Your browser doesn't support javascript.
loading
Transcripts of repetitive DNA elements signal to block phagocytosis of hematopoietic stem cells.
Pessoa Rodrigues, Cecilia; Collins, Joseph M; Yang, Song; Martinez, Catherine; Kim, Ji Wook; Lama, Chhiring; Nam, Anna S; Alt, Clemens; Lin, Charles; Zon, Leonard I.
Afiliación
  • Pessoa Rodrigues C; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.
  • Collins JM; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA.
  • Yang S; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.
  • Martinez C; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA.
  • Kim JW; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.
  • Lama C; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA.
  • Nam AS; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.
  • Alt C; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA.
  • Lin C; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
  • Zon LI; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Science ; 385(6714): eadn1629, 2024 Sep 13.
Article en En | MEDLINE | ID: mdl-39264994
ABSTRACT
Macrophages maintain hematopoietic stem cell (HSC) quality by assessing cell surface Calreticulin (Calr), an "eat-me" signal induced by reactive oxygen species (ROS). Using zebrafish genetics, we identified Beta-2-microglobulin (B2m) as a crucial "don't eat-me" signal on blood stem cells. A chemical screen revealed inducers of surface Calr that promoted HSC proliferation without triggering ROS or macrophage clearance. Whole-genome CRISPR-Cas9 screening showed that Toll-like receptor 3 (Tlr3) signaling regulated b2m expression. Targeting b2m or tlr3 reduced the HSC clonality. Elevated B2m levels correlated with high expression of repetitive element (RE) transcripts. Overall, our data suggest that RE-associated double-stranded RNA could interact with TLR3 to stimulate surface expression of B2m on hematopoietic stem and progenitor cells. These findings suggest that the balance of Calr and B2m regulates macrophage-HSC interactions and defines hematopoietic clonality.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fagocitosis / Células Madre Hematopoyéticas / Microglobulina beta-2 / Calreticulina / Receptor Toll-Like 3 / Macrófagos Límite: Animals Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fagocitosis / Células Madre Hematopoyéticas / Microglobulina beta-2 / Calreticulina / Receptor Toll-Like 3 / Macrófagos Límite: Animals Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos