Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]

Publication Date:
2018-02-16
Publisher:
Cold Spring Harbor Laboratory Press
Print ISSN:
0890-9369
Topics:
Biology
Published by:
http://www.cshlpress.com/
_version_ 1836398798080835584
autor Miyai, T., Takano, J., Endo, T. A., Kawakami, E., Agata, Y., Motomura, Y., Kubo, M., Kashima, Y., Suzuki, Y., Kawamoto, H., Ikawa, T.
beschreibung Stem cell fate is orchestrated by core transcription factors (TFs) and epigenetic modifications. Although regulatory genes that control cell type specification are identified, the transcriptional circuit and the cross-talk among regulatory factors during cell fate decisions remain poorly understood. To identify the "time-lapse" TF networks during B-lineage commitment, we used multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system in which virtually all cells became B cells within 6 d by simply withdrawing 4-hydroxytamoxifen (4-OHT). Transcriptome and epigenome analysis at multiple time points revealed that ~10%–30% of differentially expressed genes were virtually controlled by the core TFs, including E2A, EBF1, and PAX5. Strikingly, we found unexpected transcriptional priming before the onset of the key TF program. Inhibition of the immediate early genes such as Nr4a2 , Klf4 , and Egr1 severely impaired the generation of B cells. Integration of multiple data sets, including transcriptome, protein interactome, and epigenome profiles, identified three representative transcriptional circuits. Single-cell RNA sequencing (RNA-seq) analysis of lymphoid progenitors in bone marrow strongly supported the three-step TF network model during specification of multipotent progenitors toward B-cell lineage in vivo. Thus, our findings will provide a blueprint for studying the normal and neoplastic development of B lymphocytes.
citation_standardnr 6166226
datenlieferant ipn_articles
feed_id 1644
feed_publisher Cold Spring Harbor Laboratory Press
feed_publisher_url http://www.cshlpress.com/
insertion_date 2018-02-16
journalissn 0890-9369
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher Cold Spring Harbor Laboratory Press
quelle Genes & Development
relation http://genesdev.cshlp.org/cgi/content/short/32/2/112?rss=1
search_space articles
shingle_author_1 Miyai, T., Takano, J., Endo, T. A., Kawakami, E., Agata, Y., Motomura, Y., Kubo, M., Kashima, Y., Suzuki, Y., Kawamoto, H., Ikawa, T.
shingle_author_2 Miyai, T., Takano, J., Endo, T. A., Kawakami, E., Agata, Y., Motomura, Y., Kubo, M., Kashima, Y., Suzuki, Y., Kawamoto, H., Ikawa, T.
shingle_author_3 Miyai, T., Takano, J., Endo, T. A., Kawakami, E., Agata, Y., Motomura, Y., Kubo, M., Kashima, Y., Suzuki, Y., Kawamoto, H., Ikawa, T.
shingle_author_4 Miyai, T., Takano, J., Endo, T. A., Kawakami, E., Agata, Y., Motomura, Y., Kubo, M., Kashima, Y., Suzuki, Y., Kawamoto, H., Ikawa, T.
shingle_catch_all_1 Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
Stem cell fate is orchestrated by core transcription factors (TFs) and epigenetic modifications. Although regulatory genes that control cell type specification are identified, the transcriptional circuit and the cross-talk among regulatory factors during cell fate decisions remain poorly understood. To identify the "time-lapse" TF networks during B-lineage commitment, we used multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system in which virtually all cells became B cells within 6 d by simply withdrawing 4-hydroxytamoxifen (4-OHT). Transcriptome and epigenome analysis at multiple time points revealed that ~10%–30% of differentially expressed genes were virtually controlled by the core TFs, including E2A, EBF1, and PAX5. Strikingly, we found unexpected transcriptional priming before the onset of the key TF program. Inhibition of the immediate early genes such as Nr4a2 , Klf4 , and Egr1 severely impaired the generation of B cells. Integration of multiple data sets, including transcriptome, protein interactome, and epigenome profiles, identified three representative transcriptional circuits. Single-cell RNA sequencing (RNA-seq) analysis of lymphoid progenitors in bone marrow strongly supported the three-step TF network model during specification of multipotent progenitors toward B-cell lineage in vivo. Thus, our findings will provide a blueprint for studying the normal and neoplastic development of B lymphocytes.
Miyai, T., Takano, J., Endo, T. A., Kawakami, E., Agata, Y., Motomura, Y., Kubo, M., Kashima, Y., Suzuki, Y., Kawamoto, H., Ikawa, T.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_catch_all_2 Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
Stem cell fate is orchestrated by core transcription factors (TFs) and epigenetic modifications. Although regulatory genes that control cell type specification are identified, the transcriptional circuit and the cross-talk among regulatory factors during cell fate decisions remain poorly understood. To identify the "time-lapse" TF networks during B-lineage commitment, we used multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system in which virtually all cells became B cells within 6 d by simply withdrawing 4-hydroxytamoxifen (4-OHT). Transcriptome and epigenome analysis at multiple time points revealed that ~10%–30% of differentially expressed genes were virtually controlled by the core TFs, including E2A, EBF1, and PAX5. Strikingly, we found unexpected transcriptional priming before the onset of the key TF program. Inhibition of the immediate early genes such as Nr4a2 , Klf4 , and Egr1 severely impaired the generation of B cells. Integration of multiple data sets, including transcriptome, protein interactome, and epigenome profiles, identified three representative transcriptional circuits. Single-cell RNA sequencing (RNA-seq) analysis of lymphoid progenitors in bone marrow strongly supported the three-step TF network model during specification of multipotent progenitors toward B-cell lineage in vivo. Thus, our findings will provide a blueprint for studying the normal and neoplastic development of B lymphocytes.
Miyai, T., Takano, J., Endo, T. A., Kawakami, E., Agata, Y., Motomura, Y., Kubo, M., Kashima, Y., Suzuki, Y., Kawamoto, H., Ikawa, T.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_catch_all_3 Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
Stem cell fate is orchestrated by core transcription factors (TFs) and epigenetic modifications. Although regulatory genes that control cell type specification are identified, the transcriptional circuit and the cross-talk among regulatory factors during cell fate decisions remain poorly understood. To identify the "time-lapse" TF networks during B-lineage commitment, we used multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system in which virtually all cells became B cells within 6 d by simply withdrawing 4-hydroxytamoxifen (4-OHT). Transcriptome and epigenome analysis at multiple time points revealed that ~10%–30% of differentially expressed genes were virtually controlled by the core TFs, including E2A, EBF1, and PAX5. Strikingly, we found unexpected transcriptional priming before the onset of the key TF program. Inhibition of the immediate early genes such as Nr4a2 , Klf4 , and Egr1 severely impaired the generation of B cells. Integration of multiple data sets, including transcriptome, protein interactome, and epigenome profiles, identified three representative transcriptional circuits. Single-cell RNA sequencing (RNA-seq) analysis of lymphoid progenitors in bone marrow strongly supported the three-step TF network model during specification of multipotent progenitors toward B-cell lineage in vivo. Thus, our findings will provide a blueprint for studying the normal and neoplastic development of B lymphocytes.
Miyai, T., Takano, J., Endo, T. A., Kawakami, E., Agata, Y., Motomura, Y., Kubo, M., Kashima, Y., Suzuki, Y., Kawamoto, H., Ikawa, T.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_catch_all_4 Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
Stem cell fate is orchestrated by core transcription factors (TFs) and epigenetic modifications. Although regulatory genes that control cell type specification are identified, the transcriptional circuit and the cross-talk among regulatory factors during cell fate decisions remain poorly understood. To identify the "time-lapse" TF networks during B-lineage commitment, we used multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system in which virtually all cells became B cells within 6 d by simply withdrawing 4-hydroxytamoxifen (4-OHT). Transcriptome and epigenome analysis at multiple time points revealed that ~10%–30% of differentially expressed genes were virtually controlled by the core TFs, including E2A, EBF1, and PAX5. Strikingly, we found unexpected transcriptional priming before the onset of the key TF program. Inhibition of the immediate early genes such as Nr4a2 , Klf4 , and Egr1 severely impaired the generation of B cells. Integration of multiple data sets, including transcriptome, protein interactome, and epigenome profiles, identified three representative transcriptional circuits. Single-cell RNA sequencing (RNA-seq) analysis of lymphoid progenitors in bone marrow strongly supported the three-step TF network model during specification of multipotent progenitors toward B-cell lineage in vivo. Thus, our findings will provide a blueprint for studying the normal and neoplastic development of B lymphocytes.
Miyai, T., Takano, J., Endo, T. A., Kawakami, E., Agata, Y., Motomura, Y., Kubo, M., Kashima, Y., Suzuki, Y., Kawamoto, H., Ikawa, T.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_title_1 Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
shingle_title_2 Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
shingle_title_3 Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
shingle_title_4 Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
timestamp 2025-06-30T23:32:47.120Z
titel Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
titel_suche Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells [Research Papers]
topic W
uid ipn_articles_6166226