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Distinct Stem Cell Identities Converge into Shared Erythroid Stress in ERCC6L2 Disease and Shwachman-Diamond Syndrome

ERCC6L2 disease (ED) is a rare bone marrow failure syndrome caused by biallelic germline mutations in ERCC6L2. ED leads to accumulation of somatic TP53 mutations, myelodysplastic syndrome, and acute myeloid leukemia (AML) with erythroid predominance and poor prognosis. To delineate the transcriptomic events underlying delayed erythropoiesis and leukemic progression in ED, we leverage single-cell transcriptomics and single-cell TP53 genotyping of patient bone marrow across ED and Shwachman-Diamond syndrome. The dataset contains raw single-cell gene expression data (scRNA-seq), raw single-cell amplicon data (scAmp-seq), and curated metadata describing sample identity, cell populations, and disease classification. Related processed data will be available at ArrayExpress.

Type: RNASeq
Archive: Federated EGA Finland Federated EGA Node

2 Datasets 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000002724	This dataset contains .FASTQ files of targeted genotyping by single-cell amplicon sequencing (scAmp-seq) data of human bone marrow samples across ERCC6L2 disease (33 amplicon libraries from 15 samples from 9 patients) and Shwachman-Diamond syndrome (6 amplicon libraries from 4 samples from 3 patients). TP53 locus-specific scAmp-seq libraries were generated using a double-nested PCR approach resulting in four PCR rounds. Locus-specific reverse primers preserving the mutation site together with generic forward primers preserving the single-cell barcoding structure were designed. The resulting files were processed using CellRanger 6.0.2 pipelines with default parameters to generate FASTQ files.	Illumina NovaSeq 6000	19
EGAD50000002725	This dataset contains .FASTQ and .BAM files of scRNA-seq data of human bone marrow samples across ERCC6L2 disease (16 samples from 10 patients) and Shwachman-Diamond syndrome (6 samples from 5 patients). We applied single-cell RNA sequencing (scRNA-seq, 3’ 10X Genomics, Chromium Next GEM Single Cell 3' Gene Expression version 3.1 Dual Index chemistry) following manufacturer’s instructions. Libraries were sequenced on Illumina NovaSeq 6000 platform using read lengths: 28bp (Read 1), 10bp (i7 Index), 10bp (i5 Index) and 90bp (Read 2). The resulting files were processed using CellRanger 6.0.2 pipelines with default parameters to generate FASTQ files and count matrices, and the Illumina bcl2fastq v2.2.0 was used to run the mkfastq pipeline and alignment was done using GRCh38.	Illumina NovaSeq 6000	22

Publications	Citations
Distinct stem cell identities converge into shared erythroid stress in ERCC6L2 disease and Shwachman-Diamond syndrome. Langohr L, Kaaja I, Douglas SPM, Nebelung H, Koski J, Ikonen I, Katainen L, Maljanen K, Hakkarainen M, Räisänen T, Niinimäki R, Kakko S, Siitonen T, Adhikari S, Vähä-Koskela M, Heckman CA, Lahtela J, Wartiovaara-Kautto U, Pitkänen E, Kilpivaara O. Hemasphere 10: 2026 e70374	0