Alexandra Chicheportiche

CEA Paris-Saclay - Etablissement de Fontenay-aux-roses

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François D. Boussin

Université Paris Cité

Mathieu Daynac

Université Paris Cité

Marc‐André Mouthon

CEA Paris-Saclay - Etablissement de Fontenay-aux-roses

Jacqueline Bernardino-Sgherri

Commissariat à l'Énergie Atomique et aux Énergies Alternatives

Véronique Ménard

Inserm

Sébastien Couillard‐Després

Austrian Cluster for Tissue Regeneration

Christophe Antoniewski

Sorbonne Université

Corentin Bernou

Commissariat à l'Énergie Atomique et aux Énergies Alternatives

Benjamin Demaille

Inserm

Léa Bellenger

Inserm

Cooperative Institutions

Inserm

Commissariat à l'Énergie Atomique et aux Énergies Alternatives

CEA Paris-Saclay - Etablissement de Fontenay-aux-roses

Université Paris Cité

Centre National de la Recherche Scientifique

Université Paris-Saclay

CEA Paris-Saclay

Institut de Radiobiologie Cellulaire et Moléculaire

Jackson Laboratory

Paracelsus Medical University

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Author Index Vol. 105, 2004

Cytogenetic and Genome Research (2004)

Keith E. Latham Enders K. Ng Debra J. Wolgemuth Silvia Garagna Paul M. Wassarman

10.1159/000079515

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Switching of RNA splicing regulators in immature neuroblasts: a key step in adult neurogenesis

Corentin Bernou Marc‐André Mouthon Mathieu Daynac Benjamin Demaille Vilma Barroca

The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB or D cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into 2 subtypes, D1 and D2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.

Neuroblast

10.7554/elife.87083.1

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TGFβ Lengthens the G1 Phase of Stem Cells in Aged Mouse Brain

Stem Cells (2014)

Mathieu Daynac José Ramón Pineda Alexandra Chicheportiche Laurent Gauthier Lise Morizur

Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells.

10.1002/stem.1815

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Citations (37)

Switching of RNA splicing regulators in immature neuroblasts: a key step in adult neurogenesis

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Corentin Bernou Marc‐André Mouthon Mathieu Daynac Thierry Kortulewski Benjamin Demaille

Summary The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into 2 subtypes, iNB1 and iNB2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.

Neuroblast

10.1101/2023.03.12.532290

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Author Index Vol. 105, No. 2–4, 2004

Cytogenetic and Genome Research (2004)

Keith E. Latham Enders K. Ng Debra J. Wolgemuth Silvia Garagna Paul M. Wassarman

10.1159/000079514

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Author Response: Switching of RNA splicing regulators in immature neuroblasts: a key step in adult neurogenesis

Corentin Bernou Marc‐André Mouthon Mathieu Daynac Thierry Kortulewski Benjamin Demaille

The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into 2 subtypes, iNB1 and iNB2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.

Neuroblast

10.7554/elife.87083.2.sa3

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Switching of RNA splicing regulators in immature neuroblasts: a key step in adult neurogenesis

Corentin Bernou Marc‐André Mouthon Mathieu Daynac Thierry Kortulewski Benjamin Demaille

The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into 2 subtypes, iNB1 and iNB2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.

Neuroblast

10.7554/elife.87083.2

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Characterization ofSpo11-dependent and independent phospho-H2AX foci during meiotic prophase I in the male mouse

Journal of Cell Science (2007)

Alexandra Chicheportiche Jacqueline Bernardino-Sgherri Bernard de Massy Bernard Dutrillaux

Meiotic DNA double strand breaks (DSBs) are indicated at leptotene by the phosphorylated form of histone H2AX (γ-H2AX). In contrast to previous studies, we identified on both zygotene and pachytene chromosomes two distinct types of γ-H2AX foci: multiple small (S) foci located along autosomal synaptonemal complexes (SCs) and larger signals on chromatin loops (L-foci). The S-foci number gradually declined throughout pachytene, in parallel with the repair of DSBs monitored by repair proteins suggesting that S-foci mark DSB repair events. We validated this interpretation by showing the absence of S-foci in Spo11–/– spermatocytes. By contrast, the L-foci number was very low through pachytene. Based on the analysis of γ-H2AX labeling after irradiation of spermatocytes, the formation of DSBs clearly induced L-foci formation. Upon DSB repair, these foci appear to be processed and lead to the above mentioned S-foci. The presence of L-foci in wild-type pachytene and diplotene could therefore reflect delayed or unregulated DSB repair events. Interestingly, their distribution was different in Spo11+/– spermatocytes compared with Spo11+/+ spermatocytes, where DSB repair might be differently regulated as a response to homeostatic control of crossing-over. The presence of these L-foci in Spo11–/– spermatocytes raises the interesting possibility of yet uncharacterized alterations in DNA or chromosome structure in Spo11–/– cells.

Synaptonemal complex

Spermatocyte

10.1242/jcs.004945

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Citations (77)

Switching of RNA splicing regulators in immature neuroblasts during adult neurogenesis

eLife (2024)

Corentin Bernou Marc‐André Mouthon Mathieu Daynac Thierry Kortulewski Benjamin Demaille

The lateral wall of the mouse subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single-cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into two subtypes, iNB1 and iNB2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.

Neuroblast

10.7554/elife.87083.3

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Flow cytometric characterization of viable meiotic and postmeiotic cells by Hoechst 33342 in mouse spermatogenesis

Cytometry Part A (2005)

Henri Bastos Bruno Lassalle Alexandra Chicheportiche Lydia Riou J Testart

Abstract Background Spermatogenesis in adult is a complex stepwise process leading to terminally differentiated spermatozoa. The cellular heterogeneity of testis renders complex the studies on molecular aspects of this differentiation process. Analysis of the regulation of adult spermatogenesis would undoubtedly benefit from the development of techniques to characterize each germinal differentiation step. Methods Hoechst 33342 staining of mouse testicular cells allows characterization of an enriched population in germinal stem cell and spermatogonia, called side population. In this study, we examined the definition of the various germinal populations stained by Hoechst 33342, notably meiotic and postmeiotic cells. Results Preleptotene spermatocytes, spermatocyte I, spermatocyte II, and round and elongated spermatids were discriminated by Hoechst 33342 staining. In addition, we associated differentiation of spermatocyte I through leptotene to diplotene with changes in Hoechst 33342 red fluorescence pattern. Conclusions Hoechst 33342 staining of viable germinal cells constitutes a valuable tool to study normal and impaired mouse adult spermatogenesis or to isolate viable cells from various differentiation stages for studies of molecular mechanisms regulating spermatogenesis. © 2005 Wiley‐Liss, Inc.

Spermatocyte

10.1002/cyto.a.20129

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Citations (191)