Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging

In this study we characterised the consequences of DNMT3A- and TET2-mutations in human clonal haematopoiesis. We screened 195 bone marrow samples for mutations by targeted DNA sequencing, and sequenced 99 paired peripheral blood samples to compare mutation detection between bone marrow and blood. We performed single-cell analysis with TARGET-seq+ on 13 samples (4 controls and 9 clonal haematopoiesis samples), which combines single-cell genotyping for targeted mutations with whole transcriptome sequencing on FACS sorted cells. Single-cell genotyping and transcriptomes were sequenced separately and linked by common single-cell identifiers.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

3 Datasets 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001011083	Targeted DNA sequencing was performed on 195 bone marrow samples to identify cases of clonal haematopoiesis, and on 99 paired peripheral blood samples. The SeqCap EZ HyperCap protocol was followed, and targeted capture performed against a panel of 97 genes recurrently mutated in myeloid malignancies and clonal hematopoiesis. One BAM file (mapped to the hg38 reference genome) is provided per sample.	NextSeq 500	294
EGAD00001011150	Single-cell genotyping data for bone marrow samples from 9 cases with clonal hematopoiesis and 1 control sample. The TARGET-seq+ protocol was used to generate plate-based 3' transcriptome data. For details on cell sorting and the TARGET-seq+ protocol see the methods section of the manuscript. One FASTQ file is provided per cell. Cells are named with their plate and well IDs and the subject ID. Empty wells (no-cell controls) are named "blank". Corresponding transcriptome files use the same naming with the "_transcriptome" suffix.	NextSeq 500	11712
EGAD00001011175	Single-cell whole transcriptome sequencing data for bone marrow samples from 9 cases with clonal hematopoiesis and 4 control samples. The TARGET-seq+ protocol was used to generate plate-based 3' transcriptome data. For details on cell sorting and the TARGET-seq+ protocol see the methods section of the manuscript. One FASTQ file is provided per cell. Cells are named with their plate and well IDs and the subject ID. Empty wells (no-cell controls) are named "blank". Corresponding genotyping files use the same naming without the "_transcriptome" suffix.	Illumina NovaSeq 6000	14073

Publications	Citations
Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging. Jakobsen NA, Turkalj S, Zeng AGX, Stoilova B, Metzner M, Rahmig S, Nagree MS, Shah S, Moore R, Usukhbayar B, Angulo Salazar M, Gafencu GA, Kennedy A, Newman S, Kendrick BJL, Taylor AH, Afinowi-Luitz R, Gundle R, Watkins B, Wheway K, Beazley D, Murison A, Aguilar-Navarro AG, Flores-Figueroa E, Dakin SG, Carr AJ, Nerlov C, Dick JE, Xie SZ, Vyas P. Cell Stem Cell 31: 2024 1127-1144.e17	4

Publications

Citations

Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging.
Jakobsen NA, Turkalj S, Zeng AGX, Stoilova B, Metzner M, Rahmig S, Nagree MS, Shah S, Moore R, Usukhbayar B, Angulo Salazar M, Gafencu GA, Kennedy A, Newman S, Kendrick BJL, Taylor AH, Afinowi-Luitz R, Gundle R, Watkins B, Wheway K, Beazley D, Murison A, Aguilar-Navarro AG, Flores-Figueroa E, Dakin SG, Carr AJ, Nerlov C, Dick JE, Xie SZ, Vyas P. Cell Stem Cell 31: 2024 1127-1144.e17