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Artikel ; Online: Defining Gene Function in Spermatogonial Stem Cells Through Conditional Knockout Approaches.

Legrand, Julien M D / Hobbs, Robin M

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

2023 Band 2656, Seite(n) 261–307

Abstract: Mammalian male fertility is maintained throughout life by a population of self-renewing mitotic germ cells known as spermatogonial stem cells (SSCs). Much of our current understanding regarding the molecular mechanisms underlying SSC activity is derived ... ...

Abstract	Mammalian male fertility is maintained throughout life by a population of self-renewing mitotic germ cells known as spermatogonial stem cells (SSCs). Much of our current understanding regarding the molecular mechanisms underlying SSC activity is derived from studies using conditional knockout mouse models. Here, we provide a guide for the selection and use of mouse strains to develop conditional knockout models for the study of SSCs, as well as their precursors and differentiation-committed progeny. We describe Cre recombinase-expressing strains, breeding strategies to generate experimental groups, and treatment regimens for inducible knockout models and provide advice for verifying and improving conditional knockout efficiency. This resource can be beneficial to those aiming to develop conditional knockout models for the study of SSC development and postnatal function.
Mesh-Begriff(e)	Male ; Animals ; Mice ; Spermatogonia ; Mice, Knockout ; Stem Cells ; Cell Differentiation/genetics ; Adult Germline Stem Cells ; Spermatogenesis/genetics ; Testis ; Mammals
Sprache	Englisch
Erscheinungsdatum	2023-05-30
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3139-3_15
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Growth Factor and Cytokine Delivery Systems for Wound Healing.

Legrand, Julien M D / Martino, Mikaël M

Cold Spring Harbor perspectives in biology

2022 Band 14, Heft 8

Abstract: Skin wound healing is a highly coordinated process involving multiple tissue-resident and recruited cell types. Cells within the wound microenvironment respond to key secreted factors such as pro-proliferative growth factors and immunomodulatory ... ...

Abstract	Skin wound healing is a highly coordinated process involving multiple tissue-resident and recruited cell types. Cells within the wound microenvironment respond to key secreted factors such as pro-proliferative growth factors and immunomodulatory cytokines to repair the skin and promptly restore its essential barrier role. Therefore, recombinant growth factors and cytokines are promising therapeutics for skin wounds, in particular for large acute wounds such as burns, or wounds associated with underlying pathologies such as nonhealing chronic and diabetic wounds. However, translation of growth factors and cytokines into clinically effective treatments has been limited. Short half-life, poor stability, rapid diffusion, uncontrolled signaling, and systemic side effects are currently the key challenges to developing efficient growth factor- and cytokine-based therapies. To overcome these limitations, novel delivery systems have been developed to improve the regenerative potential of recombinant growth factors and cytokines. In this review, we discuss biomaterial and protein engineering strategies used to optimize the delivery of growth factor and cytokine therapeutics for skin wound treatment.
Mesh-Begriff(e)	Biocompatible Materials ; Cytokines ; Intercellular Signaling Peptides and Proteins ; Skin ; Wound Healing
Chemische Substanzen	Biocompatible Materials ; Cytokines ; Intercellular Signaling Peptides and Proteins
Sprache	Englisch
Erscheinungsdatum	2022-08-01
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ISSN	1943-0264
ISSN (online)	1943-0264
DOI	10.1101/cshperspect.a041234
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Impact of 10-Myr scale monsoon dynamics on Mesozoic climate and ecosystems.

Ikeda, Masayuki / Ozaki, Kazumi / Legrand, Julien

Scientific reports

2020 Band 10, Heft 1, Seite(n) 11984

Abstract: Earth's orbital variations on timescales of ... ...

Abstract	Earth's orbital variations on timescales of 10
Sprache	Englisch
Erscheinungsdatum	2020-07-23
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-68542-w
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: A superior extracellular matrix binding motif to enhance the regenerative activity and safety of therapeutic proteins.

Alshoubaki, Yasmin K / Lu, Yen-Zhen / Legrand, Julien M D / Karami, Rezvan / Fossat, Mathilde / Salimova, Ekaterina / Julier, Ziad / Martino, Mikaël M

NPJ Regenerative medicine

2023 Band 8, Heft 1, Seite(n) 25

Abstract: Among therapeutic proteins, cytokines and growth factors have great potential for regenerative medicine applications. However, these molecules have encountered limited clinical success due to low effectiveness and major safety concerns, highlighting the ... ...

Abstract	Among therapeutic proteins, cytokines and growth factors have great potential for regenerative medicine applications. However, these molecules have encountered limited clinical success due to low effectiveness and major safety concerns, highlighting the need to develop better approaches that increase efficacy and safety. Promising approaches leverage how the extracellular matrix (ECM) controls the activity of these molecules during tissue healing. Using a protein motif screening strategy, we discovered that amphiregulin possesses an exceptionally strong binding motif for ECM components. We used this motif to confer the pro-regenerative therapeutics platelet-derived growth factor-BB (PDGF-BB) and interleukin-1 receptor antagonist (IL-1Ra) a very high affinity to the ECM. In mouse models, the approach considerably extended tissue retention of the engineered therapeutics and reduced leakage in the circulation. Prolonged retention and minimal systemic diffusion of engineered PDGF-BB abolished the tumour growth-promoting adverse effect that was observed with wild-type PDGF-BB. Moreover, engineered PDGF-BB was substantially more effective at promoting diabetic wound healing and regeneration after volumetric muscle loss, compared to wild-type PDGF-BB. Finally, while local or systemic delivery of wild-type IL-1Ra showed minor effects, intramyocardial delivery of engineered IL-1Ra enhanced cardiac repair after myocardial infarction by limiting cardiomyocyte death and fibrosis. This engineering strategy highlights the key importance of exploiting interactions between ECM and therapeutic proteins for developing effective and safer regenerative therapies.
Sprache	Englisch
Erscheinungsdatum	2023-05-22
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	2057-3995
ISSN (online)	2057-3995
DOI	10.1038/s41536-023-00297-0
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Terrestrial and marine organic matter evidence from a Cretaceous deep-sea chert of Japan: Implications for enhanced hydrological cycle during the Aptian OAE 1a

Nakagawa, Yuki / Legrand, Julien / Bôle, Maximilien / Hori, Rie S. / Kuroda, Junichiro / Hasegawa, Hitoshi / Ikeda, Masayuki

Global and planetary change. 2022 Aug., v. 215

2022

Abstract: The early Aptian Oceanic Anoxic Event (OAE 1a; ca. 120 Ma) was accompanied by a massive eruption of the Ontong Java Plateau, doubling atmospheric pCO₂, and increasing sea surface temperature by 4–8 °C. In this study, we attempted a palynological analysis ...

Abstract	The early Aptian Oceanic Anoxic Event (OAE 1a; ca. 120 Ma) was accompanied by a massive eruption of the Ontong Java Plateau, doubling atmospheric pCO₂, and increasing sea surface temperature by 4–8 °C. In this study, we attempted a palynological analysis of the Hauterivian to Cenomanian deep–sea chert from the Goshikinohama site, and successfully obtained a variety of microremains, mainly represented by amorphous organic matter, aggregations of organic and inorganic particles, and cuticle fragments. One Hauterivian and many Aptian samples unexpectedly yielded terrestrial plant material, such as resins and wood fragments with tracheids, which represent the first record of terrestrial plant microremains from deep-sea pelagic chert. The occurrence of wood fragments within the negative and positive δ¹³C excursions during the OAE 1a can be correlated with an interval of increased atmospheric CO₂ level. We can also suggest that the occurrence of resins, mainly within the mudstone-rich chert intervals of the early Aptian negative δ¹³C peak and the middle-upper Aptian interval, are possibly related with periods with sea-level drops. Similar massive resin deposition events have been linked with intensified hydrological cycling during other abrupt climatic disruptions, such as the Carnian Pluvial Event, the Triassic−Jurassic boundary, and the Paleocene−Eocene Thermal Maximum. Therefore, an increase of terrestrial plant burial in deep–sea chert is likely linked with a massive plant discharge related with enhanced hydrological cycles, such as intensified storms and/or some sea–level change during the OAE 1a.
Schlagwörter	Aptian age ; Japan ; Paleogene period ; carbon dioxide ; hydrologic cycle ; organic matter ; palynology ; plants (botany) ; sea level ; surface water temperature ; tracheids ; wood
Sprache	Englisch
Erscheinungsverlauf	2022-08
Erscheinungsort	Elsevier B.V.
Dokumenttyp	Artikel
ZDB-ID	2016967-X
ISSN	0921-8181
ISSN	0921-8181
DOI	10.1016/j.gloplacha.2022.103886
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel ; Online: STIM2 is involved in the regulation of apoptosis and the cell cycle in normal and malignant monocytic cells.

Djordjevic, Stefan / Itzykson, Raphaël / Hague, Frédéric / Lebon, Delphine / Legrand, Julien / Ouled-Haddou, Hakim / Jedraszak, Guillaume / Harbonnier, Juliette / Collet, Louison / Paubelle, Etienne / Marolleau, Jean-Pierre / Garçon, Loïc / Boyer, Thomas

Molecular oncology

2024

Abstract: Calcium is a ubiquitous messenger that regulates a wide range of cellular functions, but its involvement in the pathophysiology of acute myeloid leukemia (AML) is not widely investigated. Here, we identified, from an analysis of The Cancer Genome Atlas ... ...

Abstract	Calcium is a ubiquitous messenger that regulates a wide range of cellular functions, but its involvement in the pathophysiology of acute myeloid leukemia (AML) is not widely investigated. Here, we identified, from an analysis of The Cancer Genome Atlas and genotype-tissue expression databases, stromal interaction molecule 2 (STIM2) as being highly expressed in AML with monocytic differentiation and negatively correlated with overall survival. This was confirmed on a validation cohort of 407 AML patients. We then investigated the role of STIM2 in cell proliferation, differentiation, and survival in two leukemic cell lines with monocytic potential and in normal hematopoietic stem cells. STIM2 expression increased at the RNA and protein levels upon monocyte differentiation. Phenotypically, STIM2 knockdown drastically inhibited cell proliferation and induced genomic stress with DNA double-strand breaks, as shown by increased levels of phosphorylate histone H2AXγ (p-H2AXγ), followed by activation of the cellular tumor antigen p53 pathway, decreased expression of cell cycle regulators such as cyclin-dependent kinase 1 (CDK1)-cyclin B1 and M-phase inducer phosphatase 3 (CDC25c), and a decreased apoptosis threshold with a low antiapoptotic/proapoptotic protein ratio. Our study reports STIM2 as a new actor regulating genomic stability and p53 response in terms of cell cycle and apoptosis of human normal and malignant monocytic cells.
Sprache	Englisch
Erscheinungsdatum	2024-01-17
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13584
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: RNA processing in the male germline: Mechanisms and implications for fertility.

Legrand, Julien M D / Hobbs, Robin M

Seminars in cell & developmental biology

2017 Band 79, Seite(n) 80–91

Abstract: Mammalian spermatogenesis is a tightly coordinated process that gives rise to mature spermatozoa capable of fertilising an ovum during sexual reproduction. A population of stem and progenitor cells known as undifferentiated spermatogonia enables ... ...

Abstract	Mammalian spermatogenesis is a tightly coordinated process that gives rise to mature spermatozoa capable of fertilising an ovum during sexual reproduction. A population of stem and progenitor cells known as undifferentiated spermatogonia enables continual spermatogenesis throughout life. A complex transcriptional network that balances self-renewal of spermatogonia with their timely differentiation in order to maintain constant fertility regulates this process. Importantly, post-transcriptional regulation of gene expression plays a critical role in spermatogenesis, necessitated by the profound genetic and morphological changes that occur during meiosis and sperm maturation. Pre-mRNA splicing, mRNA export, maintenance of transcript stability and translation are key RNA processing steps that are regulated in the male germline to maintain coordinated gene expression. In this review, we examine these processes in the context of mammalian spermatogenesis and provide an overview of key mediators at each step.
Mesh-Begriff(e)	Animals ; Cell Differentiation/genetics ; Fertility/genetics ; Humans ; Male ; RNA Precursors/genetics ; RNA Processing, Post-Transcriptional ; Spermatogenesis/genetics ; Spermatogonia/cytology ; Spermatogonia/metabolism ; Stem Cells/cytology ; Stem Cells/metabolism
Chemische Substanzen	RNA Precursors
Sprache	Englisch
Erscheinungsdatum	2017-10-20
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2017.10.006
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Engineering Strategy and Vector Library for the Rapid Generation of Modular Light-Controlled Protein-Protein Interactions.

Tichy, Alexandra-Madelaine / Gerrard, Elliot J / Legrand, Julien M D / Hobbs, Robin M / Janovjak, Harald

Journal of molecular biology

2019 Band 431, Heft 17, Seite(n) 3046–3055

Abstract: Optogenetics enables the spatio-temporally precise control of cell and animal behavior. Many optogenetic tools are driven by light-controlled protein-protein interactions (PPIs) that are repurposed from natural light-sensitive domains (LSDs). Applying ... ...

Abstract	Optogenetics enables the spatio-temporally precise control of cell and animal behavior. Many optogenetic tools are driven by light-controlled protein-protein interactions (PPIs) that are repurposed from natural light-sensitive domains (LSDs). Applying light-controlled PPIs to new target proteins is challenging because it is difficult to predict which of the many available LSDs, if any, will yield robust light regulation. As a consequence, fusion protein libraries need to be prepared and tested, but methods and platforms to facilitate this process are currently not available. Here, we developed a genetic engineering strategy and vector library for the rapid generation of light-controlled PPIs. The strategy permits fusing a target protein to multiple LSDs efficiently and in two orientations. The public and expandable library contains 29 vectors with blue, green or red light-responsive LSDs, many of which have been previously applied ex vivo and in vivo. We demonstrate the versatility of the approach and the necessity for sampling LSDs by generating light-activated caspase-9 (casp9) enzymes. Collectively, this work provides a new resource for optical regulation of a broad range of target proteins in cell and developmental biology.
Mesh-Begriff(e)	Animals ; Caspase 9/radiation effects ; Gene Library ; Genetic Engineering ; HEK293 Cells ; Humans ; Light ; Optogenetics/methods ; Protein Engineering/methods ; Protein Interaction Domains and Motifs/radiation effects
Chemische Substanzen	Caspase 9 (EC 3.4.22.-)
Sprache	Englisch
Erscheinungsdatum	2019-05-29
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2019.05.033
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Engineering Strategy and Vector Library for the Rapid Generation of Modular Light-Controlled Protein–Protein Interactions

Tichy, Alexandra-Madelaine / Gerrard, Elliot J / Legrand, Julien M.D / Hobbs, Robin M / Janovjak, Harald

Journal of molecular biology. 2019 Aug. 09, v. 431, no. 17

2019

Abstract: Optogenetics enables the spatio-temporally precise control of cell and animal behavior. Many optogenetic tools are driven by light-controlled protein–protein interactions (PPIs) that are repurposed from natural light-sensitive domains (LSDs). Applying ... ...

Abstract	Optogenetics enables the spatio-temporally precise control of cell and animal behavior. Many optogenetic tools are driven by light-controlled protein–protein interactions (PPIs) that are repurposed from natural light-sensitive domains (LSDs). Applying light-controlled PPIs to new target proteins is challenging because it is difficult to predict which of the many available LSDs, if any, will yield robust light regulation. As a consequence, fusion protein libraries need to be prepared and tested, but methods and platforms to facilitate this process are currently not available. Here, we developed a genetic engineering strategy and vector library for the rapid generation of light-controlled PPIs. The strategy permits fusing a target protein to multiple LSDs efficiently and in two orientations. The public and expandable library contains 29 vectors with blue, green or red light-responsive LSDs, many of which have been previously applied ex vivo and in vivo. We demonstrate the versatility of the approach and the necessity for sampling LSDs by generating light-activated caspase-9 (casp9) enzymes. Collectively, this work provides a new resource for optical regulation of a broad range of target proteins in cell and developmental biology.
Schlagwörter	animal behavior ; caspase-9 ; engineering ; genetic engineering ; optogenetics ; protein-protein interactions ; proteins
Sprache	Englisch
Erscheinungsverlauf	2019-0809
Umfang	p. 3046-3055.
Erscheinungsort	Elsevier Ltd
Dokumenttyp	Artikel
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2019.05.033
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel ; Online: Distinctive molecular features of regenerative stem cells in the damaged male germline.

La, Hue M / Liao, Jinyue / Legrand, Julien M D / Rossello, Fernando J / Chan, Ai-Leen / Vaghjiani, Vijesh / Cain, Jason E / Papa, Antonella / Lee, Tin Lap / Hobbs, Robin M

Nature communications

2022 Band 13, Heft 1, Seite(n) 2500

Abstract: Maintenance of male fertility requires spermatogonial stem cells (SSCs) that self-renew and generate differentiating germ cells for production of spermatozoa. Germline cells are sensitive to genotoxic drugs and patients receiving chemotherapy can become ... ...

Abstract	Maintenance of male fertility requires spermatogonial stem cells (SSCs) that self-renew and generate differentiating germ cells for production of spermatozoa. Germline cells are sensitive to genotoxic drugs and patients receiving chemotherapy can become infertile. SSCs surviving treatment mediate germline recovery but pathways driving SSC regenerative responses remain poorly understood. Using models of chemotherapy-induced germline damage and recovery, here we identify unique molecular features of regenerative SSCs and characterise changes in composition of the undifferentiated spermatogonial pool during germline recovery by single-cell analysis. Increased mitotic activity of SSCs mediating regeneration is accompanied by alterations in growth factor signalling including PI3K/AKT and mTORC1 pathways. While sustained mTORC1 signalling is detrimental for SSC maintenance, transient mTORC1 activation is critical for the regenerative response. Concerted inhibition of growth factor signalling disrupts core features of the regenerative state and limits germline recovery. We also demonstrate that the FOXM1 transcription factor is a target of growth factor signalling in undifferentiated spermatogonia and provide evidence for a role in regeneration. Our data confirm dynamic changes in SSC functional properties following damage and support an essential role for microenvironmental growth factors in promoting a regenerative state.
Mesh-Begriff(e)	Cell Differentiation/physiology ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Spermatogenesis/genetics ; Spermatogonia ; Stem Cells/metabolism ; Testis/metabolism
Chemische Substanzen	Intercellular Signaling Peptides and Proteins ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
Sprache	Englisch
Erscheinungsdatum	2022-05-06
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-30130-z
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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