Contractile forces sustain and polarize hematopoiesis from stem and progenitor cells.
Cell Stem Cell
; 14(1): 81-93, 2014 Jan 02.
Article
in En
| MEDLINE
| ID: mdl-24268694
ABSTRACT
Self-renewal and differentiation of stem cells depend on asymmetric division and polarized motility processes that in other cell types are modulated by nonmuscle myosin-II (MII) forces and matrix mechanics. Here, mass spectrometry-calibrated intracellular flow cytometry of human hematopoiesis reveals MIIB to be a major isoform that is strongly polarized in hematopoietic stem cells and progenitors (HSC/Ps) and thereby downregulated in differentiated cells via asymmetric division. MIIA is constitutive and activated by dephosphorylation during cytokine-triggered differentiation of cells grown on stiff, endosteum-like matrix, but not soft, marrow-like matrix. In vivo, MIIB is required for generation of blood, while MIIA is required for sustained HSC/P engraftment. Reversible inhibition of both isoforms in culture with blebbistatin enriches for long-term hematopoietic multilineage reconstituting cells by 5-fold or more as assessed in vivo. Megakaryocytes also become more polyploid, producing 4-fold more platelets. MII is thus a multifunctional node in polarized division and niche sensing.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hematopoietic Stem Cells
/
Cell Differentiation
/
Cell Movement
/
Nonmuscle Myosin Type IIA
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Nonmuscle Myosin Type IIB
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Hematopoiesis
/
Muscle Contraction
Limits:
Humans
Language:
En
Journal:
Cell Stem Cell
Year:
2014
Document type:
Article
Affiliation country:
Estados Unidos