents an ... ...

Abstract	Naive and primed human pluripotent stem cells (hPSC) provide valuable models to study cellular and molecular developmental processes. The lack of detailed information about cell-surface protein expression in these two pluripotent cell types prevents an understanding of how the cells communicate and interact with their microenvironments. Here, we used plasma membrane profiling to directly measure cell-surface protein expression in naive and primed hPSC. This unbiased approach quantified over 1,700 plasma membrane proteins, including those involved in cell adhesion, signaling, and cell interactions. Notably, multiple cytokine receptors upstream of JAK-STAT signaling were more abundant in naive hPSC. In addition, functional experiments showed that FOLR1 and SUSD2 proteins are highly expressed at the cell surface in naive hPSC but are not required to establish human naive pluripotency. This study provides a comprehensive stem cell proteomic resource that uncovers differences in signaling pathway activity and has identified new markers to define human pluripotent states.
MeSH term(s)	Cell Adhesion ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Cell Line ; Cell Membrane/metabolism ; Folate Receptor 1/genetics ; Folate Receptor 1/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Proteome/genetics ; Proteome/metabolism ; Receptors, Cytokine/genetics ; Receptors, Cytokine/metabolism ; Signal Transduction
Chemical Substances	Cell Adhesion Molecules ; FOLR1 protein, human ; Folate Receptor 1 ; Membrane Glycoproteins ; Proteome ; Receptors, Cytokine ; SUSD2 protein, human
Language	English
Publishing date	2020-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2020.03.017
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Article ; Online: Genome-wide screening identifies Polycomb repressive complex 1.3 as an essential regulator of human naïve pluripotent cell reprogramming.

Collier, Amanda J / Bendall, Adam / Fabian, Charlene / Malcolm, Andrew A / Tilgner, Katarzyna / Semprich, Claudia I / Wojdyla, Katarzyna / Nisi, Paola Serena / Kishore, Kamal / Roamio Franklin, Valar Nila / Mirshekar-Syahkal, Bahar / D'Santos, Clive / Plath, Kathrin / Yusa, Kosuke / Rugg-Gunn, Peter J

Science advances

2022 Volume 8, Issue 12, Page(s) eabk0013

Abstract: Uncovering the mechanisms that establish naïve pluripotency in humans is crucial for the future applications of pluripotent stem cells including the production of human blastoids. However, the regulatory pathways that control the establishment of naïve ... ...

Abstract	Uncovering the mechanisms that establish naïve pluripotency in humans is crucial for the future applications of pluripotent stem cells including the production of human blastoids. However, the regulatory pathways that control the establishment of naïve pluripotency by reprogramming are largely unknown. Here, we use genome-wide screening to identify essential regulators as well as major impediments of human primed to naïve pluripotent stem cell reprogramming. We discover that factors essential for cell state change do not typically undergo changes at the level of gene expression but rather are repurposed with new functions. Mechanistically, we establish that the variant Polycomb complex PRC1.3 and PRDM14 jointly repress developmental and gene regulatory factors to ensure naïve cell reprogramming. In addition, small-molecule inhibitors of reprogramming impediments improve naïve cell reprogramming beyond current methods. Collectively, this work defines the principles controlling the establishment of human naïve pluripotency and also provides new insights into mechanisms that destabilize and reconfigure cell identity during cell state transitions.
MeSH term(s)	Cell Differentiation ; Cellular Reprogramming ; Gene Expression Regulation ; Humans ; Pluripotent Stem Cells/cytology ; Polycomb Repressive Complex 1/metabolism
Chemical Substances	Polycomb Repressive Complex 1 (EC 2.3.2.27)
Language	English
Publishing date	2022-03-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abk0013
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Article ; Online: TGFβ signalling is required to maintain pluripotency of human naïve pluripotent stem cells.

Osnato, Anna / Brown, Stephanie / Krueger, Christel / Andrews, Simon / Collier, Amanda J / Nakanoh, Shota / Quiroga Londoño, Mariana / Wesley, Brandon T / Muraro, Daniele / Brumm, A Sophie / Niakan, Kathy K / Vallier, Ludovic / Ortmann, Daniel / Rugg-Gunn, Peter J

eLife

2021 Volume 10

Abstract: The signalling pathways that maintain primed human pluripotent stem cells (hPSCs) have been well characterised, revealing a critical role for TGFβ/Activin/Nodal signalling. In contrast, the signalling requirements of naive human pluripotency have not ... ...

Abstract	The signalling pathways that maintain primed human pluripotent stem cells (hPSCs) have been well characterised, revealing a critical role for TGFβ/Activin/Nodal signalling. In contrast, the signalling requirements of naive human pluripotency have not been fully established. Here, we demonstrate that TGFβ signalling is required to maintain naive hPSCs. The downstream effector proteins - SMAD2/3 - bind common sites in naive and primed hPSCs, including shared pluripotency genes. In naive hPSCs, SMAD2/3 additionally bind to active regulatory regions near to naive pluripotency genes. Inhibiting TGFβ signalling in naive hPSCs causes the downregulation of SMAD2/3-target genes and pluripotency exit. Single-cell analyses reveal that naive and primed hPSCs follow different transcriptional trajectories after inhibition of TGFβ signalling. Primed hPSCs differentiate into neuroectoderm cells, whereas naive hPSCs transition into trophectoderm. These results establish that there is a continuum for TGFβ pathway function in human pluripotency spanning a developmental window from naive to primed states.
MeSH term(s)	Cell Differentiation/physiology ; Cell Line ; Cellular Reprogramming ; Humans ; Pluripotent Stem Cells/physiology ; Signal Transduction/physiology ; Smad2 Protein/genetics ; Smad2 Protein/metabolism ; Smad3 Protein/genetics ; Smad3 Protein/metabolism ; Transforming Growth Factor beta/genetics ; Transforming Growth Factor beta/metabolism
Chemical Substances	SMAD2 protein, human ; SMAD3 protein, human ; Smad2 Protein ; Smad3 Protein ; Transforming Growth Factor beta
Language	English
Publishing date	2021-08-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.67259
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