GEO series

Modelling Myeloma Dissemination in vitro with hMSC-Interacting Subpopulations of INA-6 Cells and their Aggregation/Detachment Dynamics

GSE261423 Homo sapiens (human) Single-cell RNA-seq 15 samples Submitted 2024/04/11 Platform GPL18573

At a glance

Single-cell RNA-seq · human · 15 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Homo sapiens (human)
Topic: Multiple myelomaThis series is part of our curated briefing on it.
Samples: 15 samples: 15 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Modeling Myeloma Dissemination In Vitro with hMSC-interacting Subpopulations of INA-6 Cells and Their Aggregation/Detachment DynamicsCancer research communications · 2024

Summary (written by the submitters)

Multiple myeloma involves early dissemination of malignant plasma cells across the bone marrow; however, the initial steps of dissemination remain unclear. Human bone marrow-derived mesenchymal stromal cells (hMSCs) stimulate myeloma cell expansion (e.g., IL-6) and simultaneously retain myeloma cells via chemokines (e.g., CXCL12) and adhesion factors.

Read the full summary ↓

Hence, we hypothesized that the imbalance between cell division and retention drives dissemination. We present an in vitro model using primary hMSCs co-cultured with INA-6 myeloma cells. Time-lapse microscopy revealed proliferation and attachment/detachment dynamics. Separation techniques (V-well adhesion assay and well plate sandwich centrifugation) were established to isolate MSC-interacting myeloma subpopulations that were characterized by RNAseq, cell viability and apoptosis. Results were correlated with gene expression data (n=837) and survival of myeloma patients (n=536). On dispersed hMSCs, INA-6 saturate hMSC-surface before proliferating into large homotypic aggregates, from which single cells detached completely. On confluent hMSCs, aggregates were replaced by strong heterotypic hMSC-INA-6 interactions, which modulated apoptosis time-dependently. Only INA-6 daughter cells (nMA-INA6) detached from hMSCs by cell division but sustained adherence to hMSC-adhering mother cells (MA-INA6). Isolated nMA-INA6 indicated hMSC-autonomy through superior viability after IL6 withdrawal and upregulation of proliferation-related genes. MA-INA6 upregulated adhesion and retention factors (CXCL12), that, intriguingly, were highly expressed in myeloma samples from patients with longer overall and progression-free survival, but their expression decreased in relapsed myeloma samples. Altogether, in vitro dissemination of INA-6 is driven by detaching daughter cells after a cycle of hMSC-(re)attachment and proliferation, involving adhesion factors that represent a bone marrow-retentive phenotype with potential clinical relevance.

Published in

Modeling Myeloma Dissemination In Vitro with hMSC-interacting Subpopulations of INA-6 Cells and Their Aggregation/Detachment Dynamics

Kuric M, Beck S, Schneider D et al. · Cancer research communications 2024 · PMID 38598843 · doi:10.1158/2767-9764.CRC-23-0411

This dataset

Open GSE261423 in finder → Find more human RNA-seq datasets → Multiple myeloma landscape →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE261423_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1086919 and SRA study SRP494780. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38598843) ↗

Study design

15 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 15 sample titles: 15 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8143797 CM-INA6 / F1, hMSC-conditioned Medium F1 (WPSC Control) (biol rep 1)
GSM8143798 nMA-INA6 / F2, Removed by Centrifugation F2 (WPSC) (biol rep 1)
GSM8143799 MA-INA6 / F3, Remaining after Centrifugation F3 (WPSC) (biol rep 1)
GSM8143800 CM-INA6 / F1, hMSC-conditioned Medium F1 (WPSC Control) (biol rep 2)
GSM8143801 nMA-INA6 / F2, Removed by Centrifugation F2 (WPSC) (biol rep 2)
GSM8143802 MA-INA6 / F3, Remaining after Centrifugation F3 (WPSC) (biol rep 2)
GSM8143803 CM-INA6 / F1, hMSC-conditioned Medium F1 (WPSC Control) (biol rep 3)
GSM8143804 nMA-INA6 / F2, Removed by Centrifugation F2 (WPSC) (biol rep 3)
GSM8143805 MA-INA6 / F3, Remaining after Centrifugation F3 (WPSC) (biol rep 3)
GSM8143806 CM-INA6 / F1, hMSC-conditioned Medium F1 (WPSC Control) (biol rep 4)
GSM8143807 nMA-INA6 / F2, Removed by Centrifugation F2 (WPSC) (biol rep 4)
GSM8143808 MA-INA6 / F3, Remaining after Centrifugation F3 (WPSC) (biol rep 4)
GSM8143809 CM-INA6 / F1, hMSC-conditioned Medium F1 (WPSC Control) (biol rep 5)
GSM8143810 nMA-INA6 / F2, Removed by Centrifugation F2 (WPSC) (biol rep 5)
GSM8143811 MA-INA6 / F3, Remaining after Centrifugation F3 (WPSC) (biol rep 5)

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