Single-cell transcriptomics and epigenomics unravel the role of monocytes in neuroblastoma bone marrow metastasis
© 2023. The Author(s)..
Metastasis is the major cause of cancer-related deaths. Neuroblastoma (NB), a childhood tumor has been molecularly defined at the primary cancer site, however, the bone marrow (BM) as the metastatic niche of NB is poorly characterized. Here we perform single-cell transcriptomic and epigenomic profiling of BM aspirates from 11 subjects spanning three major NB subtypes and compare these to five age-matched and metastasis-free BM, followed by in-depth single cell analyses of tissue diversity and cell-cell interactions, as well as functional validation. We show that cellular plasticity of NB tumor cells is conserved upon metastasis and tumor cell type composition is NB subtype-dependent. NB cells signal to the BM microenvironment, rewiring via macrophage mgration inhibitory factor and midkine signaling specifically monocytes, which exhibit M1 and M2 features, are marked by activation of pro- and anti-inflammatory programs, and express tumor-promoting factors, reminiscent of tumor-associated macrophages. The interactions and pathways characterized in our study provide the basis for therapeutic approaches that target tumor-to-microenvironment interactions.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
---|---|
Enthalten in: |
Nature communications - 14(2023), 1 vom: 26. Juni, Seite 3620 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Fetahu, Irfete S [VerfasserIn] |
---|
Links: |
---|
Themen: |
---|
Anmerkungen: |
Date Completed 28.06.2023 Date Revised 01.07.2023 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.1038/s41467-023-39210-0 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM358665337 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM358665337 | ||
003 | DE-627 | ||
005 | 20231226075229.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1038/s41467-023-39210-0 |2 doi | |
028 | 5 | 2 | |a pubmed24n1195.xml |
035 | |a (DE-627)NLM358665337 | ||
035 | |a (NLM)37365178 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Fetahu, Irfete S |e verfasserin |4 aut | |
245 | 1 | 0 | |a Single-cell transcriptomics and epigenomics unravel the role of monocytes in neuroblastoma bone marrow metastasis |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 28.06.2023 | ||
500 | |a Date Revised 01.07.2023 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2023. The Author(s). | ||
520 | |a Metastasis is the major cause of cancer-related deaths. Neuroblastoma (NB), a childhood tumor has been molecularly defined at the primary cancer site, however, the bone marrow (BM) as the metastatic niche of NB is poorly characterized. Here we perform single-cell transcriptomic and epigenomic profiling of BM aspirates from 11 subjects spanning three major NB subtypes and compare these to five age-matched and metastasis-free BM, followed by in-depth single cell analyses of tissue diversity and cell-cell interactions, as well as functional validation. We show that cellular plasticity of NB tumor cells is conserved upon metastasis and tumor cell type composition is NB subtype-dependent. NB cells signal to the BM microenvironment, rewiring via macrophage mgration inhibitory factor and midkine signaling specifically monocytes, which exhibit M1 and M2 features, are marked by activation of pro- and anti-inflammatory programs, and express tumor-promoting factors, reminiscent of tumor-associated macrophages. The interactions and pathways characterized in our study provide the basis for therapeutic approaches that target tumor-to-microenvironment interactions | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
700 | 1 | |a Esser-Skala, Wolfgang |e verfasserin |4 aut | |
700 | 1 | |a Dnyansagar, Rohit |e verfasserin |4 aut | |
700 | 1 | |a Sindelar, Samuel |e verfasserin |4 aut | |
700 | 1 | |a Rifatbegovic, Fikret |e verfasserin |4 aut | |
700 | 1 | |a Bileck, Andrea |e verfasserin |4 aut | |
700 | 1 | |a Skos, Lukas |e verfasserin |4 aut | |
700 | 1 | |a Bozsaky, Eva |e verfasserin |4 aut | |
700 | 1 | |a Lazic, Daria |e verfasserin |4 aut | |
700 | 1 | |a Shaw, Lisa |e verfasserin |4 aut | |
700 | 1 | |a Tötzl, Marcus |e verfasserin |4 aut | |
700 | 1 | |a Tarlungeanu, Dora |e verfasserin |4 aut | |
700 | 1 | |a Bernkopf, Marie |e verfasserin |4 aut | |
700 | 1 | |a Rados, Magdalena |e verfasserin |4 aut | |
700 | 1 | |a Weninger, Wolfgang |e verfasserin |4 aut | |
700 | 1 | |a Tomazou, Eleni M |e verfasserin |4 aut | |
700 | 1 | |a Bock, Christoph |e verfasserin |4 aut | |
700 | 1 | |a Gerner, Christopher |e verfasserin |4 aut | |
700 | 1 | |a Ladenstein, Ruth |e verfasserin |4 aut | |
700 | 1 | |a Farlik, Matthias |e verfasserin |4 aut | |
700 | 1 | |a Fortelny, Nikolaus |e verfasserin |4 aut | |
700 | 1 | |a Taschner-Mandl, Sabine |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 14(2023), 1 vom: 26. Juni, Seite 3620 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
773 | 1 | 8 | |g volume:14 |g year:2023 |g number:1 |g day:26 |g month:06 |g pages:3620 |
856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-023-39210-0 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 14 |j 2023 |e 1 |b 26 |c 06 |h 3620 |