Blossey, Ralf

Cleri, Fabrizio

Giordano, Stefano

Lagadec, Chann

Palla, Pier Luca

English

HAL Descartes

AGENT-BASED GENETIC MULTICELLULAR 3D MODELLING OF STEM-CELL SPHEROIDS(GENESPHERE)

Archive Ouverte en Sciences de l'Information et de la Communication

HAL Id: hal-02344423
https://hal.archives-ouvertes.fr/hal-02344423
Submitted on 4 Nov 2019
HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.
L’archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d’enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.
AGENT-BASED GENETIC MULTICELLULAR 3D
MODELLING OF STEM-CELL SPHEROIDS
(GENESPHERE)
Fabrizio Cleri, Chann Lagadec, Ralf Blossey, Pier Luca Palla, Stefano
Giordano
To cite this version:
Fabrizio Cleri, Chann Lagadec, Ralf Blossey, Pier Luca Palla, Stefano Giordano. AGENT-BASED
GENETIC MULTICELLULAR 3D MODELLING OF STEM-CELL SPHEROIDS (GENESPHERE).
4thInternational Conference on Physics & Biological Systems, 2018 October 22-24, CNRS campus,
Oct 2018, Gif-sur-Yvette, France. ￿hal-02344423￿
COULD	X-ray	IRRADIATED	BREAST-CANCER	CELLS		REPROGRAM	INTO	CANCER-STEM-CELLS	?	
AGENT-BASED	GENETIC	MULTICELLULAR	3D	MODELLING	OF	
STEM-CELL	SPHEROIDS	(GENESPHERE)	
	
Fabrizio	CLERI,	Department	of	Physics	and	IEMN	CNRS	UMR8520,	University	of	Lille	
Chann	LAGADEC,	Cell	PlasCcity	and	Cancer,	INSERM	U908,	Lille	
Ralf	BLOSSEY,	Structural	and	FuncConal	Glycobiology,	CNRS	UMR8576,	Lille	
Pier	Luca	PALLA,	Department	of	Physics	and	IEMN	CNRS	UMR8520,	University	of	Lille	
Stefano	GIORDANO,	Ecole	Centrale	de	Lille	and	IEMN	CNRS	UMR8520,	Lille	
GENESPHERE:	AN	AGENT-BASED	MODEL	 SOME		RECENT		RESULTS	
BIBLIOGRAPHY	
Lagadec	C,	Vlashi	E,	Della	Donna	L,	Pajonk	F,	Stem	Cells	30,	833	(2012)	
Tomezak	M,	Abbadie	C,	LarEgau	E,	Cleri	F,	J	Theor	Biol	389,	146	(2015)	
Bailleul-Dubois	J,	Bidan	N,	LeBourhis	X,	Lagadec	C,	Oncologie,	19,	77	(2017)	
Cleri	F,	Eur	Phys	J	E,	submiPed	-	biorkiv:	hPps://doi.org/10.1101/431163		
The	main	objecEve	of	GENESPHERE	is	to	produce	
a	model	capable	of	tesEng	the	hypothesis	of	
radiaNon-induced	breast	cancer	stem	cells.		
In	recent	experiments,	we	observed	CSC-speciﬁc	
markers	to	appear	in	irradiated	non-tumorigenic	
cells	(T47D,	MCF-7,	MDA-MB-231	and	SUM159-	
PT),	either	isolated,	or	in	presence	of	pre-
exisEng	breast-CSCs.	We	characterized	the	up-
regulaEon	of	about	10	diﬀerent	genes,	among	
which	key	elements	of	the	Notch	pathway;	it	
was	shown,	e.g.,	that	simultaneous	down-
regulaEon	of	Sox2	and	Nanog	signiﬁcantly	
reduced	the	generaEon	of	new	breast-CSCs,	
contrary	to	down-regulaEon	of	either	one	alone;	
also,	down-regulaEon	of	Notch	receptors	
reduced	the	ability	to	form	spheroids	and	
radiaEon-induced	reprogramming.	
Oxygen	distribuEon	in	a	
growing	spheroid	
Simpliﬁed	network	for	the	control	of	ATP/ADP		
(T/D)	raEo,	via	glucose-oxygen	consumpEon	rate	
Long-term	3D	spheroid	growth	ABM	simulaEon	
including	necrosis,	quiescence	and	cell	shedding	
[Exp.	data	from	Y.	Jiang	et	al.	Biophys.	J.	89,	3884	(2005)]		
Single-cell-based	modeling	of	periodic	glucose-
oxygen	supply	at	constant	ATP	consumpEon	rate	(µ).	
Black/red/blue=9/18/36	mM	[glucose]		
TentaEve	phenotypic	decision	algorithm	for	the	reprogramming,	dependent	of	the	genomic	dynamics	of	β-catenin	and	ERK.	
Depending	on	the	input	signals,	diﬀerent	outcomes	can	result:	homeostasis,	duplicaEon	of	normal	cells,	or	stem	
reprogramming	vs.	repopulaEon,	if	reprogramming	occurs	before	duplicaEon.	The	inhibiEon	and	overexpression	of	the	
diﬀerent	factors	result	from	the	soluEon	of	reacEon-diﬀusion	PDEs.	
The	Agent-Based	Model	describes	moEle	cells	in	a	3D	network	
of	Voronoi	polyhedra.	Each	cell-agent	has:	a	local	phase	clock;	
duplicaEon	with	geneEc	inheritance;	normal,	stem,	or	various	
cancer-cell	phenotype;	diﬀusion	of	oxygen,	nutrients,	or	other	
chemicals;	a	basic	version	of	the	glycolysis	cycle,	with	the	ATP	
demand	semng	the	level	of	glucose/oxygen	consumpEon.	Cells	
can	absorb	radiaEon/chemical	damage,	described	by	a	Markov	
chain,	with	individual	cell-repair	mechanisms.	
The	next	level	of	enrichment	of	the	model	is	the	inclusion	of	a	
cell	systemic	network,	with	a	whole	new	sets	of	cell	markers	
describing	acEvaEon/repression	of	diﬀerent	factors	that	could	
characterize	the	CSC	and	radiaEon-induced	CSC	populaEons,	by	
means	of	PDE-based	kineEc	modeling.		
Growth	of	3D	mulEcellular	spheroids	is	an	important	assay	in	CSC	studies	


https://hal.archives-ouvertes.fr/hal-02344423/document

AGENT-BASED GENETIC MULTICELLULAR 3D MODELLING OF STEM-CELL SPHEROIDS(GENESPHERE)

Abstract

Similar works

Full text

Available Versions

HAL Descartes

Archive Ouverte en Sciences de l'Information et de la Communication