Spatial Transcriptomics Reveals a Myeloma Cell Architecture with Dysfunctional T-Cell Distribution, Neutrophil Traps, and Inflammatory Signaling

转录组 失调家庭 多发性骨髓瘤 炎症 细胞 细胞生物学 计算生物学 生物 免疫学 癌症研究 基因 医学 基因表达 遗传学 临床心理学
作者
Laura Sudupe,Emma Muiños López,Ana López-Pérez,Amaia Vilas‐Zornoza,Sarai Sarvide,P. Ripalda,Paula Aguirre-Ruiz,Patxi San Martín-Úriz,Marta Larráyoz,Laura Álvarez-Gigli,Marta Abengózar,Itziar Cenzano,Miguel Cócera,Javier Ruiz,Ignacio Sancho,Azari Bantan,Aleksandra Kurowska,Jin Ye,Phillip T Newton,Bruno Paiva,Juan R. Rodriguez‐Madoz,Vincenzo Lagani,Jesper Tegnér,Borja Sáez,José A. Martínez-Climent,Isabel A. Calvo,David Gómez-Cabrero,Felipe Prósper
标识
DOI:10.1101/2024.07.03.601833
摘要

ABSTRACT The bone marrow (BM) is a complex tissue where spatial relationships influence cell behavior, signaling, and function. Consequently, understanding the whole dynamics of cellular interactions requires complementary spatial techniques that preserve and map the architecture of cell populations in situ . We successfully conducted spatial transcriptional profiling using Visium Spatial Gene Expression in formalin-fixed paraffin-embedded (FFPE) BM samples obtained from healthy and Multiple Myeloma (MM) mouse models and patients, addressing the technical challenges of applying spatial technology to long bone samples. A custom data-analysis framework that combines spatial with single-cell transcriptomic profiles identified both the BM cellular composition and the existing cell relations. This allowed us to visualize the spatial distribution of transcriptionally heterogeneous MM plasma cells (MM-PC). We spatially delineated transcriptional programs associated with MM, including NETosis and IL-17-driven inflammatory signaling, which were inversely correlated to malignant PC-enriched regions. Furthermore, a gradient of MM-PC density spatially correlated with a shift from effector-to-exhausted T cell phenotypes. The translational relevance of our findings was confirmed using FFPE BM biopsies from MM patients with varying levels of malignant PC infiltration. In summary, we provide the first spatial transcriptomics analysis applied to a mouse and human mineralized bone tissue and illustrate the BM cellular architecture of MM, revealing deregulated mechanisms underlying MM intercellular communication.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
高大绝义完成签到,获得积分10
1秒前
1秒前
啊娴仔发布了新的文献求助10
2秒前
韩soso完成签到,获得积分10
4秒前
企鹅完成签到,获得积分10
5秒前
曹兆完成签到,获得积分10
7秒前
9秒前
jinboyuan应助曹兆采纳,获得10
12秒前
aa完成签到,获得积分10
14秒前
快乐仙知发布了新的文献求助10
15秒前
CipherSage应助CornellRong采纳,获得200
15秒前
11完成签到,获得积分10
17秒前
风铃鸟完成签到,获得积分10
20秒前
fd163c完成签到,获得积分10
21秒前
21秒前
hsx发布了新的文献求助30
22秒前
哈牛完成签到 ,获得积分10
22秒前
Lucas应助温婉的翎采纳,获得10
23秒前
风铃鸟发布了新的文献求助10
23秒前
521完成签到,获得积分20
23秒前
future完成签到 ,获得积分10
28秒前
脾气暴躁的小兔完成签到,获得积分10
29秒前
慕青应助噜噜采纳,获得10
29秒前
乐观期待完成签到,获得积分10
32秒前
32秒前
34秒前
噜噜完成签到,获得积分10
35秒前
JJ发布了新的文献求助10
36秒前
SciGPT应助Charlie采纳,获得10
37秒前
所所应助jenny_shjn采纳,获得10
38秒前
噜噜发布了新的文献求助10
40秒前
41秒前
fyjlfy完成签到 ,获得积分10
42秒前
勿明应助刀锋采纳,获得50
47秒前
48秒前
大气金毛完成签到 ,获得积分10
49秒前
huahua发布了新的文献求助10
54秒前
Limerencia完成签到,获得积分10
54秒前
考拉发布了新的文献求助10
55秒前
Linden_bd完成签到 ,获得积分10
55秒前
高分求助中
The Mother of All Tableaux Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 2400
Ophthalmic Equipment Market by Devices(surgical: vitreorentinal,IOLs,OVDs,contact lens,RGP lens,backflush,diagnostic&monitoring:OCT,actorefractor,keratometer,tonometer,ophthalmoscpe,OVD), End User,Buying Criteria-Global Forecast to2029 2000
Optimal Transport: A Comprehensive Introduction to Modeling, Analysis, Simulation, Applications 800
Official Methods of Analysis of AOAC INTERNATIONAL 600
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 588
T/CIET 1202-2025 可吸收再生氧化纤维素止血材料 500
Interpretation of Mass Spectra, Fourth Edition 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3950988
求助须知:如何正确求助?哪些是违规求助? 3496397
关于积分的说明 11081817
捐赠科研通 3226886
什么是DOI,文献DOI怎么找? 1784005
邀请新用户注册赠送积分活动 868114
科研通“疑难数据库(出版商)”最低求助积分说明 800997