title: Mitochondrial respiration defects modulate differentiation but not proliferation of hematopoietic stem and progenitor cells.
abstract: Mitochondrial energy production is involved in various cellular processes. Here we show that ATP content is significantly increased in lineage-restricted progenitor cells compared with hematopoietic stem and progenitor cells (HSPCs) or more differentiated cells. Transplantation analysis using a mouse model of mitochondrial disease revealed that mitochondrial respiration defects resulted in a significant decrease in the total number and repopulating activity of bone marrow cells, although the number of HSPCs increased. The proliferative activity of HSPCs and lineage-restricted progenitor cells was not impaired by reduction of ATP content and there seems to be no associated increase in reactive oxygen species levels and apoptosis. Our findings indicate that mitochondrial respiration defects modulate HSPC commitment/differentiation into lineage-restricted progenitor cells.
authors.affiliation: Subteam for Manipulation of Cell Fate, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Inoue
authors.forename: Shinichi
authors.initials: S
authors.lastname: Noda
authors.forename: Koutarou
authors.initials: K
authors.lastname: Kashima
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakada
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D019069:Cell Respiration; D004272:DNA, Mitochondrial / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate