Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition.

Cell Cycle Cell Division Cell Self Renewal Hematopoietic Stem Cells / metabolism Mitochondria

Journal

Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472

Informations de publication

Date de publication:
05 03 2020
Historique:
received: 15 09 2019
revised: 29 10 2019
accepted: 23 01 2020
pubmed: 16 2 2020
medline: 28 4 2021
entrez: 16 2 2020
Statut: ppublish

Résumé

The metabolic requirements of hematopoietic stem cells (HSCs) change with their cell cycle activity. However, the underlying role of mitochondria remains ill-defined. Here we found that, after mitochondrial activation with replication, HSCs irreversibly remodel the mitochondrial network and that this network is not repaired after HSC re-entry into quiescence, contrary to hematopoietic progenitors. HSCs keep and accumulate dysfunctional mitochondria through asymmetric segregation during active division. Mechanistically, mitochondria aggregate and depolarize after stress because of loss of activity of the mitochondrial fission regulator Drp1 onto mitochondria. Genetic and pharmacological studies indicate that inactivation of Drp1 causes loss of HSC regenerative potential while maintaining HSC quiescence. Molecularly, HSCs carrying dysfunctional mitochondria can re-enter quiescence but fail to synchronize the transcriptional control of core cell cycle and metabolic components in subsequent division. Thus, loss of fidelity of mitochondrial morphology and segregation is one type of HSC divisional memory and drives HSC attrition.

Identifiants

DOI: 10.1016/j.stem.2020.01.016 PMID: 32059807 PMC: PMC7212526
pubmed: 32059807
pii: S1934-5909(20)30016-3
doi: 10.1016/j.stem.2020.01.016
pmc: PMC7212526
mid: NIHMS1568883
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

420-430.e6

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL122661
Pays : United States
Organisme : NIH HHS
ID : S10 OD023410
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR070549
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102890
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI135595
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM130695
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL090676
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Ashwini Hinge (A)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Jingyi He (J)

Pediatric Research Institute, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R China.

James Bartram (J)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Jose Javier (J)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Juying Xu (J)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Ellen Fjellman (E)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Hiromi Sesaki (H)

Department of Cell Biology, John Hopkins University School of Medicine, Baltimore, MD, USA.

Tingyu Li (T)

Child Nutrition Research Center in the Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Nutrition and Health, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, P.R China.

Jie Yu (J)

Department of Hematology and Oncology, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R China.

Mark Wunderlich (M)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

James Mulloy (J)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Matthew Kofron (M)

Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.

Nathan Salomonis (N)

Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.

H Leighton Grimes (HL)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Immunobiology and Center for Systems Immunology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.

Marie-Dominique Filippi (MD)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: marie-dominique.filippi@cchmc.org.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques cellulaires › Cycle cellulaire › Asymmetrically Segregated Mitochondria Provide...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Division cellulaire › Asymmetrically Segregated Mitochondria Provide...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Division cellulaire › Auto-renouvellement cellulaire › Asymmetrically Segregated Mitochondria Provide...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Asymmetrically Segregated Mitochondria Provide...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Asymmetrically Segregated Mitochondria Provide...