65 research outputs found
Kashiwara-Vergne solutions degree by degree
We show that solutions to the Kashiwara-Vergne problem can be extended degree
by degree. This can be used to simplify the computation of a class of Drinfel'd
associators, which under the Alekseev-Torossian conjecture, may comprise all
associators. We also give a proof that the associated graded Lie algebra of the
Kashiwara-Vergne group is isomorphic to the graded Kashiwara-Vergne Lie
algebra.Comment: 15 page
Electrochemically switchable platform for the micro-patterning and release of heterotypic cell sheets
This article describes a dynamic platform in which the biointerfacial properties of micro-patterned domains can be switched electrochemically through the spatio-temporally controlled dissolution and adsorption of polyelectrolyte coatings. Insulating SU-8 micro-patterns created on a transparent indium tin oxide electrode by photolithography allowed for the local control over the electrochemical dissolution of polyelectrolyte mono- and multilayers, with polyelectrolytes shielded from the electrochemical treatment by the underlying photoresist stencil. The platform allowed for the creation of micro-patterned cell co-cultures through the electrochemical removal of a non-fouling polyelectrolyte coating and the localized adsorption of a cell adhesive one after attachment of the first cell population. In addition, the use of weak adhesive polyelectrolyte coatings on the photoresist domains allowed for the detachment of a contiguous heterotypic cell sheet upon electrochemical trigger. Cells grown on the ITO domains peeled off upon electrochemical dissolution of the sacrificial polyelectrolyte substrate, whereas adjacent cell areas on the insulated weakly adhesive substrate easily detached through the contractile force generated by neighboring cells. This electrochemical strategy for the micro-patterning and detachment of heterotypic cell sheets combines simplicity, precision and versatility, and presents great prospects for the creation of cellular constructs which mimic the cellular complexity of native tissue
Cell cycle features of primate embryonic stem cells.
International audienceUsing flow cytometry measurements combined with quantitative analysis of cell cycle kinetics, we show that rhesus monkey embryonic stem cells (ESCs) are characterized by an extremely rapid transit through the G1 phase, which accounts for 15% of the total cell cycle duration. Monkey ESCs exhibit a non-phasic expression of cyclin E, which is detected during all phases of the cell cycle, and do not growth-arrest in G1 after gamma-irradiation, reflecting the absence of a G1 checkpoint. Serum deprivation or pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) did not result in any alteration in the cell cycle distribution, indicating that ESC growth does not rely on mitogenic signals transduced by the Ras/Raf/MEK pathway. Taken together, these data indicate that rhesus monkey ESCs, like their murine counterparts, exhibit unusual cell cycle features in which cell cycle control mechanisms operating during the G1 phase are reduced or absent
Apoptosis, G1 Phase Stall, and Premature Differentiation Account for Low Chimeric Competence of Human and Rhesus Monkey Naive Pluripotent Stem Cells
After reprogramming to naive pluripotency, human pluripotent stem cells (PSCs) still exhibit very low ability to make interspecies chimeras. Whether this is because they are inherently devoid of the attributes of chimeric competency or because naive PSCs cannot colonize embryos from distant species remains to be elucidated. Here, we have used different types of mouse, human, and rhesus monkey naive PSCs and analyzed their ability to colonize rabbit and cynomolgus monkey embryos. Mouse embryonic stem cells (ESCs) remained mitotically active and efficiently colonized host embryos. In contrast, primate naive PSCs colonized host embryos with much lower efficiency. Unlike mouse ESCs, they slowed DNA replication after dissociation and, after injection into host embryos, they stalled in the G1 phase and differentiated prematurely, regardless of host species. We conclude that human and non-human primate naive PSCs do not efficiently make chimeras because they are inherently unfit to remain mitotically active during colonization
Masses, radii, and orbits of small Kepler planets : The transition from gaseous to rocky planets
We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R â. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O).Peer reviewedFinal Accepted Versio
Masses, radii, and orbits of small Kepler planets: the transition from gaseous to rocky planets
We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R â. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O)
Probing transcriptional specificities and fate potential of postnatal neural progenitors in the mouse forebrain
Lors du dĂ©veloppement, la coordination dâĂ©vĂšnements molĂ©culaires et cellulaires mĂšne Ă la production du cortex qui orchestre les fonctions sensori-motrices et cognitives. Son dĂ©veloppement sâeffectue par Ă©tapes : les cellules gliales radiaires (RGs) â les cellules souches neurales (NSCs) du cerveau en dĂ©veloppement â et les cellules progĂ©nitrices de la zone ventriculaire (VZ) et de la zone sous ventriculaire (SVZ) gĂ©nĂšrent sĂ©quentiellement des vagues distinctes de nouveaux neurones qui formeront les diffĂ©rentes couches corticales. Autour de la naissance, les RGs changent de devenir et produisent des cellules gliales. Cependant, une fraction persiste tout au long de la vie dans la SVZ qui borde le ventricule, perdant au passage leur morphologie radiale. Ces NSCs produisent ensuite les diffĂ©rents sous types dâinterneurones du bulbe olfactif ainsi que des cellules gliales en fonction de leur origine spatiale dans la SVZ. Ces observations soulĂšvent dâimportantes questions non rĂ©solues sur 1) le codage transcriptionnel rĂ©gulant la rĂ©gionalisation de la SVZ, 2) le potentiel des NSCs postnatales dans la rĂ©paration cĂ©rĂ©brale, et 3) le lignage et les spĂ©cificitĂ©s transcriptionnelles entre les NSCs et leur descendants. Mon travail de doctorat repose sur une Ă©tude transcriptionnelle des domaines de la SVZ postnatale. Celle-ci soulignait le fort degrĂ© dâhĂ©tĂ©rogĂ©nĂ©itĂ© des NSCs et progĂ©niteurs et identifiait des rĂ©gulateurs transcriptionnels clĂ©s soutenant la rĂ©gionalisation. Jâai dĂ©veloppĂ© des approches bio-informatiques pour explorer ces donnĂ©es et connecter lâexpression de facteurs de transcription (TFs) avec la genĂšse rĂ©gionale de lignages neuraux distincts. Jâai ensuite dĂ©veloppĂ© un modĂšle dâablation ciblĂ©e pour Ă©tudier le potentiel rĂ©gĂ©nĂ©ratif des progĂ©niteurs postnataux dans divers contextes. Finalement, jâai participĂ© au dĂ©veloppement dâune procĂ©dure pour explorer et comparer des progĂ©niteurs prĂ© et postnataux Ă lâĂ©chelle de la cellule unique. Objectif 1 : Des expĂ©riences de transcriptomique et de cartographie ont Ă©tĂ© rĂ©alisĂ©es pour Ă©tudier la relation entre lâexpression rĂ©gionale de TFs par les NSCs et lâacquisition de leur devenir. Nos rĂ©sultats suggĂšrent un engagement prĂ©coce des NSCs Ă produire des types cellulaires dĂ©finis selon leur localisation spatiale dans la SVZ et identifient HOPX comme un marqueur dâune sous population biaisĂ© Ă gĂ©nĂ©rer des astrocytes. Objectif 2 : Jâai mis au point un modĂšle de lĂ©sion corticale qui permet lâablation ciblĂ©e de neurones de couches corticales dĂ©finies pour Ă©tudier la capacitĂ© rĂ©gĂ©nĂ©rative et la spĂ©cification appropriĂ©e des progĂ©niteurs postnataux. Une analyse quantitative des rĂ©gions adjacentes, incluant la rĂ©gion dorsale de la SVZ, a rĂ©vĂ©lĂ© une rĂ©ponse transitoire de progĂ©niteurs dĂ©finis. Objectif 3 : Nous avons dĂ©veloppĂ© la lignĂ©e de souris transgĂ©nique Neurog2CreERT2Ai14, qui permet le marquage de cohortes de progĂ©niteurs glutamatergiques et de leurs descendants. Nous avons montrĂ© quâune large fraction de ces progĂ©niteurs persiste dans le cerveau postnatal aprĂšs la fermeture de neurogĂ©nĂšse corticale. Ils ne sâaccumulent pas pendant le dĂ©veloppement embryonnaire mais sont produits par des RGs qui persistent aprĂšs la naissance dans la SVZ et qui continuent de gĂ©nĂ©rer des neurones corticaux, bien que lâefficacitĂ© soit faible. Le sĂ©quençage dâARN sur cellule unique a rĂ©vĂ©lĂ© une dĂ©rĂ©gulation transcriptionnelle qui corrĂšle avec le dĂ©clin progressif observĂ© in vivo de la neurogĂ©nĂšse corticale. Ensemble, ces rĂ©sultats soulignent le potentiel des Ă©tudes transcriptomiques Ă rĂ©soudre mais aussi Ă soulever des questions fondamentales comme les changements trancriptionnels intervenant dans une population de progĂ©niteurs au cours du temps et participant aux changements de leur destinĂ©e. Cette connaissance sera la clĂ© du dĂ©veloppement dâapproches novatrices pour recruter et promouvoir la gĂ©nĂ©ration de types cellulaires spĂ©cifiques, incluant les sous-types neuronaux dans un contexte pathologique.During development, a remarkable coordination of molecular and cellular events leads to the generation of the cortex, which orchestrates most sensorimotor and cognitive functions. Cortex development occurs in a stepwise manner: radial glia cells (RGs) - the neural stem cells (NSCs) of the developing brain - and progenitor cells from the ventricular zone (VZ) and the subventricular zone (SVZ) sequentially give rise to distinct waves of nascent neurons that form cortical layers in an inside-out manner. Around birth, RGs switch fate to produce glial cells. A fraction of neurogenic RGs that lose their radial morphology however persists throughout postnatal life in the subventricular zone that lines the lateral ventricles. These NSCs give rise to different subtypes of olfactory bulb interneurons and glial cells, according to their spatial origin and location within the postnatal SVZ. These observations raise important unresolved questions on 1) the transcriptional coding of postnatal SVZ regionalization, 2) the potential of postnatal NSCs for cellular regeneration and forebrain repair, and 3) the lineage relationship and transcriptional specificities of postnatal NSCs and of their progenies. My PhD work built upon a previously published comparative transcriptional study of defined microdomains of the postnatal SVZ. This study highlighted a high degree of transcriptional heterogeneity within NSCs and progenitors and revealed transcriptional regulators as major hallmarks sustaining postnatal SVZ regionalization. I developed bioinformatics approaches to explore these datasets further and relate expression of defined transcription factors (TFs) to the regional generation of distinct neural lineages. I then developed a model of targeted ablation that can be used to investigate the regenerative potential of postnatal progenitors in various contexts. Finally, I participated to the development of a pipeline for exploring and comparing select populations of pre- and postnatal progenitors at the single cell level. Objective 1: Transcriptomic as well as fate mapping were used to investigate the relationship between regional expression of TFs by NSCs and their acquisition of distinct neural lineage fates. Our results supported an early priming of NSCs to produce defined cell types depending of their spatial location in the SVZ and identified HOPX as a marker of a subpopulation biased to generate astrocytes. Objective 2: I established a cortical lesion model, which allowed the targeted ablation of neurons of defined cortical layers to investigate the regenerative capacity and appropriate specification of postnatal cortical progenitors. Quantitative assessment of surrounding brain regions, including the dorsal SVZ, revealed a transient response of defined progenitor populations. Objective 3: We developed a transgenic mouse line, i.e. Neurog2CreERT2Ai14, which allowed the conditional labeling of birth-dated cohorts of glutamatergic progenitors and their progeny. We used fate-mapping approaches to show that a large fraction of Glu progenitors persist in the postnatal forebrain after closure of the cortical neurogenesis period. Postnatal Glu progenitors do not accumulate during embryonal development but are produced by embryonal RGs that persist after birth in the dorsal SVZ and continue to give rise to cortical neurons, although with low efficiency. Single-cell RNA sequencing revealed a dysregulation of transcriptional programs, which correlates with the gradual decline in cortical neurogenesis observed in vivo. Altogether, these data highlight the potential of transcriptomic studies to unravel but also to approach fundamental questions such as transcriptional changes occurring in a population of progenitors over time and participating to changes in their fate potential. This knowledge will be key in developing innovative approaches to recruit and promote the generation of selected cell types, including neuronal subtypes in pathologies
Etude des spécificités transcriptionnelles et de la compétence des progéniteurs neuraux postnataux du cerveau antérieur chez la souris
During development, a remarkable coordination of molecular and cellular events leads to the generation of the cortex, which orchestrates most sensorimotor and cognitive functions. Cortex development occurs in a stepwise manner: radial glia cells (RGs) - the neural stem cells (NSCs) of the developing brain - and progenitor cells from the ventricular zone (VZ) and the subventricular zone (SVZ) sequentially give rise to distinct waves of nascent neurons that form cortical layers in an inside-out manner. Around birth, RGs switch fate to produce glial cells. A fraction of neurogenic RGs that lose their radial morphology however persists throughout postnatal life in the subventricular zone that lines the lateral ventricles. These NSCs give rise to different subtypes of olfactory bulb interneurons and glial cells, according to their spatial origin and location within the postnatal SVZ. These observations raise important unresolved questions on 1) the transcriptional coding of postnatal SVZ regionalization, 2) the potential of postnatal NSCs for cellular regeneration and forebrain repair, and 3) the lineage relationship and transcriptional specificities of postnatal NSCs and of their progenies. My PhD work built upon a previously published comparative transcriptional study of defined microdomains of the postnatal SVZ. This study highlighted a high degree of transcriptional heterogeneity within NSCs and progenitors and revealed transcriptional regulators as major hallmarks sustaining postnatal SVZ regionalization. I developed bioinformatics approaches to explore these datasets further and relate expression of defined transcription factors (TFs) to the regional generation of distinct neural lineages. I then developed a model of targeted ablation that can be used to investigate the regenerative potential of postnatal progenitors in various contexts. Finally, I participated to the development of a pipeline for exploring and comparing select populations of pre- and postnatal progenitors at the single cell level. Objective 1: Transcriptomic as well as fate mapping were used to investigate the relationship between regional expression of TFs by NSCs and their acquisition of distinct neural lineage fates. Our results supported an early priming of NSCs to produce defined cell types depending of their spatial location in the SVZ and identified HOPX as a marker of a subpopulation biased to generate astrocytes. Objective 2: I established a cortical lesion model, which allowed the targeted ablation of neurons of defined cortical layers to investigate the regenerative capacity and appropriate specification of postnatal cortical progenitors. Quantitative assessment of surrounding brain regions, including the dorsal SVZ, revealed a transient response of defined progenitor populations. Objective 3: We developed a transgenic mouse line, i.e. Neurog2CreERT2Ai14, which allowed the conditional labeling of birth-dated cohorts of glutamatergic progenitors and their progeny. We used fate-mapping approaches to show that a large fraction of Glu progenitors persist in the postnatal forebrain after closure of the cortical neurogenesis period. Postnatal Glu progenitors do not accumulate during embryonal development but are produced by embryonal RGs that persist after birth in the dorsal SVZ and continue to give rise to cortical neurons, although with low efficiency. Single-cell RNA sequencing revealed a dysregulation of transcriptional programs, which correlates with the gradual decline in cortical neurogenesis observed in vivo. Altogether, these data highlight the potential of transcriptomic studies to unravel but also to approach fundamental questions such as transcriptional changes occurring in a population of progenitors over time and participating to changes in their fate potential. This knowledge will be key in developing innovative approaches to recruit and promote the generation of selected cell types, including neuronal subtypes in pathologies.Lors du dĂ©veloppement, la coordination dâĂ©vĂšnements molĂ©culaires et cellulaires mĂšne Ă la production du cortex qui orchestre les fonctions sensori-motrices et cognitives. Son dĂ©veloppement sâeffectue par Ă©tapes : les cellules gliales radiaires (RGs) â les cellules souches neurales (NSCs) du cerveau en dĂ©veloppement â et les cellules progĂ©nitrices de la zone ventriculaire (VZ) et de la zone sous ventriculaire (SVZ) gĂ©nĂšrent sĂ©quentiellement des vagues distinctes de nouveaux neurones qui formeront les diffĂ©rentes couches corticales. Autour de la naissance, les RGs changent de devenir et produisent des cellules gliales. Cependant, une fraction persiste tout au long de la vie dans la SVZ qui borde le ventricule, perdant au passage leur morphologie radiale. Ces NSCs produisent ensuite les diffĂ©rents sous types dâinterneurones du bulbe olfactif ainsi que des cellules gliales en fonction de leur origine spatiale dans la SVZ. Ces observations soulĂšvent dâimportantes questions non rĂ©solues sur 1) le codage transcriptionnel rĂ©gulant la rĂ©gionalisation de la SVZ, 2) le potentiel des NSCs postnatales dans la rĂ©paration cĂ©rĂ©brale, et 3) le lignage et les spĂ©cificitĂ©s transcriptionnelles entre les NSCs et leur descendants. Mon travail de doctorat repose sur une Ă©tude transcriptionnelle des domaines de la SVZ postnatale. Celle-ci soulignait le fort degrĂ© dâhĂ©tĂ©rogĂ©nĂ©itĂ© des NSCs et progĂ©niteurs et identifiait des rĂ©gulateurs transcriptionnels clĂ©s soutenant la rĂ©gionalisation. Jâai dĂ©veloppĂ© des approches bio-informatiques pour explorer ces donnĂ©es et connecter lâexpression de facteurs de transcription (TFs) avec la genĂšse rĂ©gionale de lignages neuraux distincts. Jâai ensuite dĂ©veloppĂ© un modĂšle dâablation ciblĂ©e pour Ă©tudier le potentiel rĂ©gĂ©nĂ©ratif des progĂ©niteurs postnataux dans divers contextes. Finalement, jâai participĂ© au dĂ©veloppement dâune procĂ©dure pour explorer et comparer des progĂ©niteurs prĂ© et postnataux Ă lâĂ©chelle de la cellule unique. Objectif 1 : Des expĂ©riences de transcriptomique et de cartographie ont Ă©tĂ© rĂ©alisĂ©es pour Ă©tudier la relation entre lâexpression rĂ©gionale de TFs par les NSCs et lâacquisition de leur devenir. Nos rĂ©sultats suggĂšrent un engagement prĂ©coce des NSCs Ă produire des types cellulaires dĂ©finis selon leur localisation spatiale dans la SVZ et identifient HOPX comme un marqueur dâune sous population biaisĂ© Ă gĂ©nĂ©rer des astrocytes. Objectif 2 : Jâai mis au point un modĂšle de lĂ©sion corticale qui permet lâablation ciblĂ©e de neurones de couches corticales dĂ©finies pour Ă©tudier la capacitĂ© rĂ©gĂ©nĂ©rative et la spĂ©cification appropriĂ©e des progĂ©niteurs postnataux. Une analyse quantitative des rĂ©gions adjacentes, incluant la rĂ©gion dorsale de la SVZ, a rĂ©vĂ©lĂ© une rĂ©ponse transitoire de progĂ©niteurs dĂ©finis. Objectif 3 : Nous avons dĂ©veloppĂ© la lignĂ©e de souris transgĂ©nique Neurog2CreERT2Ai14, qui permet le marquage de cohortes de progĂ©niteurs glutamatergiques et de leurs descendants. Nous avons montrĂ© quâune large fraction de ces progĂ©niteurs persiste dans le cerveau postnatal aprĂšs la fermeture de neurogĂ©nĂšse corticale. Ils ne sâaccumulent pas pendant le dĂ©veloppement embryonnaire mais sont produits par des RGs qui persistent aprĂšs la naissance dans la SVZ et qui continuent de gĂ©nĂ©rer des neurones corticaux, bien que lâefficacitĂ© soit faible. Le sĂ©quençage dâARN sur cellule unique a rĂ©vĂ©lĂ© une dĂ©rĂ©gulation transcriptionnelle qui corrĂšle avec le dĂ©clin progressif observĂ© in vivo de la neurogĂ©nĂšse corticale. Ensemble, ces rĂ©sultats soulignent le potentiel des Ă©tudes transcriptomiques Ă rĂ©soudre mais aussi Ă soulever des questions fondamentales comme les changements trancriptionnels intervenant dans une population de progĂ©niteurs au cours du temps et participant aux changements de leur destinĂ©e. Cette connaissance sera la clĂ© du dĂ©veloppement dâapproches novatrices pour recruter et promouvoir la gĂ©nĂ©ration de types cellulaires spĂ©cifiques, incluant les sous-types neuronaux dans un contexte pathologique
Influence des morphogÚnes sur la régionalisation de la zone sous-ventriculaire postnatale
Electrochemically switchable platform for the micro-patterning and release of heterotypic cell sheets
ISSN:1387-2176ISSN:1572-878
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