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Series GSE247968 Query DataSets for GSE247968
Status Public on Mar 14, 2024
Title Cell of origin epigenetic priming determines susceptibility to Tet2 oncogenic mutation [scRNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Hematopoietic stem cell mutations can result in clonal hematopoiesis (CHIP) but the clinical outcomes are heterogeneous. The nature of the founder mutation and secondary mutations likely drive emergent neoplastic disease. We investigated how the cell state where the TET2 mutation occurs affects susceptibility to that commonly occurring CH mutation. Here, we provide evidence that risk is written in the epigenome of the cell of origin. By characterizing cell states that underlie myeloid differentiation and linking this information to an inducible system to assess myeloid progenitor clones, we provide evidence that epigenetic markers of the cell where Tet2 mutation occurs stratifies clonal behaviors. Specifically, Sox4 fosters a global cell state of high sensitization towards Tet2 KO. Using GMP and primary HSC models, we show that Sox4 promotes cell dedifferentiation, alters cell metabolism and increases the in vivo clonal output of mutant cells. Our results validate the hypothesis that epigenetic features can predispose specific clones for dominance and explain why an identical mutation can result in different outcomes.
Overall design Bone marrow hematopoietic progenitor cells from inducible Tet2 mutant mice or matched controls were profiled using the Chromium Single Cell Reagent Kit v3.1. Our dataset included populations spanning from HSC to mature myeloid effector cells (Lin- progenitors, CD11b+ cells), and sorted GMPs (Lin- cKit+ Sca1- CD34+ CD16/32+).
Contributor(s) Duarte F, Schiroli G, Kartha V
Citation(s) 38773071
Submission date Nov 16, 2023
Last update date Jun 06, 2024
Contact name Fabiana Duarte
Organization name Harvard University
Department HSCRB
Lab Buenrostro lab
Street address 7 Divinity Avenue
City Cambridge
State/province Massachusetts
ZIP/Postal code 02138
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM7903906 GMP_Control_Rep2
GSM7903907 GMP_Tet2_Rep2
GSM7903908 Lin_neg_CD11b_Control_Rep2
This SubSeries is part of SuperSeries:
GSE247970 Cell of origin epigenetic priming determines susceptibility to Tet2 oncogenic mutation
BioProject PRJNA1041323

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Supplementary file Size Download File type/resource
GSE247968_GMP_scRNAseq.barcodes.txt.gz 41.1 Kb (ftp)(http) TXT
GSE247968_GMP_scRNAseq.genes.txt.gz 67.8 Kb (ftp)(http) TXT
GSE247968_GMP_scRNAseq_cellMeta.txt.gz 106.0 Kb (ftp)(http) TXT
GSE247968_GMP_scRNAseq_raw_counts.mtx.gz 73.0 Mb (ftp)(http) MTX
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