The fleet feet of haematopoietic stem cells: rapid motility, interaction and proteopodia.
Haematopoietic stem cells (HSCs) have been extensively characterized regarding in vivo engraftment, surface epitopes and genetic regulation. However, little is known about the homing of these rare cells, and their intrinsic motility and membrane deformation capacity. We used high-speed optical-sectioning microscopy and inverted fluorescent videomicroscopy to study highly purified murine lineage-negative, rhodamine-low, Hoechst-low HSCs over time under various in vitro conditions. We discovered extremely rapid motility, directed migration to stromal cells and marked membrane modulation. High resolution images with three-dimensional reconstruction showed the general presence of microspikes. Further, pseudopodia (proteopodia) were observed that were induced by stromal-derived factor-1 and steel factor. Proteopodia were directed towards and were quenched by stromal cells, at times bridged HSCs, and could rapidly retract or detach from cells. Proteopodia were also observed in vivo with homed HSCs in frozen sections of murine spleen, lung and heart. This is the first demonstration that HSCs are both fast and highly malleable in phenotype.
Frimberger
A E
AE
University of Massachusetts Cancer Center - NRI Building, University of Massachusetts, 55 Lake Avenue North, Worcester, MA 01655, USA. Angela.Frimberger@umassmed.edu
McAuliffe
C I
CI
Werme
K A
KA
Tuft
R A
RA
Fogarty
K E
KE
Benoit
B O
BO
Dooner
M S
MS
Quesenberry
P J
PJ
D000818:Animals; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D002469:Cell Separation; D022081:Cell Surface Extensions / Q000187:drug effects / Q000648:ultrastructure*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D018920:Coculture Techniques; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D019089:Stem Cell Factor / Q000494:pharmacology
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019089:Stem Cell Factor