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Article ; Online: Cell specification and functional interactions in the pig blastocyst inferred from single-cell transcriptomics and uterine fluids proteomics.

Dufour, Adrien / Kurylo, Cyril / Stöckl, Jan B / Laloë, Denis / Bailly, Yoann / Manceau, Patrick / Martins, Frédéric / Turhan, Ali G / Ferchaud, Stéphane / Pain, Bertrand / Fröhlich, Thomas / Foissac, Sylvain / Artus, Jérôme / Acloque, Hervé

Genomics

2024 Volume 116, Issue 2, Page(s) 110780

Abstract: The embryonic development of the pig comprises a long in utero pre- and peri-implantation development, which dramatically differs from mice and humans. During this peri-implantation period, a complex series of paracrine signals establishes an intimate ... ...

Abstract	The embryonic development of the pig comprises a long in utero pre- and peri-implantation development, which dramatically differs from mice and humans. During this peri-implantation period, a complex series of paracrine signals establishes an intimate dialogue between the embryo and the uterus. To better understand the biology of the pig blastocyst during this period, we generated a large dataset of single-cell RNAseq from early and hatched blastocysts, spheroid and ovoid conceptus and proteomic datasets from corresponding uterine fluids. Our results confirm the molecular specificity and functionality of the three main cell populations. We also discovered two previously unknown subpopulations of the trophectoderm, one characterised by the expression of LRP2, which could represent progenitor cells, and the other, expressing pro-apoptotic markers, which could correspond to the Rauber's layer. Our work provides new insights into the biology of these populations, their reciprocal functional interactions, and the molecular dialogue with the maternal uterine environment.
MeSH term(s)	Pregnancy ; Humans ; Female ; Swine ; Mice ; Animals ; Proteomics ; Blastocyst/metabolism ; Embryo Implantation/physiology ; Embryonic Development/genetics ; Gene Expression Profiling
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	356334-0
ISSN	1089-8646 ; 0888-7543
ISSN (online)	1089-8646
ISSN	0888-7543
DOI	10.1016/j.ygeno.2023.110780
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Article ; Online: Preimplantation development in ungulates: a 'ménage à quatre' scenario.

Artus, Jérôme / Hue, Isabelle / Acloque, Hervé

Reproduction (Cambridge, England)

2019 Volume 159, Issue 3, Page(s) R151–R172

Abstract: In ungulates, early embryonic development differs dramatically from that of mice and humans and is characterized by an extended period of pre- and peri-implantation development in utero. After hatching from the zona pellucida, the ungulate blastocyst ... ...

Abstract	In ungulates, early embryonic development differs dramatically from that of mice and humans and is characterized by an extended period of pre- and peri-implantation development in utero. After hatching from the zona pellucida, the ungulate blastocyst will stay free in the uterus for many days before implanting within the uterine wall. During this protracted peri-implantation period, an intimate dialog between the embryo and the uterus is established through a complex series of paracrine signals. The blastocyst elongates, leading to extreme growth of extra-embryonic tissues, and at the same time, the inner cell mass moves up into the trophoblast and evolves into the embryonic disc, which is directly exposed to molecules present in the uterine fluids. In the peri-implantation period, uterine glands secrete a wide range of molecules, including enzymes, growth factors, adhesion proteins, cytokines, hormones, and nutrients like amino and fatty acids, which are collectively referred to as histotroph. The identification, role, and effects of these secretions on the biology of the conceptus are still being described; however, the studies that have been conducted to date have demonstrated that histotroph is essential for embryonic development and serves a critical function during the pre- and peri implantation periods. Here, we present an overview of current knowledge on the molecular dialogue among embryonic, extraembryonic, and maternal tissues prior to implantation. Taken together, the body of work described here demonstrates the extent to which this dialog enables the coordination of the development of the conceptus with respect to the establishment of embryonic and extra-embryonic tissues as well as in preparation for implantation.
MeSH term(s)	Animals ; Artiodactyla/embryology ; Blastocyst/physiology ; Embryonic Development ; Female ; Perissodactyla/embryology ; Uterus/physiology
Language	English
Publishing date	2019-11-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2034501-X
ISSN	1741-7899 ; 1470-1626 ; 1476-3990
ISSN (online)	1741-7899
ISSN	1470-1626 ; 1476-3990
DOI	10.1530/REP-19-0348
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Article ; Online: A close look at the mammalian blastocyst: epiblast and primitive endoderm formation.

Artus, Jérôme / Chazaud, Claire

Cellular and molecular life sciences : CMLS

2014 Volume 71, Issue 17, Page(s) 3327–3338

Abstract: During early development, the mammalian embryo undergoes a series of profound changes that lead to the formation of two extraembryonic tissues--the trophectoderm and the primitive endoderm. These tissues encapsulate the pluripotent epiblast at the time ... ...

Abstract	During early development, the mammalian embryo undergoes a series of profound changes that lead to the formation of two extraembryonic tissues--the trophectoderm and the primitive endoderm. These tissues encapsulate the pluripotent epiblast at the time of implantation. The current model proposes that the formation of these lineages results from two consecutive binary cell fate decisions. The first controls the formation of the trophectoderm and the inner cell mass, and the second controls the formation of the primitive endoderm and the epiblast within the inner cell mass. While early mammalian embryos develop with extensive plasticity, the embryonic pattern prior to implantation is remarkably reproducible. Here, we review the molecular mechanisms driving the cell fate decision between primitive endoderm and epiblast in the mouse embryo and integrate data from recent studies into the current model of the molecular network regulating the segregation between these lineages and their subsequent differentiation.
MeSH term(s)	Animals ; Blastocyst/cytology ; Blastocyst/physiology ; Blastocyst Inner Cell Mass/cytology ; Blastocyst Inner Cell Mass/metabolism ; Blastomeres/physiology ; Cell Differentiation ; Cell Lineage ; Cell Movement ; Cells, Cultured ; Embryonic Stem Cells/cytology ; Endoderm/cytology ; Fetal Proteins/physiology ; GATA Transcription Factors/physiology ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/physiology ; Mammals/genetics ; Mice/embryology ; Morphogenesis ; Morula/cytology ; Morula/physiology ; Nanog Homeobox Protein ; Species Specificity
Chemical Substances	Fetal Proteins ; GATA Transcription Factors ; Homeodomain Proteins ; Nanog Homeobox Protein ; Nanog protein, mouse
Language	English
Publishing date	2014-05-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-014-1630-3
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Article ; Online: BCR-ABL promotes hematopoietic stem and progenitor cell formation in embryonic stem cells.

Artus, Jérôme / Zenych, Alina / Simanic, Isidora / Desterke, Christophe / Clay, Denis / Saïm, Sonia / Ijjeh, Yousef / de Souza, Lucas Eduardo Botelho / Coignard, Sabrina / Bennaceur-Griscelli, Annelise / Turhan, Ali G / Foudi, Adlen

Experimental hematology

2023 Volume 124, Page(s) 22–35.e3

Abstract: Generating hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) has been a long-lasting quest in the field of hematopoiesis. Previous studies suggested that enforced expression of BCR-ABL, the unique oncogenic driver of chronic myelogeneous ...

Abstract	Generating hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) has been a long-lasting quest in the field of hematopoiesis. Previous studies suggested that enforced expression of BCR-ABL, the unique oncogenic driver of chronic myelogeneous leukemia (CML), in embryonic stem cells (ESCs)-derived hematopoietic cells is sufficient to confer long-term in vivo repopulating potential. To precisely uncover the molecular events regulated by the tyrosine kinase activity of BCR-ABL1 (p210) during the course of hematopoietic differentiation, we engineered a Tet-ON inducible system to modulate its expression in murine ESCs (mESCs). We showed in unique site-directed knock-in ESC model that BCR-ABL expression tightly regulated by doxycycline (dox) controls the formation and the maintenance of immature hematopoietic progenitors. Interestingly, these progenitors can be expanded in vitro for several passages in the presence of dox. Our analysis of cell surface markers and transcriptome compared with wild-type fetal and adult HSCs unraveled a similar molecular signature. Long-term culture initiating cell (LTC-IC) assay confirmed their self-renewal capacities albeit with a differentiation bias toward erythroid and myeloid cells. Collectively, our novel Tet-ON system represents a unique in vitro model to shed lights on ESC-derived hematopoiesis, CML initiation, and maintenance.
MeSH term(s)	Mice ; Animals ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism ; Fusion Proteins, bcr-abl/genetics ; Fusion Proteins, bcr-abl/metabolism ; Hematopoietic Stem Cells/metabolism ; Cell Differentiation ; Embryonic Stem Cells/metabolism ; Doxycycline/pharmacology ; Doxycycline/metabolism
Chemical Substances	Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Doxycycline (N12000U13O)
Language	English
Publishing date	2023-06-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185107-x
ISSN	1873-2399 ; 0531-5573 ; 0301-472X
ISSN (online)	1873-2399
ISSN	0531-5573 ; 0301-472X
DOI	10.1016/j.exphem.2023.06.002
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Article: A close look at the mammalian blastocyst: epiblast and primitive endoderm formation

Artus, Jérôme / Chazaud, Claire

Cellular and molecular life sciences. 2014 Sept., v. 71, no. 17

2014

Abstract: During early development, the mammalian embryo undergoes a series of profound changes that lead to the formation of two extraembryonic tissues—the trophectoderm and the primitive endoderm. These tissues encapsulate the pluripotent epiblast at the time of ...

Abstract	During early development, the mammalian embryo undergoes a series of profound changes that lead to the formation of two extraembryonic tissues—the trophectoderm and the primitive endoderm. These tissues encapsulate the pluripotent epiblast at the time of implantation. The current model proposes that the formation of these lineages results from two consecutive binary cell fate decisions. The first controls the formation of the trophectoderm and the inner cell mass, and the second controls the formation of the primitive endoderm and the epiblast within the inner cell mass. While early mammalian embryos develop with extensive plasticity, the embryonic pattern prior to implantation is remarkably reproducible. Here, we review the molecular mechanisms driving the cell fate decision between primitive endoderm and epiblast in the mouse embryo and integrate data from recent studies into the current model of the molecular network regulating the segregation between these lineages and their subsequent differentiation.
Keywords	blastocyst ; early development ; embryogenesis ; mice ; models
Language	English
Dates of publication	2014-09
Size	p. 3327-3338.
Publishing place	Springer Basel
Document type	Article
Note	Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-014-1630-3
Database	NAL-Catalogue (AGRICOLA)

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Article: Evidence of Antitumor and Antimetastatic Potential of Induced Pluripotent Stem Cell-Based Vaccines in Cancer Immunotherapy.

Kishi, Masae / Asgarova, Afag / Desterke, Christophe / Chaker, Diana / Artus, Jérôme / Turhan, Ali G / Bennaceur-Griscelli, Annelise / Griscelli, Frank

Frontiers in medicine

2021 Volume 8, Page(s) 729018

Abstract: Cancer is maintained by the activity of a rare population of self-renewing "cancer stem cells" (CSCs), which are resistant to conventional therapies. CSCs over-express several proteins shared with induced pluripotent stem cells (iPSCs). We show here that ...

Abstract	Cancer is maintained by the activity of a rare population of self-renewing "cancer stem cells" (CSCs), which are resistant to conventional therapies. CSCs over-express several proteins shared with induced pluripotent stem cells (iPSCs). We show here that allogenic or autologous murine iPSCs, combined with a histone deacetylase inhibitor (HDACi), are able to elicit major anti-tumor responses in a highly aggressive triple-negative breast cancer, as a relevant cancer stemness model. This immunotherapy strategy was effective in preventing tumor establishment and efficiently targeted CSCs by inducing extensive modifications of the tumor microenvironment. The anti-tumoral effect was correlated with the generation of CD4+, CD8+ T cells, and CD44+ CD62L- CCR7low CD127low T-effector memory cells, and the reduction of CD4+ CD25+FoxP3+ Tregs, Arg1
Language	English
Publishing date	2021-12-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2021.729018
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Article ; Online: PDGF Signaling in Primitive Endoderm Cell Survival Is Mediated by PI3K-mTOR Through p53-Independent Mechanism.

Bessonnard, Sylvain / Vandormael-Pournin, Sandrine / Coqueran, Sabrina / Cohen-Tannoudji, Michel / Artus, Jérôme

Stem cells (Dayton, Ohio)

2019 Volume 37, Issue 7, Page(s) 888–898

Abstract: Receptor tyrosine kinase signaling pathways are key regulators for the formation of the primitive endoderm (PrE) and the epiblast (Epi) from the inner cell mass (ICM) of the mouse preimplantation embryo. Among them, FGF signaling is critical for PrE cell ...

Abstract	Receptor tyrosine kinase signaling pathways are key regulators for the formation of the primitive endoderm (PrE) and the epiblast (Epi) from the inner cell mass (ICM) of the mouse preimplantation embryo. Among them, FGF signaling is critical for PrE cell specification, whereas PDGF signaling is critical for the survival of committed PrE cells. Here, we investigated possible functional redundancies among FGF, PDGF, and KIT signaling and showed that only PDGF signaling is involved in PrE cell survival. In addition, we analyzed the effectors downstream of PDGFRα. Our results suggest that the role of PDGF signaling in PrE cell survival is mediated through PI3K-mTOR and independently from p53. Lastly, we uncovered a role for PI3K-mTOR signaling in the survival of Epi cells. Taken together, we propose that survival of ICM cell lineages relies on the regulation of PI3K-mTOR signaling through the regulation of multiple signaling pathways. Stem Cells 2019;37:888-898.
MeSH term(s)	Animals ; Blastocyst ; Blastocyst Inner Cell Mass/cytology ; Blastocyst Inner Cell Mass/metabolism ; Cell Lineage/genetics ; Cell Survival ; Endoderm/cytology ; Endoderm/growth & development ; Endoderm/metabolism ; Female ; Fibroblast Growth Factors/genetics ; Fibroblast Growth Factors/metabolism ; Gene Expression Regulation, Developmental ; Male ; Mice ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Platelet-Derived Growth Factor/genetics ; Platelet-Derived Growth Factor/metabolism ; Proto-Oncogene Proteins c-kit/genetics ; Proto-Oncogene Proteins c-kit/metabolism ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Kit protein, mouse ; Platelet-Derived Growth Factor ; Tumor Suppressor Protein p53 ; Fibroblast Growth Factors (62031-54-3) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; mTOR protein, mouse (EC 2.7.1.1) ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1) ; Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1)
Language	English
Publishing date	2019-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1002/stem.3008
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Article ; Online: miR-495-3p sensitizes BCR-ABL1-expressing leukemic cells to tyrosine kinase inhibitors by targeting multidrug resistance 1 gene in T315I mutated cells.

Rittavee, Yutthana / Artus, Jérôme / Desterke, Christophe / Simanic, Isidora / de Souza, Lucas Eduardo Botelho / Riccaldi, Sandra / Coignard, Sabrina / Ijjeh, Yousef / Hugues, Patricia / Bennaceur-Griscelli, Annelise / Turhan, Ali G / Foudi, Adlen

Experimental hematology

2022 Volume 118, Page(s) 40–52

Abstract: Chronic myeloid leukemia (CML) is a clonal hematopoietic malignancy driven by the BCR-ABL1 fusion oncoprotein. The development of tyrosine kinase inhibitors (TKIs) has deeply increased long-term survival of CML patients. Nonetheless, one patient out of ... ...

Abstract	Chronic myeloid leukemia (CML) is a clonal hematopoietic malignancy driven by the BCR-ABL1 fusion oncoprotein. The development of tyrosine kinase inhibitors (TKIs) has deeply increased long-term survival of CML patients. Nonetheless, one patient out of four will switch TKI off owing either to drug intolerance or resistance partly due to amplification or mutations of BCR-ABL1 oncogene and alteration in ATP-binding cassette (ABC) transporters. Increasing evidence suggests the involvement of the microRNA miR-495-3p in cancer-associated chemoresistance through multidrug resistance 1 (MDR1) gene, which encodes an ATP-dependent efflux pump. Our study aimed at investigating the potential role of miR-495-3p in CML TKI chemo-sensitivity and determining the underlying molecular circuitry involved. We first observed that miR-495-3p expression was lower in BCR-ABL1-expressing cellular models in vitro. Notably, loss-of-function experiments showed increased proliferation associated with a decreased number of nondividing cells (G0/G1) and resistance to Imatinib. Conversely, our data showed that miR-495-3p overexpression hindered leukemic cell growth and TKI resistance in Imatinib-resistant T315I-mutant cells, as well as drug efflux activity through MDR1 regulation. Further investigating the role of miR-495-3p in CML patients, we found that predicted miR-495-3p targets were upregulated in patients in blast crisis that were involved in protein phosphorylation and associated with the worst prognosis. Taken together, our results demonstrate that downregulation of miR-495-3p expression is important in the malignant phenotype of CML and TKI resistance mechanisms and could be a useful biomarker and a potential therapeutic target to eradicate CML.
MeSH term(s)	Humans ; Imatinib Mesylate/pharmacology ; Fusion Proteins, bcr-abl/genetics ; Fusion Proteins, bcr-abl/metabolism ; Tyrosine Kinase Inhibitors ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Drug Resistance, Multiple ; Adenosine Triphosphate
Chemical Substances	Imatinib Mesylate (8A1O1M485B) ; Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Tyrosine Kinase Inhibitors ; Protein Kinase Inhibitors ; MicroRNAs ; Adenosine Triphosphate (8L70Q75FXE) ; MIRN495 microRNA, human
Language	English
Publishing date	2022-12-17
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185107-x
ISSN	1873-2399 ; 0531-5573 ; 0301-472X
ISSN (online)	1873-2399
ISSN	0531-5573 ; 0301-472X
DOI	10.1016/j.exphem.2022.12.003
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Article ; Online: Troika of the mouse blastocyst: lineage segregation and stem cells.

Artus, Jerome / Hadjantonakis, Anna-Katerina

Current stem cell research & therapy

2011 Volume 7, Issue 1, Page(s) 78–91

Abstract: The initial period of mammalian embryonic development is primarily devoted to cell commitment to the pluripotent lineage, as well as to the formation of extraembryonic tissues essential for embryo survival in utero. This phase of development is also ... ...

Abstract	The initial period of mammalian embryonic development is primarily devoted to cell commitment to the pluripotent lineage, as well as to the formation of extraembryonic tissues essential for embryo survival in utero. This phase of development is also characterized by extensive morphological transitions. Cells within the preimplantation embryo exhibit extraordinary cell plasticity and adaptation in response to experimental manipulation, highlighting the use of a regulative developmental strategy rather than a predetermined one resulting from the non-uniform distribution of maternal information in the cytoplasm. Consequently, early mammalian development represents a useful model to study how the three primary cell lineages; the epiblast, primitive endoderm (also referred to as the hypoblast) and trophoblast, emerge from a totipotent single cell, the zygote. In this review, we will discuss how the isolation and genetic manipulation of murine stem cells representing each of these three lineages has contributed to our understanding of the molecular basis of early developmental events.
MeSH term(s)	Animals ; Blastocyst/physiology ; Cell Differentiation ; Cell Lineage ; Embryonic Development ; Endoderm/physiology ; Germ Layers/physiology ; Mice ; Pluripotent Stem Cells/physiology ; Trophoblasts/physiology
Language	English
Publishing date	2011-11-04
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2251937-3
ISSN	2212-3946 ; 1574-888X
ISSN (online)	2212-3946
ISSN	1574-888X
DOI	10.2174/157488812798483403
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Article ; Online: Generation of chimeras by aggregation of embryonic stem cells with diploid or tetraploid mouse embryos.

Artus, Jérôme / Hadjantonakis, Anna-Katerina

Methods in molecular biology (Clifton, N.J.)

2011 Volume 693, Page(s) 37–56

Abstract: From the hybrid creatures of the Greek and Egyptian mythologies, the concept of the chimera has evolved and, in modern day biology, refers to an organism comprises of at least two populations of genetically distinct cells. Mouse chimeras have proven an ... ...

Abstract	From the hybrid creatures of the Greek and Egyptian mythologies, the concept of the chimera has evolved and, in modern day biology, refers to an organism comprises of at least two populations of genetically distinct cells. Mouse chimeras have proven an invaluable tool for the generation of genetically modified strains. In addition, chimeras have been extensively used in developmental biology as a powerful tool to analyze the phenotype of specific mutations, to attribute function to gene products and to address the question of cell autonomy versus noncell autonomy of gene function. This chapter describes a simple and economical technique used to generate mouse chimeras by embryo aggregation. Multiple aggregation combinations are described each of which can be tailored to answer particular biological questions.
MeSH term(s)	Animals ; Chimera ; Diploidy ; Embryo, Mammalian/cytology ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Female ; Male ; Mice ; Tetraploidy
Language	English
Publishing date	2011
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-60761-974-1_3
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