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Your search keyword '"Hussein, Samer M. I."' showing total 23 results
Start Over Author "Hussein, Samer M. I." Publication Type Electronic Resources
23 results on '"Hussein, Samer M. I."'

1. 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, 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

2. 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, 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

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.

Published
2015

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks

Author

Benevento, Marco, Tonge, Peter D, Puri, Mira C, Hussein, Samer M I, Cloonan, Nicole, Wood, David L, Grimmond, Sean M, Nagy, Andras, Munoz, Javier, Heck, Albert J R, Benevento, Marco, Tonge, Peter D, Puri, Mira C, Hussein, Samer M I, Cloonan, Nicole, Wood, David L, Grimmond, Sean M, Nagy, Andras, Munoz, Javier, and Heck, Albert J R

Abstract

The ectopic expression of Oct4, Klf4, c-Myc and Sox2 (OKMS) transcription factors allows reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). The reprogramming process, which involves a complex network of molecular events, is not yet fully characterized. Here we perform a quantitative mass spectrometry-based analysis to probe in-depth dynamic proteome changes during somatic cell reprogramming. Our data reveal defined waves of proteome resetting, with the first wave occurring 48 h after the activation of the reprogramming transgenes and involving specific biological processes linked to the c-Myc transcriptional network. A second wave of proteome reorganization occurs in a later stage of reprogramming, where we characterize the proteome of two distinct pluripotent cellular populations. In addition, the overlay of our proteome resource with parallel generated -omics data is explored to identify post-transcriptionally regulated proteins involved in key steps during reprogramming.

Published
2014

11. Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks

Author

Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Molecular Pharmacy, Benevento, Marco, Tonge, Peter D, Puri, Mira C, Hussein, Samer M I, Cloonan, Nicole, Wood, David L, Grimmond, Sean M, Nagy, Andras, Munoz, Javier, Heck, Albert J R, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Molecular Pharmacy, Benevento, Marco, Tonge, Peter D, Puri, Mira C, Hussein, Samer M I, Cloonan, Nicole, Wood, David L, Grimmond, Sean M, Nagy, Andras, Munoz, Javier, and Heck, Albert J R

Published
2014

12. 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

13. 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

14. 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

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, 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

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

Author

Tonge, Peter D, Corso, Andrew J, Hussein, Samer M I, Monetti, Claudio, Puri, Mira C, Michael, Iacovos P, Li, Mira, Lee, DS, Clancy, Jennifer, Preiss, Thomas, Mar, JC, Cloonan, Nicole, Tonge, Peter D, Corso, Andrew J, Hussein, Samer M I, Monetti, Claudio, Puri, Mira C, Michael, Iacovos P, Li, Mira, Lee, DS, Clancy, Jennifer, Preiss, Thomas, Mar, JC, and Cloonan, Nicole

Abstract

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

17. 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

18. 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

19. 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

20. Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks

Author

Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Molecular Pharmacy, Benevento, Marco, Tonge, Peter D, Puri, Mira C, Hussein, Samer M I, Cloonan, Nicole, Wood, David L, Grimmond, Sean M, Nagy, Andras, Munoz, Javier, Heck, Albert J R, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Molecular Pharmacy, Benevento, Marco, Tonge, Peter D, Puri, Mira C, Hussein, Samer M I, Cloonan, Nicole, Wood, David L, Grimmond, Sean M, Nagy, Andras, Munoz, Javier, and Heck, Albert J R

Published
2014

21. Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks

Author

Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Molecular Pharmacy, Benevento, Marco, Tonge, Peter D, Puri, Mira C, Hussein, Samer M I, Cloonan, Nicole, Wood, David L, Grimmond, Sean M, Nagy, Andras, Munoz, Javier, Heck, Albert J R, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Molecular Pharmacy, Benevento, Marco, Tonge, Peter D, Puri, Mira C, Hussein, Samer M I, Cloonan, Nicole, Wood, David L, Grimmond, Sean M, Nagy, Andras, Munoz, Javier, and Heck, Albert J R

Published
2014

22. 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

23. 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

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