Bulk RNA sequencing of bone marrow cells from MDS-RS patients and healthy donors
https://doi.org/10.48723/41wa-yv42
This dataset consists of bulk RNA sequencing data of MACS-separated bone marrow cells (CD34+ stem cells, GPA+ erythroblasts, CD71+ reticulocytes, ring sideroblasts and siderocytes) obtained from multiple healthy bone marrow donors and MDS-RS patients. A second minibulk dataset is included, where CD34+ and GPA+ cells were treated with cycloheximide or left untreated. The objective of this data collection was to assess several parameters on how the bone marrow of MDS-RS patients differs from that of healthy donors.
This dataset includes raw sequencing data in .fastq format, processed count matrices and associated pseudonymized metadata.
Processing:
Bulk:
CD34+ HSPC samples, mixed GPA+ erythroblast samples and CD71+ PB reticulocyte samples (RetPB) were isolated through MACS. RS and siderocytes were obtained through MACS+FACS. Cells were lysed in RLT (Qiagen) + 40 mM dithiothreitol (Sigma-Aldrich) and RNA extraction was performed with RNeasy Micro Kit (Qiagen) with RNase-free DNase treatment according to the manufacturer’s protocol. RNA integrity numbers (RIN) were estimated using Agilent RNA 6000 Pico Kits (Agilent Technologies, CA, USA). A minimum RIN value of 6.5 was considered adequate.
Minibulk:
Minibulk RNAseq was performed for assessment of cycloheximide treatment effects in CD34+ and GPA+ cell populations. The library preparation procedure was performed using the Xpress Genomics bulk RNA-seq kit v1, automated on a SP960 liquid handler (MGI Tech). In short, the library preparation procedure denatures RNA samples in presence of oligo-dT primer, which is followed by reverse transcription of RNA with a template-switching procedure and pre-amplification of full-length cDNA for 10 PCR cycles. cDNA was subsequently tagmented using Tn5 (TDE1 Tagment DNA Enzyme; Illumina) and reactions quenched after 10 min at 55 °C by addition of 0.2 % SDS (Sigma-Aldrich). Tagmented DNA was indexed using custom dual-unique Nextera index primers in a 12 cycle PCR reaction. Indexed libraries were cleaned up using SPRI beads in 22% PEG8000 buffer and eluted in 12 µL H2O.
The dataset consists of 2 folders:
- Bulk_Main
- Minibulk_Cycloheximide
The folder Bulk_Main contains 67 GNU zipped fastq files, 1 tsv file, and 1 txt file.
The folder Minibulk_Cycloheximide contains 2 GNU zipped fastq files, and 4 txt files.
The documentation file File_list_BulkMinibulk.txt contains a full list of the files in the dataset.
The total size of the dataset is approximately 360 GB.
Documentation files
Documentation files
Citation and access
Citation and access
Data access level:
Creator/Principal investigator(s):
Research principal:
Data contains personal data:
Yes
Type of personal data:
Genetic and biological data of patients
Code key exists:
Yes
Sensitive personal data:
Yes
Citation:
License:
Language:
Method and outcome
Method and outcome
Unit of analysis:
Population:
Patients with Myelodysplastic neoplasms with ring sideroblasts (MDS-RS) and healthy donors
Study design:
- Preclinical study
Sampling procedure:
Description of sampling:
Bone marrow (BM) and/or peripheral blood (PB) samples were collected from 36 MDS-RS and 3 MDS non-RS patients evaluated at Karolinska University Hospital, Huddinge, Sweden. Diagnostic procedures were performed according to the European LeukemiaNet recommendation and WHO classification for myeloid neoplasms. As the specific purpose was to dissect the pathobiology of SF3B1-mutant MDS-RS, all MDS-RS patients belonged to the SF3B1α category in the IPSS-M risk classification. RS presence was quantified according to standard clinical practice. Additional samples were collected from a total of 40 healthy normal bone marrow (NBM) donors for control purposes. Please note that a deidentified donor and experiment index is provided in the companion publication for this dataset, including clinical and mutational status. All source material was provided with written informed consent for research use, given in accordance with the Declaration of Helsinki.
Samples/material - Existing from scientific collection/biobank
Samples/material - Existing from scientific collection/biobank
Name:
Karolinska Institutet MDS biobank
Type(s) of sample:
Bone marrow cells
Administrative information
Administrative information
Responsible department/unit:
Department of Medicine, Huddinge [H7]
Contributor(s):
- Gabriele Todisco – Karolinska Institutet - Department of Medicine, Huddinge / Center for Hematology and Regenerative Medicine (HERM)
Ethical Review
Ethical Review
Reviewer:
- Stockholm Ethical Review Board
Registration number:
2017/1090-31/4
Funding
Funding
Funding agency:
- Swedish Cancer Society
Award number:
21 0340
Funding agency:
- Knut and Alice Wallenberg Foundation
Award number:
2017.0359
Funding agency:
- Swedish Cancer Society
Award number:
19 0200
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2021-01404_VR
Award title:
Disease mechanisms and targeted treatment in myelodysplastic syndromes
Funding information:
This translational research program aims at improving outcome for patients with myelodysplastic syndromes (MDS) by unravelling cellular and molecular mechanisms underlying disease features and response to treatment. Using a world-unique database of clinically annotated MDS patients who have undergone targeted DNA sequencing and RNA sequencing of CD34+ BM cells and has been complemented with comprehensive information regarding transfusion patterns and response to treatment we aim to develop novel predictive models for estimation of age-related survival loss, risk for progression, and optimal management and treatment. By using advanced culture models for human hemopoietic stem cell (HSC) biology and erythroid maturation in combination with single cell sequencing we will explore SF3B1 mutated MDS with ring sideroblasts with the aim to understand the clonal advantage of mutated over normal HSC and explore new molecular routes to prevent ineffective erythropoiesis and chronic transfusion dependency. Finally, we aim to implement and further improve recently developed methods for personalized minimal residual disease monitoring in a prospective clinical trial and thereby improve the cure rate after allogeneic stem cell transplantation in high-risk MDS. The long-term goal is to implement precision medicine in MDS in order to be able to predict and implement optimal management for each patient.
Topic and keywords
Topic and keywords
Swedish Standard Classification of Research Subjects 2025:
Publications
Publications
Citation:
Moura PL, Mortera Blanco T, Hofman IJ, Todisco G, Kretzschmar WW, Björklund AC, Creignou M, Hagemann-Jensen M, Ziegenhain C, Cabrerizo Granados D, Barbosa I, Walldin G, Jansson M, Ashley N, Mead AJ, Lundin V, Dimitriou M, Yoshizato T, Woll PS, Ogawa S, Sandberg R, Jacobsen SW, Hellström-Lindberg E. Erythroid differentiation enhances RNA mis-splicing in SF3B1-mutant myelodysplastic syndromes with ring sideroblasts. Cancer Res. 2023 Nov 3. doi: 10.1158/0008-5472.CAN-23-3038.
