A large pool of actively cycling progenitors orchestrates self-renewal and injury repair of an ectodermal appendage

The classical model of tissue renewal posits that small numbers of quiescent stem cells (SCs) give rise to proliferating transit-amplifying cells before terminal differentiation. However, many organs house pools of SCs with proliferative and differentiation potentials that diverge from this template. Resolving SC identity and organization is therefore central to understanding tissue renewal. Here, using a combination of single-cell RNA sequencing (scRNA-seq), mouse genetics and tissue injury approaches, we uncover cellular hierarchies and mechanisms that underlie the maintenance and repair of the continuously growing mouse incisor. Our results reveal that, during homeostasis, a group of actively cycling epithelial progenitors generates enamel-producing ameloblasts and adjacent layers of non-ameloblast cells. After injury, tissue repair was achieved through transient increases in progenitor-cell proliferation and through direct conversion of Notch1-expressing cells to ameloblasts. We elucidate epithelial SC identity, position and function, providing a mechanistic basis for the homeostasis and repair of a fast-turnover ectodermal appendage

COME SWING WITH ME ! / Frank Sinatra avec Orchestre dir. Billy May

Titre uniforme : [Day by day]Titre uniforme : [Five minutes more]Titre uniforme : [Lover]Titre uniforme : [On the sunny side side of the street]Titre uniforme : [Sentimental journey]Titre uniforme : [Lover = l'Amour est un rêve]Titre uniforme : [Sentimental journey]Titre uniforme : [On the sunny side of the street]Titre uniforme : [Sentimental journey]Comprend : DAY BY DAY / Stordahl ; Weston et Cahn - SENTIMENTAL JOURNEY / Brown ; Homer et Green - ALMOST LIKE BEING IN LOVE / Frederick Loewe et Alan Jay Lerner - FIVE MINUTES MORE / Sammy Cahn Jr et Jule Styne - AMERICAN BEAUTY ROSE / David ; Evans et Altman - YES INDEED ! / Sy Oliver - ON THE SUNNY SIDE OF THE STREET / Jimmy McHugh et Dorothy Fields - DON'T TAKE YOUR LOVE FROM ME / Henry Nemo - THAT OLD BLACK MAGIC / Harold Arlen et Johnny Mercer - LOVER / Richard Rodgers et Lorenz Hart - PAPER DOLL / Johnny S. Black - I'VE HEARD THAT SONG BEFORE / Jule Styne et Sammy CahnBnF-Partenariats, Collection sonore - BelieveContient une table des matière

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele