Failure of transdifferentiation of adult hematopoietic stem cells into neurons.
Previous studies of bone marrow-derived stem cell transdifferentiation into neurons have not involved purified cell populations and determined their exact phenotype prior to differentiation. The present study investigates whether highly purified mouse adult hematopoietic stem cells (HSCs), characterized by lineage marker depletion and expression of the cell surface markers Sca1 and c-Kit (Lin(-) Sca1(+) c-Kit(+) [LSK]), can be stimulated to adopt a neuronal fate. When the HSC(LSK) cells were cultured in vitro in neuronal differentiation medium supplemented with retinoic acid, 50% of the cells expressed the neural progenitor marker nestin and no cells had become postmitotic. Electrophysiological recordings on neuron-like cells showed that these cells were incapable of generating action potentials. When the HSC(LSK) cells either were grown in vitro together with neural precursor cells or were transplanted into the striatum or cerebellum of wild-type mouse, they either differentiated into Iba1-immunopositive macrophage/microglia or died. In conclusion, we demonstrate that adult HSC(LSK) cells do not have the capacity to leave the hematopoietic lineage and differentiate into neurons.
Roybon
Laurent
L
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund, Sweden. Laurent.Roybon@med.lu.se
Ma
Zhi
Z
Asztely
Fredrik
F
Fosum
Anna
A
Jacobsen
Sten Eirik W
SE
Brundin
Patrik
P
Li
Jia-Yi
JY
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D004594:Electrophysiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology*; D014404:Tubulin / Q000378:metabolism
D015415:Biomarkers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D014404:Tubulin; C462941:beta3 tubulin, mouse; D049452:Green Fluorescent Proteins