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Series GSE146755 Query DataSets for GSE146755
Status Public on Oct 13, 2020
Title Smc3 regulates B-cell transit through germinal centers and restricts their malignant transformation (single-cell RNA-seq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary During the germinal center (GC) reaction, B-cells undergo extensive redistribution of cohesin complex and 3D re-organization of their genomes. Yet, the significance of cohesin and architectural programming in the humoral immune response is unknown. Herein we report that conditional homozygous deletion of cohesin subunit Smc3 abrogated GC formation, yet in marked contrast, Smc3 haploinsufficiency induced GC hyperplasia, skewing of GC polarity and impaired plasma cell differentiation. Transcriptional and architectural profiling revealed defects in GC terminal differentiation programs controlled by lymphoma epigenetic tumor suppressors Tet2 and Kmt2d, and failure of Smc3+/- GC B-cells to switch from B-cell to plasma cell lineage factors. There was also impaired connectivity of gene regulatory elements controlling tumor suppressor genes, and accordingly Smc3 haploinsufficiency accelerated lymphomagenesis in mice with constitutive Bcl6 expression. Collectively, our data indicate a dose dependent function for cohesin in humoral immunity to facilitate the B-cell to plasma cell lineage switch, while restricting their malignant transformation.
Overall design Six samples total: germinal center and post-germinal center B-cells R26-LSL-YFPwt/fl;Smc3wt/fl;Cγ1-cre (WT, three biological replicates); germinal center and post-germinal center B-cells R26-LSL-YFPwt/fl;Cγ1-cre (SMC3, three biological replicates) of 10 weeks-old female mice immunized with SRBC and euthanized 8 days post-immunization. Samples were multiplexed.
Contributor(s) Rivas MA, Meydan C, Chin CR, Challman MF, Kim D, Binder B, Kloetgen A, Viny A, Teater M, McNally D, Doane AS, Béguelin W, Calvo Fernández MT, Shen H, Levine RL, Chen Z, Tsirigos A, Elemento O, Mason CE, Melnick AM
Citation(s) 33432228
Submission date Mar 10, 2020
Last update date Jan 19, 2021
Contact name Cem Meydan
Organization name Weill Cornell Medical College
Department Physiology & Biophysics
Lab Melnick Lab & Mason Lab
Street address 1305 York
City New York
State/province New York
ZIP/Postal code 10065
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (1)
GSM4405431 WT and SMC single cells
This SubSeries is part of SuperSeries:
GSE143852 Smc3 regulates B-cell transit through germinal centers and restricts their malignant transformation
BioProject PRJNA611811
SRA SRP252260

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE146755_RAW.tar 1.3 Mb (http)(custom) TAR (of CSV)
GSE146755_barcode2Index.csv.gz 86.6 Kb (ftp)(http) CSV
GSE146755_barcode_location.txt.gz 516 b (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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