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8. Immune-privileged tissues formed from immunologically cloaked mouse embryonic stem cells survive long term in allogeneic hosts

Author

Harding, Jeffrey, primary, Vintersten-Nagy, Kristina, additional, Yang, Huijuan, additional, Tang, Jean Kit, additional, Shutova, Maria, additional, Jong, Eric D., additional, Lee, Ju Hee, additional, Massumi, Mohammad, additional, Oussenko, Tatiana, additional, Izadifar, Zohreh, additional, Zhang, Puzheng, additional, Rogers, Ian M., additional, Wheeler, Michael B., additional, Lye, Stephen J., additional, Sung, Hoon-Ki, additional, Li, ChengJin, additional, Izadifar, Mohammad, additional, and Nagy, Andras, additional

Published
2023
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11. AML cells have low spare reserve capacity in their respiratory chain that renders them susceptible to oxidative metabolic stress

Author

Sriskanthadevan, Shrivani, Jeyaraju, Danny V., Chung, Timothy E., Prabha, Swayam, Xu, Wei, Skrtic, Marko, Jhas, Bozhena, Hurren, Rose, Gronda, Marcela, Wang, Xiaoming, Jitkova, Yulia, Sukhai, Mahadeo A., Lin, Feng-Hsu, Maclean, Neil, Laister, Rob, Goard, Carolyn A., Mullen, Peter J., Xie, Stephanie, Penn, Linda Z., Rogers, Ian M., Dick, John E., Minden, Mark D., and Schimmer, Aaron D.

Published
2015
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15. Genome-wide characterization of the routes to pluripotency

Author

Hussein, Samer M.I., Puri, Mira C., Tonge, Peter D., Benevento, Marco, Corso, Andrew J., Clancy, Jennifer L., Mosbergen, Rowland, Li, Mira, Lee, Dong-Sung, Cloonan, Nicole, Wood, David L.A., Munoz, Javier, Middleton, Robert, Korn, Othmar, Patel, Hardip R., White, Carl A., Shin, Jong-Yeon, Gauthier, Maely E., Cao, Kim-Anh Le, Mar, Jessica C., Shakiba, Nika, Ritchie, William, Rasko, John E.J., Grimmond, Sean M., Zandstra, Peter W., Wells, Christine A., Preiss, Thomas, Seo, Jeong-Sun, Heck, Albert J.R., Rogers, Ian M., and Nagy, Andras

Subjects
Physiological aspects, Stem cell research, Somatic cells -- Physiological aspects
Abstract

Forced expression of four transcription factors--Oct4 (also called Pou5f1), Sox2, Klf4 and Myc (OSKM) (1)--induces molecular changes in somatic cells, which lead to pluripotency. The exogenous expression of these transcription [...], Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and -independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org.

Published
2014
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16. Divergent reprogramming routes lead to alternative stem-cell states

Author

Tonge, Peter D., Corso, Andrew J., Monetti, Claudio, Hussein, Samer M.I., Puri, Mira C., Michael, Iacovos P., Li, Mira, Lee, Dong-Sung, Mar, Jessica C., Cloonan, Nicole, Wood, David L., Gauthier, Maely E., Korn, Othmar, Clancy, Jennifer L., Preiss, Thomas, Grimmond, Sean M., Shin, Jong-Yeon, Seo, Jeong-Sun, Wells, Christine A., Rogers, Ian M., and Nagy, Andras

Subjects
Physiological aspects, Stem cell research, Somatic cells -- Physiological aspects
Abstract

Somatic cells that have lost their pluripotent properties through the acquisition of differentiation-associated epigenetic marks can be driven to acquire an induced pluripotent cell (iPSC) state by the forced expression [...], Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.

Published
2014
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19. Decellularization of porcine kidney with submicellar concentrations of SDS results in the retention of ECM proteins required for the adhesion and maintenance of human adult renal epithelial cells

Author

Bongolan, Tonya, primary, Whiteley, Jennifer, additional, Castillo-Prado, Jorge, additional, Fantin, Amanda, additional, Larsen, Brett, additional, Wong, Cassandra J., additional, Mazilescu, Laura, additional, Kawamura, Masataka, additional, Urbanellis, Peter, additional, Jonebring, Anna, additional, Salter, Eric, additional, Collingridge, Graham, additional, Gladdy, Rebecca, additional, Hicks, Ryan, additional, Gingras, Anne-Claude, additional, Selzner, Markus, additional, and Rogers, Ian M., additional

Published
2022
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22. Hydrogeology and Simulated Groundwater Availability in Reaches 3 and 4 of the Washita River Aquifer, Southern Oklahoma, 1980-2017.

Author

Rogers, Ian M. J., Smith, S. Jerrod, Gammill, Nicole C., Gillard, Natalie J., Lockmiller, Kayla A., Fetkovich, Evin J., Correll, Jessica S., and Hussey, Sean P.

Subjects
HYDROGEOLOGY, GROUNDWATER laws, AQUIFERS, DROUGHTS
Abstract

The 1973 Oklahoma Groundwater Law (Oklahoma Statutes §82-1020.5) requires that the Oklahoma Water Resources Board conduct hydrologic investigations of the State's aquifers to determine the maximum annual yield for each groundwater basin. Because more than 20 years have elapsed since the final order was issued, the U.S. Geological Survey, in cooperation with the Oklahoma Water Resources Board, conducted an updated hydrologic investigation and evaluated the effects of potential groundwater withdrawals on groundwater flow and availability in reaches 3 and 4 of the Washita River aquifer in southern Oklahoma for a study period spanning 1980-2017. A hydrogeologic framework and conceptual model were developed to guide the construction and calibration of a numerical model of the Washita River aquifer. The numerical model was calibrated to water-tablealtitude observations at selected wells, base-flow observations at selected U.S. Geological Survey streamgages, and the conceptual-model recharge. Three types of groundwater-availability scenarios were run using the calibrated numerical model. These scenarios were used to (1) estimate equal-proportionate-share pumping rates, (2) quantify the potential effects of projected well withdrawals on groundwater storage over a 50-year period, and (3) simulate the potential effects of a hypothetical 10-year drought. With Washita River main-stem inflows, the 20-, 40-, and 50-year equal-proportionate-share pumping rates under normal recharge conditions were about 3.08 acre-feet per acre per year for reach 3 and about 3.80 acre-feet per acre per year for reach 4. Projected 50-year pumping scenarios were used to simulate the effects of modified well withdrawal rates. Because well withdrawals were less than 1 percent of the calibrated numerical-model water budget, changes to the well pumping rates had little effect on Washita River base flows and groundwater storage in the Washita River aquifer. A hypothetical 10-year drought scenario was used to simulate the potential effects of a prolonged period of reduced recharge on groundwater storage. Groundwater storage at the end of the drought period was 4.6 percent less than the groundwater storage of the calibrated numerical model at the end of the drought period. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Correction: Won et al. Ex Vivo Perfusion Using a Mathematical Modeled, Controlled Gas Exchange Self-Contained Bioreactor Can Maintain a Mouse Kidney for Seven Days. Cells 2022, 11 , 1822.

Author

Won, Natalie, Castillo-Prado, Jorge, Tan, Xinzhu, Ford, John, Heath, David, Mazilescu, Laura Ioana, Selzner, Markus, and Rogers, Ian M.

Subjects
PERFUSION, MICE, GASES
Abstract

This document is a correction notice for an article titled "Ex Vivo Perfusion Using a Mathematical Modeled, Controlled Gas Exchange Self-Contained Bioreactor Can Maintain a Mouse Kidney for Seven Days." The correction addresses an error in the legend of Figure 2B, stating that the text in the manuscript's Results section is correct but the figure legend does not match. The correct legend is provided in the correction notice. The authors assure that this correction does not affect the scientific conclusions of the study. [Extracted from the article]

Published
2024
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29. Corrigendum: Genome-wide characterization of the routes to pluripotency

Author

Hussein, Samer M I, Puri, Mira C, Tonge, Peter D, Benevento, Marco, Corso, Andrew J, Clancy, Jennifer L, Mosbergen, Rowland, Li, Mira, Lee, Dong-Sung, Cloonan, Nicole, Wood, David L A, Munoz, Javier, Middleton, Robert, Korn, Othmar, Patel, Hardip R, White, Carl A, Shin, Jong-Yeon, Gauthier, Maely E, Cao, Kim-Anh Lê, Kim, Jong-Il, Mar, Jessica C, Shakiba, Nika, Ritchie, William, Rasko, John E J, Grimmond, Sean M, Zandstra, Peter W, Wells, Christine A, Preiss, Thomas, Seo, Jeong-Sun, Heck, Albert J R, Rogers, Ian M, Nagy, Andras, Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., and Sub Biomol.Mass Spect. and Proteomics

Published
2015

30. CD24 tracks divergent pluripotent states in mouse and human cells

Author

Shakiba, Nika, White, Carl A, Lipsitz, Yonatan Y, Yachie-Kinoshita, Ayako, Tonge, Peter D, Hussein, Samer M I, Puri, Mira C, Elbaz, Judith, Morrissey-Scoot, James, Li, Mira, Munoz Peralta, Javier, Benevento, Marco, Rogers, Ian M, Hanna, Jacob H, Heck, Albert J R, Wollscheid, Bernd, Nagy, Andras, Zandstra, Peter W, Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Ontario Government, Canadian Institutes of Health Research, and NSERC Vanier Canada Graduate Scholarship

Subjects
Cell biology, Human Embryonic Stem Cells, Induced Pluripotent Stem Cells, General Physics and Astronomy, Germ layer, Embryoid body, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Developmental biology, Animals, Humans, Induced pluripotent stem cell, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, Stem Cells, CD24 Antigen, Mouse Embryonic Stem Cells, General Chemistry, Cellular Reprogramming, Embryonic stem cell, Biological sciences, Epiblast, Stem cell, Reprogramming, 030217 neurology & neurosurgery, Germ Layers
Abstract

Reprogramming is a dynamic process that can result in multiple pluripotent cell types emerging from divergent paths. Cell surface protein expression is a particularly desirable tool to categorize reprogramming and pluripotency as it enables robust quantification and enrichment of live cells. Here we use cell surface proteomics to interrogate mouse cell reprogramming dynamics and discover CD24 as a marker that tracks the emergence of reprogramming-responsive cells, while enabling the analysis and enrichment of transgene-dependent (F-class) and -independent (traditional) induced pluripotent stem cells (iPSCs) at later stages. Furthermore, CD24 can be used to delineate epiblast stem cells (EpiSCs) from embryonic stem cells (ESCs) in mouse pluripotent culture. Importantly, regulated CD24 expression is conserved in human pluripotent stem cells (PSCs), tracking the conversion of human ESCs to more naive-like PSC states. Thus, CD24 is a conserved marker for tracking divergent states in both reprogramming and standard pluripotent culture., Nature Communications, 6, ISSN:2041-1723

Published
2015
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31. Small RNA changes en route to distinct cellular states of induced pluripotency

Author

Clancy, Jennifer L, Patel, Hardip R, Hussein, Samer M I, Tonge, Peter D, Cloonan, Nicole, Corso, Andrew J, Li, Mira, Lee, Dong-Sung, Shin, Jong-Yeon, Wong, Justin J L, Bailey, Charles G, Benevento, Marco, Munoz, Javier, Chuah, Aaron, Wood, David, Rasko, John E J, Heck, Albert J R, Grimmond, Sean M, Rogers, Ian M, Seo, Jeong-Sun, Wells, Christine A, Puri, Mira C, Nagy, Andras, Preiss, Thomas, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Molecular Pharmacy, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, and Molecular Pharmacy

Subjects
Gene isoform, Genetics, 0303 health sciences, Small RNA, Multidisciplinary, General Physics and Astronomy, General Chemistry, Biology, General Biochemistry, Genetics and Molecular Biology, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), 030220 oncology & carcinogenesis, Gene expression, DNA methylation, microRNA, Induced pluripotent stem cell, Reprogramming, 030304 developmental biology
Abstract

MicroRNAs (miRNAs) are critical to somatic cell reprogramming into induced pluripotent stem cells (iPSCs), however, exactly how miRNA expression changes support the transition to pluripotency requires further investigation. Here we use a murine secondary reprogramming system to sample cellular trajectories towards iPSCs or a novel pluripotent 'F-class' state and perform small RNA sequencing. We detect sweeping changes in an early and a late wave, revealing that distinct miRNA milieus characterize alternate states of pluripotency. miRNA isoform expression is common but surprisingly varies little between cell states. Referencing other omic data sets generated in parallel, we find that miRNA expression is changed through transcriptional and post-transcriptional mechanisms. miRNA transcription is commonly regulated by dynamic histone modification, while DNA methylation/demethylation consolidates these changes at multiple loci. Importantly, our results suggest that a novel subset of distinctly expressed miRNAs supports pluripotency in the F-class state, substituting for miRNAs that serve such roles in iPSCs.

Published
2014

33. Corrigendum: divergent reprogramming routes lead to alternative stem-cell states

Author

Tonge, Peter D., Corso, Andrew J., Monetti, Claudio, Hussein, Samer M.I., Puri, Mira C., Michael, Iacovos P., Li, Mira, Lee, Dong-Sung, Mar, Jessica C., Cloonan, Nicole, Wood, David L., Gauthier, Maely E., Korn, Othmar, Clancy, Jennifer L., Preiss, Thomas, Grimmond, Sean M., Shin, Jong-Yeon, Jeong-SunSeo, Wells, Christine A., Rogers, Ian M., and Nagy, Andras

Abstract

Nature 516, 192-197 (2014); doi:10.1038/nature14047 In this Article, the address listed as Nicole Cloonan's present address (QIMR Berghofer Medical Research Institute, Queensland 4006, Australia) should have been listed as her [...]

Published
2015
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34. Corrigendum: Genome-wide characterization of the routes to pluripotency

Author

Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Hussein, Samer M I, Puri, Mira C, Tonge, Peter D, Benevento, Marco, Corso, Andrew J, Clancy, Jennifer L, Mosbergen, Rowland, Li, Mira, Lee, Dong-Sung, Cloonan, Nicole, Wood, David L A, Munoz, Javier, Middleton, Robert, Korn, Othmar, Patel, Hardip R, White, Carl A, Shin, Jong-Yeon, Gauthier, Maely E, Cao, Kim-Anh Lê, Kim, Jong-Il, Mar, Jessica C, Shakiba, Nika, Ritchie, William, Rasko, John E J, Grimmond, Sean M, Zandstra, Peter W, Wells, Christine A, Preiss, Thomas, Seo, Jeong-Sun, Heck, Albert J R, Rogers, Ian M, Nagy, Andras, Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Hussein, Samer M I, Puri, Mira C, Tonge, Peter D, Benevento, Marco, Corso, Andrew J, Clancy, Jennifer L, Mosbergen, Rowland, Li, Mira, Lee, Dong-Sung, Cloonan, Nicole, Wood, David L A, Munoz, Javier, Middleton, Robert, Korn, Othmar, Patel, Hardip R, White, Carl A, Shin, Jong-Yeon, Gauthier, Maely E, Cao, Kim-Anh Lê, Kim, Jong-Il, Mar, Jessica C, Shakiba, Nika, Ritchie, William, Rasko, John E J, Grimmond, Sean M, Zandstra, Peter W, Wells, Christine A, Preiss, Thomas, Seo, Jeong-Sun, Heck, Albert J R, Rogers, Ian M, and Nagy, Andras

Published
2015

35. CD24 tracks divergent pluripotent states in mouse and human cells

Author

Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Shakiba, Nika, White, Carl A, Lipsitz, Yonatan Y, Yachie-Kinoshita, Ayako, Tonge, Peter D, Hussein, Samer M I, Puri, Mira C, Elbaz, Judith, Morrissey-Scoot, James, Li, Mira, Munoz Peralta, Javier, Benevento, Marco, Rogers, Ian M, Hanna, Jacob H, Heck, Albert J R, Wollscheid, Bernd, Nagy, Andras, Zandstra, Peter W, Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Shakiba, Nika, White, Carl A, Lipsitz, Yonatan Y, Yachie-Kinoshita, Ayako, Tonge, Peter D, Hussein, Samer M I, Puri, Mira C, Elbaz, Judith, Morrissey-Scoot, James, Li, Mira, Munoz Peralta, Javier, Benevento, Marco, Rogers, Ian M, Hanna, Jacob H, Heck, Albert J R, Wollscheid, Bernd, Nagy, Andras, and Zandstra, Peter W

Published
2015

37. Erratum: Corrigendum: Divergent reprogramming routes lead to alternative stem-cell states

Author

Tonge, Peter D., primary, Corso, Andrew J., additional, Monetti, Claudio, additional, Hussein, Samer M. I., additional, Puri, Mira C., additional, Michael, Iacovos P., additional, Li, Mira, additional, Lee, Dong-Sung, additional, Mar, Jessica C., additional, Cloonan, Nicole, additional, Wood, David L., additional, Gauthier, Maely E., additional, Korn, Othmar, additional, Clancy, Jennifer L., additional, Preiss, Thomas, additional, Grimmond, Sean M., additional, Shin, Jong-Yeon, additional, Seo, Jeong-Sun, additional, Wells, Christine A., additional, Rogers, Ian M., additional, and Nagy, Andras, additional

Published
2015
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38. Erratum: Corrigendum: Genome-wide characterization of the routes to pluripotency

Author

Hussein, Samer M. I., primary, Puri, Mira C., additional, Tonge, Peter D., additional, Benevento, Marco, additional, Corso, Andrew J., additional, Clancy, Jennifer L., additional, Mosbergen, Rowland, additional, Li, Mira, additional, Lee, Dong-Sung, additional, Cloonan, Nicole, additional, Wood, David L. A., additional, Munoz, Javier, additional, Middleton, Robert, additional, Korn, Othmar, additional, Patel, Hardip R., additional, White, Carl A., additional, Shin, Jong-Yeon, additional, Gauthier, Maely E., additional, Cao, Kim-Anh Lê, additional, Kim, Jong-Il, additional, Mar, Jessica C., additional, Shakiba, Nika, additional, Ritchie, William, additional, Rasko, John E. J., additional, Grimmond, Sean M., additional, Zandstra, Peter W., additional, Wells, Christine A., additional, Preiss, Thomas, additional, Seo, Jeong-Sun, additional, Heck, Albert J. R., additional, Rogers, Ian M., additional, and Nagy, Andras, additional

Published
2015
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39. Genome-wide characterization of the routes to pluripotency

Author

Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Molecular Pharmacy, Hussein, Samer M I, Puri, Mira C, Tonge, Peter D, Benevento, Marco, Corso, Andrew J, Clancy, Jennifer L, Mosbergen, Rowland, Li, Mira, Lee, Dong-Sung, Cloonan, Nicole, Wood, David L A, Munoz, Javier, Middleton, Robert, Korn, Othmar, Patel, Hardip R, White, Carl A, Shin, Jong-Yeon, Gauthier, Maely E, Lê Cao, Kim-Anh, Kim, Jong-Il, Mar, Jessica C, Shakiba, Nika, Ritchie, William, Rasko, John E J, Grimmond, Sean M, Zandstra, Peter W, Wells, Christine A, Preiss, Thomas, Seo, Jeong-Sun, Heck, Albert J R, Rogers, Ian M, Nagy, Andras, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Molecular Pharmacy, Hussein, Samer M I, Puri, Mira C, Tonge, Peter D, Benevento, Marco, Corso, Andrew J, Clancy, Jennifer L, Mosbergen, Rowland, Li, Mira, Lee, Dong-Sung, Cloonan, Nicole, Wood, David L A, Munoz, Javier, Middleton, Robert, Korn, Othmar, Patel, Hardip R, White, Carl A, Shin, Jong-Yeon, Gauthier, Maely E, Lê Cao, Kim-Anh, Kim, Jong-Il, Mar, Jessica C, Shakiba, Nika, Ritchie, William, Rasko, John E J, Grimmond, Sean M, Zandstra, Peter W, Wells, Christine A, Preiss, Thomas, Seo, Jeong-Sun, Heck, Albert J R, Rogers, Ian M, and Nagy, Andras

Published
2014

40. Small RNA changes en route to distinct cellular states of induced pluripotency

Author

Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Molecular Pharmacy, Clancy, Jennifer L, Patel, Hardip R, Hussein, Samer M I, Tonge, Peter D, Cloonan, Nicole, Corso, Andrew J, Li, Mira, Lee, Dong-Sung, Shin, Jong-Yeon, Wong, Justin J L, Bailey, Charles G, Benevento, Marco, Munoz, Javier, Chuah, Aaron, Wood, David, Rasko, John E J, Heck, Albert J R, Grimmond, Sean M, Rogers, Ian M, Seo, Jeong-Sun, Wells, Christine A, Puri, Mira C, Nagy, Andras, Preiss, Thomas, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Molecular Pharmacy, Clancy, Jennifer L, Patel, Hardip R, Hussein, Samer M I, Tonge, Peter D, Cloonan, Nicole, Corso, Andrew J, Li, Mira, Lee, Dong-Sung, Shin, Jong-Yeon, Wong, Justin J L, Bailey, Charles G, Benevento, Marco, Munoz, Javier, Chuah, Aaron, Wood, David, Rasko, John E J, Heck, Albert J R, Grimmond, Sean M, Rogers, Ian M, Seo, Jeong-Sun, Wells, Christine A, Puri, Mira C, Nagy, Andras, and Preiss, Thomas

Published
2014

41. Small RNA changes en route to distinct cellular states of induced pluripotency

Author

Clancy, Jennifer L., Patel, Hardip R., Hussein, Samer M. I., Tonge, Peter D., Cloonan, Nicole, Corso, Andrew J., Li, Mira, Lee, Dong-Sung, Shin, Jong-Yeon, Wong, Justin J. L., Bailey, Charles G., Benevento, Marco, Munoz, Javier, Chuah, Aaron, Wood, David, Rasko, John E. J., Heck, Albert J. R., Grimmond, Sean M., Rogers, Ian M., Seo, Jeong-Sun, Wells, Christine A., Puri, Mira C., Nagy, Andras, Preiss, Thomas, Clancy, Jennifer L., Patel, Hardip R., Hussein, Samer M. I., Tonge, Peter D., Cloonan, Nicole, Corso, Andrew J., Li, Mira, Lee, Dong-Sung, Shin, Jong-Yeon, Wong, Justin J. L., Bailey, Charles G., Benevento, Marco, Munoz, Javier, Chuah, Aaron, Wood, David, Rasko, John E. J., Heck, Albert J. R., Grimmond, Sean M., Rogers, Ian M., Seo, Jeong-Sun, Wells, Christine A., Puri, Mira C., Nagy, Andras, and Preiss, Thomas

Abstract

MicroRNAs (miRNAs) are critical to somatic cell reprogramming into induced pluripotent stem cells (iPSCs), however, exactly how miRNA expression changes support the transition to pluripotency requires further investigation. Here we use a murine secondary reprogramming system to sample cellular trajectories towards iPSCs or a novel pluripotent 'F-class' state and perform small RNA sequencing. We detect sweeping changes in an early and a late wave, revealing that distinct miRNA milieus characterize alternate states of pluripotency. miRNA isoform expression is common but surprisingly varies little between cell states. Referencing other omic data sets generated in parallel, we find that miRNA expression is changed through transcriptional and post-transcriptional mechanisms. miRNA transcription is commonly regulated by dynamic histone modification, while DNA methylation/demethylation consolidates these changes at multiple loci. Importantly, our results suggest that a novel subset of distinctly expressed miRNAs supports pluripotency in the F-class state, substituting for miRNAs that serve such roles in iPSCs.

Published
2014

42. Genome-wide characterization of the routes to pluripotency

Author

Hussein, Samer M. I., Puri, Mira C., Tonge, Peter D., Benevento, Marco, Corso, Andrew J., Clancy, Jennifer, Mosbergen, Rowland, Li, Mira, Lee, D. S., Cloonan, Nicole, Wood, David L. A., Munoz, Javier, Middleton, Robert, Korn, Othmar, Patel, Hardip, White, Carl A., Shin, Jong-Yeon, Gauthier, Maely E., Lê Cao, Kim-Anh, Kim, Jong-Il, Mar, J. C., Shakiba, Nika, Ritchie, William, Rasko, John E. J., Grimmond, Sean M., Zandstra, Peter W., Wells, Christine, Preiss, Thomas, Seo, Jeong-Sun, Heck, Albert J. R., Rogers, Ian M., Nagy, Andras, Hussein, Samer M. I., Puri, Mira C., Tonge, Peter D., Benevento, Marco, Corso, Andrew J., Clancy, Jennifer, Mosbergen, Rowland, Li, Mira, Lee, D. S., Cloonan, Nicole, Wood, David L. A., Munoz, Javier, Middleton, Robert, Korn, Othmar, Patel, Hardip, White, Carl A., Shin, Jong-Yeon, Gauthier, Maely E., Lê Cao, Kim-Anh, Kim, Jong-Il, Mar, J. C., Shakiba, Nika, Ritchie, William, Rasko, John E. J., Grimmond, Sean M., Zandstra, Peter W., Wells, Christine, Preiss, Thomas, Seo, Jeong-Sun, Heck, Albert J. R., Rogers, Ian M., and Nagy, Andras

Abstract

Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and-independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org.

Published
2014

43. An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator

Author

Lee, Dong-Sung, Shin, Jong-Yeon, Tonge, Peter D., Puri, Mira C., Lee, Seungbok, Park, Hansoo, Lee, Won-Chul, Hussein, Samer M. I., Bleazard, Thomas, Yun, Ji-Young, Kim, Jihye, Li, Mira, Cloonan, Nicole, Wood, David, Clancy, Jennifer L., Mosbergen, Rowland, Yi, Jae-Hyuk, Yang, Kap-Seok, Kim, Hyungtae, Rhee, Hwanseok, Wells, Christine A., Preiss, Thomas, Grimmond, Sean M., Rogers, Ian M., Nagy, Andras, Seo, Jeong-Sun, Lee, Dong-Sung, Shin, Jong-Yeon, Tonge, Peter D., Puri, Mira C., Lee, Seungbok, Park, Hansoo, Lee, Won-Chul, Hussein, Samer M. I., Bleazard, Thomas, Yun, Ji-Young, Kim, Jihye, Li, Mira, Cloonan, Nicole, Wood, David, Clancy, Jennifer L., Mosbergen, Rowland, Yi, Jae-Hyuk, Yang, Kap-Seok, Kim, Hyungtae, Rhee, Hwanseok, Wells, Christine A., Preiss, Thomas, Grimmond, Sean M., Rogers, Ian M., Nagy, Andras, and Seo, Jeong-Sun

Abstract

Reprogramming of somatic cells to induced pluripotent stem cells involves a dynamic rearrangement of the epigenetic landscape. To characterize this epigenomic roadmap, we have performed MethylC-seq, ChIP-seq (H3K4/K27/K36me3) and RNA-Seq on samples taken at several time points during murine secondary reprogramming as part of Project Grandiose. We find that DNA methylation gain during reprogramming occurs gradually, while loss is achieved only at the ESC-like state. Binding sites of activated factors exhibit focal demethylation during reprogramming, while ESC-like pluripotent cells are distinguished by extension of demethylation to the wider neighbourhood. We observed that genes with CpG-rich promoters demonstrate stable low methylation and strong engagement of histone marks, whereas genes with CpG-poor promoters are safeguarded by methylation. Such DNA methylation-driven control is the key to the regulation of ESC-pluripotency genes, including Dppa4, Dppa5a and Esrrb. These results reveal the crucial role that DNA methylation plays as an epigenetic switch driving somatic cells to pluripotency.

Published
2014

44. An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator

Author

Lee, Dong-Sung, primary, Shin, Jong-Yeon, additional, Tonge, Peter D., additional, Puri, Mira C., additional, Lee, Seungbok, additional, Park, Hansoo, additional, Lee, Won-Chul, additional, Hussein, Samer M. I., additional, Bleazard, Thomas, additional, Yun, Ji-Young, additional, Kim, Jihye, additional, Li, Mira, additional, Cloonan, Nicole, additional, Wood, David, additional, Clancy, Jennifer L., additional, Mosbergen, Rowland, additional, Yi, Jae-Hyuk, additional, Yang, Kap-Seok, additional, Kim, Hyungtae, additional, Rhee, Hwanseok, additional, Wells, Christine A., additional, Preiss, Thomas, additional, Grimmond, Sean M., additional, Rogers, Ian M., additional, Nagy, Andras, additional, and Seo, Jeong-Sun, additional

Published
2014
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48. AML Cells Have Altered Mitochondrial Biogenesis and Low Spare Reserve Capacity in Their Respiratory Chain That Renders Them Susceptible to Oxidative Metabolic Stress.

Author

Sriskanthadevan, Shrivani, primary, Chung, Timothy E, additional, Skrtic, Marko, additional, Jhas, Bozhena, additional, Hurren, Rose, additional, Gronda, Marcela, additional, Wang, Xiao Ming, additional, Jitkova, Yulia, additional, Sukhai, Mahadeo A., additional, Lin, Feng-Hsu, additional, Maclean, Neil, additional, Laister, Rob C., additional, Mullen, Peter, additional, Xie, Stephanie, additional, Penn, Linda, additional, Rogers, Ian M., additional, Dick, John E., additional, Minden, Mark D., additional, and Schimmer, Aaron D, additional

Published
2012
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50. Lysosomal Disruption Selectively Targets Leukemia Cells and Leukemia Stem Cells Through A Mechanism Related to Increased Reactive Oxygen Species Production

Author

Sukhai, Mahadeo A., primary, Hurren, Rose, additional, Rutledge, Angela, additional, Livak, Bozena, additional, Wang, Xiaoming, additional, Seneviratne, Ayesh, additional, Cusimano, Maria Christine, additional, Gebbia, Marinella, additional, Skrtic, Marko, additional, Sun, Hong, additional, Gronda, Marcela, additional, Spagnuolo, Paul A., additional, Urbanus, Malene, additional, Eppert, Kolja, additional, Dissanayake, Dilan, additional, Li, Xiaoming, additional, Sun, Thomas, additional, Vizeacoumar, Frederick, additional, Datti, Alessandro, additional, Ohashi, Pamela, additional, Wrana, Jeff L., additional, Rogers, Ian M., additional, Minden, Mark D., additional, Wang, Jean C.Y., additional, Dick, John E., additional, Corey, Seth J., additional, Nislow, Corey, additional, Giaever, Guri, additional, and Schimmer, Aaron D, additional

Published
2011
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