ATP citrate lyase controls hematopoietic stem cell fate and supports bone marrow regeneration

ABSTRACT: In order to support bone marrow regeneration after myeloablation, hematopoietic stem cells (HSCs) actively divide to provide both stem and progenitor cells. However, the mechanisms regulating HSC function and cell fate choice during hematopoietic recovery remain unclear. We herein provide novel insights into HSC regulation during regeneration by focussing on mitochondrial metabolism and ATP citrate lyase (ACLY). After 5-fluorouracil-induced myeloablation, HSCs highly expressing endothelial protein C receptor (EPCRhigh) were enriched within the stem cell fraction at then expense of more proliferative EPCRLow HSCs. These EPCRHigh HSCs were initially more primitive than EPCRLow HSCs and enabled stem cell expansion by enhancing histone acetylation, due to increased activity of ACLY in the earl

SUBMITTER: Dr. Terumasa Umemoto 

PROVIDER: S-SCDT-EMBOJ-2021-109463 | biostudies-other |

REPOSITORIES: biostudies-other