Smart-seq3 and Smart-seq3xpress single-cell RNA sequencing of bone marrow cells from MDS-RS patients
https://doi.org/10.48723/0f0c-p816
This dataset consists of Smart-seq3 single-cell RNA sequencing data of purified RS from the bone marrow and peripheral blood of 2 MDS-RS patients; and Smart-seq3xpress single-cell RNA sequencing data of FACS-sorted hematopoietic stem cells (HSC), multipotent progenitors (MPP), megakaryocyte-erythroid progenitors (MEP) and erythroblasts from 1 MDS-RS patient. 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: In brief, cells were sorted into 384-well plates containing 3uL Vapor-Lock (Qiagen) and 0.3uL lysis buffer consisting of 0.125 µM OligodT30VN (5'-Biotin-ACGAGCATCAGCAGCATACGAT30VN-3'; IDT) adjusted to reverse transcription (RT), 0.5mM dNTPs/each adjusted to RT volume, 0.1% Triton X-100, 5% PEG8000 adjusted to RT volume, 0.4u RNase Inhibitor (Takara Bio, 40 U/µL). After cell sorting plates were briefly centrifuged before storage at -80C. Before RT, plates were denatured at 72 degrees for 10 min followed by addition of 0.1 µL of RT mix; 25 mM Tris-HCL pH 8.4 (Fischer Scientific), 30mM NaCl (Ambion), 1 mM GTP (Thermo Fisher Scientific), 2.5 mM MgCl2 (Ambion), 8 mM DTT (Thermo Fisher Scientific), 0.25 U/µl RNase Inhibitor (Takara Bio), 0.75 µM Template Switching Oligo (TSO) (5′-Biotin-AGAGACAGATTGCGCAATGNNNNNNNNWWrGrGrG-3′; IDT) and 2 U/µl of Maxima H Minus reverse transcriptase (Thermo Fisher Scientific). Plates were quickly centrifuged after dispensing to ensure merge of lysis and RT volumes. RT was incubated at 42 °C for 90 minutes, followed by ten cycles of 50 °C for 2 minutes and 42 °C for 2 minutes. After RT, 0.6 µL PCR mix was dispensed to each well containing the following; 1× SeqAmp PCR buffer (Takara Bio), 0.025 U/µl of SeqAmp polymerase (Takara Bio) and 0.5 µM Smartseq3 forward and reverse primer. Plates were quickly spun down before being incubated as follows: 1 minute at 95 °C for initial denaturation, 14 cycles of 10 seconds at 98 °C, 30 seconds at 65 °C and 2–6 minutes at 68 °C. Final elongation was performed for 10 minutes at 72 °C.
The dataset consists of 2 folders:
- SS3_FACS_PB-BM_RS
- SS3xpress_FACS_HSC_MPP_MEP_EB
The folder SS3_FACS_PB-BM_RS contains 1 rds file, 3 txt files, and 1 compressed folder (tar.gz) with fastq files.
The folder SS3xpress_FACS_HSC_MPP_MEP_EB contains 1 rds file, 7 txt files, and 2 GNU zipped fastq files.
The documentation file File_list_SS3_SS3xpress.txt contains a full list of the files in the dataset.
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)
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]
Ethical Review
Ethical Review
Reviewer:
- Stockholm Ethical Review Board
Registration number:
2017/1090-31/4
Funding
Funding
Funding agency:
- Knut and Alice Wallenberg Foundation
Award number:
2017.0359
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.
Funding agency:
- Swedish Cancer Society
Award number:
19 0200
Funding agency:
- Swedish Cancer Society
Award number:
21 0340
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.
