Episodes
Episodes
Thursday Jun 23, 2022
Epigenetic Clocks and Biomarkers of Ageing (Morgan Levine)
Thursday Jun 23, 2022
Thursday Jun 23, 2022
In this episode of the Epigenetics Podcast, we caught up with Morgan Levine from Altos lab to talk about her work on Epigenetic Clocks and Biomarkers of Ageing.
The Levine Lab focuses on deciphering mechanisms that lead to epigenetic ageing, which can be measured by epigenetic clocks. Epigenetic clocks were first described in 2011 by Bocklandt et al.. Later-on, the Horvath and the Hannum clock were described by using a combination of CpGs to calculate biological/epigenetic age in contrast to chronological age.
The Levine Lab themselves worked on generating an advanced version of an Epigenetic clock, called "DNAm PhenoAge" that will now be used, and not only in human samples. The team now moves to mouse models and to cells in a dish and using those models to investigate the mechanisms behind epigenetic aging.
References
Liu, Z., Leung, D., Thrush, K., Zhao, W., Ratliff, S., Tanaka, T., Schmitz, L. L., Smith, J. A., Ferrucci, L., & Levine, M. E. (2020). Underlying features of epigenetic aging clocks in vivo and in vitro. Aging cell, 19(10), e13229. https://doi.org/10.1111/acel.13229
Levine, M. E., Lu, A. T., Quach, A., Chen, B. H., Assimes, T. L., Bandinelli, S., Hou, L., Baccarelli, A. A., Stewart, J. D., Li, Y., Whitsel, E. A., Wilson, J. G., Reiner, A. P., Aviv, A., Lohman, K., Liu, Y., Ferrucci, L., & Horvath, S. (2018). An epigenetic biomarker of aging for lifespan and healthspan. Aging, 10(4), 573–591. https://doi.org/10.18632/aging.101414
Levine, M., McDevitt, R. A., Meer, M., Perdue, K., Di Francesco, A., Meade, T., Farrell, C., Thrush, K., Wang, M., Dunn, C., Pellegrini, M., de Cabo, R., & Ferrucci, L. (2020). A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin. eLife, 9, e59201. https://doi.org/10.7554/eLife.59201
Kuo, C. L., Pilling, L. C., Atkins, J. C., Masoli, J., Delgado, J., Tignanelli, C., Kuchel, G., Melzer, D., Beckman, K. B., & Levine, M. (2020). COVID-19 severity is predicted by earlier evidence of accelerated aging. medRxiv : the preprint server for health sciences, 2020.07.10.20147777. https://doi.org/10.1101/2020.07.10.20147777
Related Episodes
Aging and Epigenetics (Peter Tessarz)
Epigenetic Mechanisms of Aging and Longevity (Shelley Berger)
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Thursday Jun 09, 2022
Epigenetic and Metabolic Regulation of Early Development (Jan Żylicz)
Thursday Jun 09, 2022
Thursday Jun 09, 2022
In this episode of the Epigenetics Podcast, we caught up with Jan Żylicz from the Novo Nordisk Foundation Center for Stem Cell Medicine to talk about his work on epigenetic and metabolic regulation of early development.
The focus of the Żylicz Lab is studying early development and how this process is influenced by epigenetic factors. In more detail, the Team focuses on the function of chromatin modifiers in this process. Primed pluripotent epiblasts in vivo show a distinct chromatin landscape that is characterized by high levels of histone H3 lysine 9 dimethylation (H3K9me2) and rearranged Polycomb-associated histone H3 lysine 27 trimethylation (H3K27me3) at thousands of genes along the genome. However, the function of only about 100 loci is impaired. The Żylicz Lab tries to understand this process behind and also the cause of this discrepancy.
References
Żylicz, J. J., Bousard, A., Žumer, K., Dossin, F., Mohammad, E., da Rocha, S. T., Schwalb, B., Syx, L., Dingli, F., Loew, D., Cramer, P., & Heard, E. (2019). The Implication of Early Chromatin Changes in X Chromosome Inactivation. Cell, 176(1–2), 182-197.e23. https://doi.org/10.1016/j.cell.2018.11.041
Dossin, F., Pinheiro, I., Żylicz, J. J., Roensch, J., Collombet, S., Le Saux, A., Chelmicki, T., Attia, M., Kapoor, V., Zhan, Y., Dingli, F., Loew, D., Mercher, T., Dekker, J., & Heard, E. (2020). SPEN integrates transcriptional and epigenetic control of X-inactivation. Nature, 578(7795), 455–460. https://doi.org/10.1038/s41586-020-1974-9
Related Episodes
Epigenetics and X-Inactivation (Edith Heard)
The Effects of Early Life Stress on Mammalian Development (Catherine J. Peña)
DNA Methylation and Mammalian Development (Déborah Bourc'his)
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Thursday May 26, 2022
Multiple challenges of CUT&Tag (Cassidee McDonough, Kyle Tanguay)
Thursday May 26, 2022
Thursday May 26, 2022
In this episode of the Epigenetics Podcast, we caught up with Active Motif scientists Casidee McDonough from Epigenetic Services and Kyle Tanguay from R&D to talk about technical details of the CUT&Tag protocol and current developments around this method in our R&D Team.
CUT&Tag, which is short for Cleavage Under Targets and Tagmentation, is a molecular biology method that is used to investigate interactions between proteins and DNA and to identify DNA binding sites for their protein of interest. Although CUT&Tag is similar in some ways to ChIP assays, the starting material for CUT&Tag is live, permeabilized cells or isolated cell nuclei, rather than cells or tissue that have been crosslinked with formaldehyde as is the case when performing ChIP. The CUT&Tag method is very sensitive and has been reported to work with as few as 60 cells for some histone modifications. The ability to work with such small numbers of cells is an advantage for researchers working on specific cell types, such as rare neuronal populations, pancreatic islets, or stem cells that are difficult to obtain in large numbers.
In this Episode we discuss the CUT&Tag workflow in detail, talk about the challenges and pitfalls, give guidelines on how to do a good CUT&Tag experiment and offer a glimpse into the future of CUT&Tag product development at Active Motif.
References
Comprehensive Guide to Understanding and Using CUT&Tag Assays
Library QC for ATAC-Seq and CUT&Tag | AKA “Does My Library Look Okay?”
Kaya-Okur, H.S., Wu, S.J., Codomo, C.A. et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat Commun 10, 1930 (2019). https://doi.org/10.1038/s41467-019-09982-5
Podcast: Chromatin Profiling: From ChIP to CUT&RUN, CUT&Tag and CUTAC (Steven Henikoff)
CUT&Tag-validated antibodies
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Thursday May 12, 2022
Thursday May 12, 2022
In this episode of the Epigenetics Podcast, we caught up with Ian Maze from Ichan School of Medicine at Mount Sinai and a Howard Hughes Medical Institute (HHMI) Investigator to talk about his work on the role of histone dopaminylation and serotinylation in neuronal plasticity.
The Maze group focuses on understanding the complex interplay between chromatin regulatory mechanisms in brain and neuronal plasticity. The lab places an emphasis on psychiatric disorders associated with monoaminergic (e.g., serotonin, dopamine, etc.) dysfunction, such as major depressive disorder and drug addiction. In particular the Maze team has investigated cocaine addiction and its effect on chromatin by serotonylation and dopaminylation of Histone H3 Tails.
References
Maze, I., Covington, H. E., Dietz, D. M., LaPlant, Q., Renthal, W., Russo, S. J., Mechanic, M., Mouzon, E., Neve, R. L., Haggarty, S. J., Ren, Y., Sampath, S. C., Hurd, Y. L., Greengard, P., Tarakhovsky, A., Schaefer, A., & Nestler, E. J. (2010). Essential Role of the Histone Methyltransferase G9a in Cocaine-Induced Plasticity. Science, 327(5962), 213–216. https://doi.org/10.1126/science.1179438
Farrelly, L. A., Thompson, R. E., Zhao, S., Lepack, A. E., Lyu, Y., Bhanu, N. V., Zhang, B., Loh, Y.-H. E., Ramakrishnan, A., Vadodaria, K. C., Heard, K. J., Erikson, G., Nakadai, T., Bastle, R. M., Lukasak, B. J., Zebroski, H., Alenina, N., Bader, M., Berton, O., … Maze, I. (2019). Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3. Nature, 567(7749), 535–539. https://doi.org/10.1038/s41586-019-1024-7
Lepack, A. E., Werner, C. T., Stewart, A. F., Fulton, S. L., Zhong, P., Farrelly, L. A., Smith, A. C. W., Ramakrishnan, A., Lyu, Y., Bastle, R. M., Martin, J. A., Mitra, S., O’Connor, R. M., Wang, Z.-J., Molina, H., Turecki, G., Shen, L., Yan, Z., Calipari, E. S., … Maze, I. (2020). Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking. Science, 368(6487), 197–201. https://doi.org/10.1126/science.aaw8806
Related Episodes
Development of Integrative Machine Learning Tools for Neurodegenerative Diseases (Enrico Glaab)
Epigenetic Influence on Memory Formation and Inheritance (Isabelle Mansuy)
CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird)
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Thursday Apr 28, 2022
The Role of Blimp-1 in Immune-Cell Differentiation (Erna Magnúsdóttir)
Thursday Apr 28, 2022
Thursday Apr 28, 2022
In this episode of the Epigenetics Podcast, we caught up with Erna Magnúsdóttir from the University of Iceland to talk about her work on the role of Blimp-1 in immune-cell differentiation.
The Magnúsdóttir Lab is interested in how the mammalian genome is interpreted in a context dependent manner, leading to different cellular states, by using mouse primordial germ cells as well as mouse and human B-cells as model systems. More specifically, the team is interested in the Transcription Factor Blimp-1 and its effect on immune cell differentiation. Next to its function in immune cells, Blimp-1 also plays a role in Waldenström’s macroglobulinemia. The lab hopes to reveal the intricacies in disease progression and alteration in cellular states to increasingly aggressive tumor behavior.
References
Magnúsdóttir, E., Dietmann, S., Murakami, K. et al. A tripartite transcription factor network regulates primordial germ cell specification in mice. Nat Cell Biol 15, 905–915 (2013). https://doi.org/10.1038/ncb2798
Anderson, K.J., Ósvaldsdóttir, Á.B., Atzinger, B. et al. The BLIMP1—EZH2 nexus in a non-Hodgkin lymphoma. Oncogene 39, 5138–5151 (2020). https://doi.org/10.1038/s41388-020-1347-8
Related Episodes
Pioneer Transcription Factors and Their Influence on Chromatin Structure (Ken Zaret)
DNA Methylation and Mammalian Development (Déborah Bourc'his)
The Role of SMCHD1 in Development and Disease (Marnie Blewitt)
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Thursday Apr 14, 2022
Thursday Apr 14, 2022
In this episode of the Epigenetics Podcast, we speak with Peter Smibert, Vice President of Biology at 10X Genomics to talk about an exciting new method in Multimodal Characterization of Cellular Identity using Barcoding.
During his time at the New York Genome Center, Peter Smibert was instrumental in the development of a new method called "Cellular Indexing of Transcriptomes and Epitopes by Sequencing" short CITE-Seq. This method enables the characterization of a cell's transcriptome, while at the same time, also allows the characterization of the cell's protein surface markers - at the single cell level. In CITE-Seq, sequencing adapters are coupled to antibodies that recognize surface proteins, which can then be detected by sequencing.
Further advancements of the CITE-Seq method led to the launch of BioLegend’s TOTAL-Seq and the integration of scATAC-Seq into the workflow. With the integration of scATAC-Seq in the CITE-Seq protocol, it is now possible to characterize single-cells along the path of the central dogma of biology, this is why the method called DOGMA-Seq.
References
https://cite-seq.com
Baron, M., Yanai, I. New skin for the old RNA-Seq ceremony: the age of single-cell multi-omics. Genome Biol 18, 159 (2017). https://doi.org/10.1186/s13059-017-1300-5
Stoeckius, M., Zheng, S., Houck-Loomis, B. et al. Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics. Genome Biol 19, 224 (2018). https://doi.org/10.1186/s13059-018-1603-1
Stoeckius, M., Hafemeister, C., Stephenson, W. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat Methods 14, 865–868 (2017). https://doi.org/10.1038/nmeth.4380
Mimitou, E.P., Cheng, A., Montalbano, A. et al. Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells. Nat Methods 16, 409–412 (2019). https://doi.org/10.1038/s41592-019-0392-0
Related Episodes
Epigenome-based Precision Medicine (Eleni Tomazou)
ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells
Investigating the Dynamics of Epigenetic Plasticity in Cancer with Single Cell Technologies (Céline Vallot)
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Thursday Mar 31, 2022
Thursday Mar 31, 2022
In this episode of the Epigenetics Podcast, we caught up with Sara Wickström, Director at the Max Planck Institute for Molecular Biomedicine in Münster, to talk about her work on the effect of mechanotransduction on chromatin structure and transcription in stem cells.
Sara Wickström and her team focus on the stem cell niche and how that niche affects stem cell function. In order to study the native niche and to even be able to manipulate it, the Wickström Lab was able to develop a ex vivo culture system, allowing systematic identification of factors driving stem cell dynamics and plasticity.
Stem cells in the stem cell niche are exposed to external stimuli such as physical forces which control their growth, fate and self renewal. Recent work in the Wickström lab showed how mechanical signals influence transcriptional regulation, chromatin organization, and nuclear architecture and how this affects aging or lineage commitment. In this Episode we also discuss how chromatin can act as a sensor of mechanical signals taking advantage of the different physical properties of eu- and heterochromatin.
References
Le, H. Q., Ghatak, S., Yeung, C. Y., Tellkamp, F., Günschmann, C., Dieterich, C., Yeroslaviz, A., Habermann, B., Pombo, A., Niessen, C. M., & Wickström, S. A. (2016). Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. Nature cell biology, 18(8), 864–875. https://doi.org/10.1038/ncb3387
Nava, M. M., Miroshnikova, Y. A., Biggs, L. C., Whitefield, D. B., Metge, F., Boucas, J., Vihinen, H., Jokitalo, E., Li, X., García Arcos, J. M., Hoffmann, B., Merkel, R., Niessen, C. M., Dahl, K. N., & Wickström, S. A. (2020). Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage. Cell, 181(4), 800–817.e22. https://doi.org/10.1016/j.cell.2020.03.052
Koester, J., Miroshnikova, Y. A., Ghatak, S., Chacón-Martínez, C. A., Morgner, J., Li, X., Atanassov, I., Altmüller, J., Birk, D. E., Koch, M., Bloch, W., Bartusel, M., Niessen, C. M., Rada-Iglesias, A., & Wickström, S. A. (2021). Niche stiffening compromises hair follicle stem cell potential during ageing by reducing bivalent promoter accessibility. Nature cell biology, 23(7), 771–781. https://doi.org/10.1038/s41556-021-00705-x
Maki, K., Nava, M. M., Villeneuve, C., Chang, M., Furukawa, K. S., Ushida, T., & Wickström, S. A. (2021). Hydrostatic pressure prevents chondrocyte differentiation through heterochromatin remodeling. Journal of cell science, 134(2), jcs247643. https://doi.org/10.1242/jcs.247643
Related Episodes
Nutriepigenetics: The Effects of Diet on Behavior (Monica Dus)
Epigenetic Regulation of Stem Cell Self-Renewal and Differentiation (Peggy Goodell)
The Effect of Vitamin D on the Epigenome (Folami Ideraabdullah)
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Wednesday Mar 16, 2022
Single-Cell Technologies using Microfluidics (Ben Hindson, CSO of 10x Genomics)
Wednesday Mar 16, 2022
Wednesday Mar 16, 2022
In this episode of the Epigenetics Podcast, we caught up with Ben Hindson, Chief Scientific Officer at 10X Genomics, to talk about single-cell technologies using microfluidics.
Epigenetics has moved well past a simple understanding of a single epigenetic layer of control at genomic regions of interest, thanks to advances in many techniques and the application of “multiomics”. We can now analyze genome-wide histone modification patterns, transcription factor binding profiles, chromatin accessibility profiles, three-dimensional chromosomal conformation, and DNA methylation dynamics combined with transcriptomic analyses and associated analytical platforms.
Bulk Assays, like ATAC-Seq or ChIP, despite all their advantages, do not provide information about the chromatin states of individual subpopulations of cells within a sample. To identify chromatin features in heterogeneous populations, such as blood, pancreas, and brain, those analysis need to be performed at a single-cell level. 10X Genomics has been at the forefront of the movement into the single cell space and in this Episode we discuss this work with Ben Hindson, CSO of 10X genomics.
References
https://www.10xgenomics.com/products/single-cell-multiome-atac-plus-gene-expression
Spectrum of Innovation
Multiomic Epigenetic Analysis Turns Short Stories into Epic Tales
Single-Cell Multiome Service
Related Episodes
Epigenome-based Precision Medicine (Eleni Tomazou)
ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells
Investigating the Dynamics of Epigenetic Plasticity in Cancer with Single Cell Technologies (Céline Vallot)
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Email: podcast@activemotif.com