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254 results on '"Brickman, Joshua M."'

1. Differential elasticity in lineage segregation of embryonic stem cells

Author

Ritter, Christine M., Leijnse, Natascha, Barooji, Younes Farhangi, Brickman, Joshua M., Doostmohammadi, Amin, and Oddershede, Lene B.

Subjects
Physics - Biological Physics, Condensed Matter - Soft Condensed Matter, Quantitative Biology - Cell Behavior
Abstract

The question of what guides lineage segregation is central to development, where cellular differentiation leads to segregated cell populations destined for specialized functions. Here, using optical tweezers measurements of mouse embryonic stem cells (mESCs), we reveal a mechanical mechanism based on differential elasticity in the second lineage segregation of the embryonic inner cell mass into epiblast (EPI) cells - that will develop into the fetus - and primitive endoderm (PrE) - which will form extraembryonic structures such as the yolk sac. Remarkably, we find that these mechanical differences already occur during priming and not just after a cell has committed to differentiation. Specifically, we show that the mESCs are highly elastic compared to any other reported cell type and that the PrE cells are significantly more elastic than EPI-primed cells. Using a model of two cell types differing only in elasticity we show that differential elasticity alone can lead to segregation between cell types, suggesting that the mechanical attributes of the cells contribute to the segregation process. Our findings present differential elasticity as a previously unknown mechanical contributor to the lineage segregation during the embryo morphogenesis.

Published
2022

10. Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst

Author

Simon, Claire S., primary, McCarthy, Afshan, additional, Woods, Laura, additional, Staneva, Desislava, additional, Huang, Qiulin, additional, Linneberg-Agerholm, Madeleine, additional, Faulkner, Alex, additional, Papathanasiou, Athanasios, additional, Elder, Kay, additional, Snell, Phil, additional, Christie, Leila, additional, Garcia, Patricia, additional, Shaikly, Valerie, additional, Taranissi, Mohamed, additional, Choudhary, Meenakshi, additional, Herbert, Mary, additional, Brickman, Joshua M, additional, and Niakan, Kathy K., additional

Published
2024
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16. Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development

Author

Kim, Junil, primary, Rothová, Michaela Mrugala, additional, Madan, Esha, additional, Rhee, Siyeon, additional, Weng, Guangzheng, additional, Palma, António M., additional, Liao, Linbu, additional, David, Eyal, additional, Amit, Ido, additional, Hajkarim, Morteza Chalabi, additional, Vudatha, Vignesh, additional, Gutiérrez-García, Andrés, additional, Moreno, Eduardo, additional, Winn, Robert, additional, Trevino, Jose, additional, Fisher, Paul B., additional, Brickman, Joshua M., additional, Gogna, Rajan, additional, and Won, Kyoung Jae, additional

Published
2023
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19. Transcriptional heterogeneity and cell cycle regulation as central determinants of Primitive Endoderm priming

Author

Perera, Marta, Nissen, Silas Boye, Proks, Martin, Pozzi, Sara, Monteiro, Rita S., Trusina, Ala, and Brickman, Joshua M.

Subjects
EXPRESSION, Mouse, selection, PLURIPOTENCY, General Biochemistry, Genetics and Molecular Biology, EPIBLAST, CULTURE, Mice, Pregnancy, G1 PHASE, Animals, Cell Lineage, SEGREGATION, endoderm, Mammals, General Immunology and Microbiology, General Neuroscience, Endoderm, Gene Expression Regulation, Developmental, Cell Differentiation, Cell Cycle Checkpoints, differentiation, General Medicine, embryonic stem cells, Fibroblast Growth Factors, SELF-RENEWAL, Blastocyst, GROUND-STATE, embryonic structures, Female, cell cycle, heterogeneity, EMBRYONIC STEM-CELLS, Germ Layers
Abstract

During embryonic development cells acquire identity at the same time as they are proliferating, implying that an intrinsic facet of cell fate choice requires coupling lineage decisions to rates of cell division. How is the cell cycle regulated to promote or suppress heterogeneity and differentiation? We explore this question combining time lapse imaging with single cell RNA-seq in the contexts of self-renewal, priming and differentiation of embryonic stem cells (ESCs) towards the Primitive Endoderm lineage (PrE). Since ESCs are derived from the Inner Cell Mass of the mammalian blastocyst, ESCs in standard culture conditions are transcriptionally heterogeneous containing subfractions that are primed for either of the two ICM lineages, Epiblast and PrE. These subfractions represent dynamic states that can readily interconvert in culture, and the PrE subfraction is functionally primed for endoderm differentiation. Here we find that differential regulation of cell cycle can tip the balance between these primed populations, such that naïve ESC culture conditions promote Epiblast-like expansion and PrE differentiation stimulates the selective proliferation of PrE-primed cells. In endoderm differentiation, we find that this change is accompanied by a counter-intuitive increase in G1 length that also appears replicatedin vivo. While FGF/ERK signalling is a known key regulator of ESCs and PrE differentiation, we find it is not just responsible for ESCs heterogeneity, but also cell cycle synchronisation, required for the inheritance of similar cell cycles between sisters and cousins. Taken together, our results point to a tight relationship between transcriptional heterogeneity and cell cycle regulation in the context of lineage priming, with primed cell populations providing a pool of flexible cell types that can be expanded in a lineage-specific fashion while allowing plasticity during early determination.

Published
2022

23. Evolutionary Origin of Vertebrate OCT4/POU5 Functions in Supporting Pluripotency

Author

Sukparangsi, Woranop, primary, Morganti, Elena, additional, Lowndes, Molly, additional, Mayeur, Hélène, additional, Weisser, Melanie, additional, Hammachi, Fella, additional, Peradziryi, Hanna, additional, Roske, Fabian, additional, Hölzenspies, Jurriaan, additional, Livigni, Alessandra, additional, Godard, Benoit Gilbert, additional, Sugahara, Fumiaki, additional, Kuratani, Shigeru, additional, Montoya, Guillermo, additional, Frankenberg, Stephen R., additional, Mazan, Sylvie, additional, and Brickman, Joshua M, additional

Published
2022
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28. Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development.

Author

Junil Kim, Rothová, Michaela Mrugala, Madan, Esha, Rhee, Siyeon, Guangzheng Weng, Palma, António M., Liao, Linbu, David, Eyal, Amit, Ido, Hajkarim, Morteza Chalabi, Vudatha, Vignesh, Gutiérrez-García, Andrés, Moreno, Eduardo, Winn, Robert, Trevino, Jose, Fisher, Paul B., Brickman, Joshua M., Gogna, Rajan, and Kyoung Jae Won

Subjects
GENE expression, EMBRYOLOGY, CELL differentiation, GENETIC regulation, RNA sequencing
Abstract

Development of multicellular organisms is orchestrated by persistent cell–cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single-cell RNA-seq technology cannot adequately analyze cell–cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell–cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single-cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells upregulate Lhx5 and Nkx2-1 genes, when exclusively interacting with definitive endoderm (DE) cells. Moreover, there was a reciprocal impact on the transcriptome of DE cells, as they tend to upregulate Rax and Gsc when in contact with NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-t-distributed stochastic neighboring embedding to display the pseudospatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development

Author

Kim, Junil, primary, Rothová, Michaela Mrugala, additional, Madan, Esha, additional, Rhee, Siyeon, additional, Weng, Guangzheng, additional, Palma, António M., additional, Liao, Linbu, additional, David, Eyal, additional, Amit, Ido, additional, Hajkarim, Morteza Chalabi, additional, Gutiérrez-García, Andrés, additional, Fisher, Paul B., additional, Brickman, Joshua M., additional, Gogna, Rajan, additional, and Won, Kyoung Jae, additional

Published
2021
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39. Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release

Author

Narita, Takeo, primary, Ito, Shinsuke, additional, Higashijima, Yoshiki, additional, Chu, Wai Kit, additional, Neumann, Katrin, additional, Walter, Jonas, additional, Satpathy, Shankha, additional, Liebner, Tim, additional, Hamilton, William B., additional, Maskey, Elina, additional, Prus, Gabriela, additional, Shibata, Marika, additional, Iesmantavicius, Vytautas, additional, Brickman, Joshua M., additional, Anastassiadis, Konstantinos, additional, Koseki, Haruhiko, additional, and Choudhary, Chunaram, additional

Published
2021
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41. 2020_BSDB_2.pdf

Author

Hamilton, William, Brickman, Joshua M., Knudsen, Teresa E., Nielsen, Alexander Valentin, and Trusina, Ala

Subjects
embryonic structures
Abstract

Mouse embryonic stem cells (mESCs) represent are the primary in vitro model for many aspects of early embryonic development. They are the descendants of the cells of the cells inner cell mass (ICM) of early blastocyst and whilst they maintain the potency of their forerunner cells, they acquire the ability to self-renew during ex vivo culture.Over the past decades considerable work has focused in understanding the molecular basis of this ex vivo self-renewal and how it relates to cellular potency. The dominant model is that the combined activities of a discrete network of transcription factors (TFs), referred to as the pluripotency network, act cooperatively to maintain their own expression and promote proliferation whilst simultaneously blocking differentiation. However useful, this model has yet to adequately explain why such a complex, self-sustaining and robust self-renewal network would have evolved in a population that exhibits negligible self-renewal in vivo. In the context of Waddingtonian lineage transitions, as a cell traverses developmental landscapes, the gene regulatory network (GRN) that establishes each discernible cell state must also define the range of lineage trajectories available to it, incorporating various inputs like signalling and positional information to choose one trajectory over the other. Here we present data that argues that the canonical pluripotency network can be divided into at least two distinct subgroups; those that promote lineage and those that balance lineage decisions, with both classes of TFs functioning in creating a state of lineage competency, similar to what is seen in the ICM. Specifically, we see that the combined activities of ESRRB and NANOG promote a gene expression signature similar to the ICM when expressed at a near 1:1 ratio. However if ESRRB expression persists in the absence of NANOG it is no longer tethered to epiblast associated loci and acts to drive the expression of primitive endoderm (PrE) associated genes. We formalise the kinetics of this interaction and show that oscillation of ERK signalling result in asynchronous fluctuations in NANOG and ESRRB ratios and a concomitant stepwise increase in PrE determinants, similar to what is seen in the ICM. From this we propose that the ex vivo culture environment selects for ratios of TFs that, whilst maintaining the expression of ICM-like genes, and as such potency, prevent cells from progressing further in development.

Published
2020
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48. An HMG-like protein that can switch a transcriptional activator to a repressor

Author

Lehming, Norbert, Thanos, Dimitris, Brickman, Joshua M., Ma, Jun, Maniatls, Tom, and Ptashne, Mark

Subjects
Genetic transcription -- Regulation, Drosophila -- Observations, Proteins -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A Drosophila HMGI protein, DSP1, switches the transcriptional activators Dorsal and NF-KB to repressors. The switching mechanism involves a negative regulatory element that is present near the Dorsal-binding areas in the Zen enhancer and near the NF-KB-binding region in the human interferon-beta promoter. The HMG-like proteins help identify if a specific regulator serves as a transcriptional activator or repressor.

Published
1994

49. New eukaryotic transcriptional repressors

Author

Saha, Shamol, Brickman, Joshua M., Lehming, Norbert, and Ptashne, Mark

Subjects
Genetic transcription -- Regulation, Eukaryotic cells -- Genetic aspects, Genetic code -- Identification and classification, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

An Escherichia coli-encoded sequence attached to a DNA-binding fragment of GAL4 converts the latter into a highly basic repressor. A mutant derivative and a synthetic peptide prove as effective, and sometimes superior. Researchers frequently bind the same GAL4 fragment to other E. coli sequences to create activators. The new repressing regions seem to interact with and inhibit activating regions bound nearby on DNA.

Published
1993

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