Microtubules control nuclear shape and gene expression during early stages of hematopoietic differentiation.
chromatin remodeling
differentiation
microtubule
nucleus deformation
stem cells
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
08
11
2019
revised:
17
09
2020
accepted:
24
09
2020
pubmed:
23
10
2020
medline:
13
4
2021
entrez:
22
10
2020
Statut:
ppublish
Résumé
Hematopoietic stem and progenitor cells (HSPC) can differentiate into all hematopoietic lineages to support hematopoiesis. Cells from the myeloid and lymphoid lineages fulfill distinct functions with specific shapes and intra-cellular architectures. The role of cytokines in the regulation of HSPC differentiation has been intensively studied but our understanding of the potential contribution of inner cell architecture is relatively poor. Here, we show that large invaginations are generated by microtubule constraints on the swelling nucleus of human HSPC during early commitment toward the myeloid lineage. These invaginations are associated with a local reduction of lamin B density, local loss of heterochromatin H3K9me3 and H3K27me3 marks, and changes in expression of specific hematopoietic genes. This establishes the role of microtubules in defining the unique lobulated nuclear shape observed in myeloid progenitor cells and suggests that this shape is important to establish the gene expression profile specific to this hematopoietic lineage. It opens new perspectives on the implications of microtubule-generated forces, in the early commitment to the myeloid lineage.
Identifiants
pubmed: 33089509
doi: 10.15252/embj.2019103957
pmc: PMC7705455
doi:
Substances chimiques
Cytokines
0
Histones
0
Banques de données
GEO
['GSE157349']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e103957Subventions
Organisme : Agence Nationale pour la Recherche (ANR)
ID : ANR-14-CE11-0012
Organisme : Agence Nationale pour la Recherche (ANR)
ID : ANR-10-IHUB-0002
Organisme : EC|H2020|H2020 Priority Excellent Science|H2020 European Research Council (ERC)
ID : ERC CoG 771599
Organisme : Fondation pour la recherche medicale
ID : FDT20170437071
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The Authors.
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