Dataset Information

RNA-seq of primary human M2-polarized macrophages cultured in either high-concentration or low-concentration type I collagen.

ABSTRACT: M2-polarized macrophages have been shown to adapt their migration mode to physical properties of the surrounding extracellular matrix. They migrate in the integrin-mediated adhesion and proteolytic activity-dependent mesenchymal mode in stiff matrices, and in the integrin- and protease-independent amoeboid mode in low density, porous environments. To find out what impact has the switching between the migration modes on expression of both protein-coding and non-coding genes we employed RNA sequencing of total RNA depleted of ribosomal RNA isolated from M2 macrophages migrating in three-dimensional collagen gels of high or low concentration for 48 hours.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

DISEASE(S): Normal

SUBMITTER: Vladimír Čermák Jan Brábek

PROVIDER: E-MTAB-6643 | ArrayExpress | 2018-07-04

SECONDARY ACCESSION(S): ERP107802

REPOSITORIES: ArrayExpress, ENA

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Dataset's files

Source:

			Action	DRS
	E-MTAB-6643.idf.txt	Idf
	E-MTAB-6643.idf.txt_original	Idf
	E-MTAB-6643.processed.1.zip	Processed
	E-MTAB-6643.sdrf.txt	Txt

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Publications

RNA-seq of macrophages of amoeboid or mesenchymal migratory phenotype due to specific structure of environment.

Čermák Vladimír V Gandalovičová Aneta A Merta Ladislav L Fučíková Jitka J Špíšek Radek R Rösel Daniel D Brábek Jan J

Scientific data 20181002

M2-polarized macrophages have been shown to adapt their 3D migration mode to physical properties of surrounding extracellular matrix. They migrate in the integrin-mediated adhesion and proteolytic activity-dependent "mesenchymal" mode in stiff matrices and in the integrin and protease-independent "amoeboid" mode in low density, porous environments. To find out what impact the switching between the migration modes has on expression of both protein-coding and non-coding genes we employed RNA seque ...[more]

PMID: 30277482

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Project description:Recent technical advances have broadened our understanding of processes that govern mammalian cell migration in health and disease but many of the molecular and morphological alterations that precede and accompany movement of cells - in particular in three-dimensional (3D) environments - are still incompletely understood. In this manuscript, using high-resolution and time-lapse microscopy imaging approaches, we describe morphodynamic processes during rounded/amoeboid cell invasion and molecules associated with the cellular invasion structures. We used macrophages infected with the intracellular protozoan parasite Theileria annulata, which causes Tropical Theileriosis in susceptible ruminants such as domestic cattle. T. annulata transforms its host cell that, as a result, acquires many characteristics of human cancer cells including a markedly increased potential to migrate, disseminate and expand in the body of the host animal. Hence, virulence of the disease is associated with the capability of infected cells to disseminate inside the host. Using T. annulata-transformed macrophages as a model system, we described a novel mode of rounded/amoeboid macrophage migration. We show that filopodia-like membrane extensions at the leading edge lead the way and further evolve in blebbing membrane protrusions to promote progressive expansion of the matrix. Associated with focal invasion structures we detected ezrin, radixin, moesin-family proteins and their regulatory kinase MAP4K4. Furthermore, we linked Rho-kinase activity to contractile force generation, which is essential for infected cell motility. Thus, the motility mode of these parasite-transformed macrophages contrasts with those described so far in human macrophages such as the tunneling or mesenchymal modes, which require engulfment, compaction and ingestion of matrix or proteolytic matrix degradation, respectively. Together, our data reveal protrusion dynamics at the leading edge of invading cells in 3D at unprecedented temporal and spatial resolution and suggest a novel mode of rounded/amoeboid invasive cell motility that exploits actin-driven filopodia formation in combination with pressure-driven membrane blebs.