N-cadherin in osteolineage cells is not required for maintenance of hematopoietic stem cells.
There is evidence suggesting that N-cadherin expression on osteoblast lineage cells regulates hematopoietic stem cell (HSC) function and quiescence. To test this hypothesis, we conditionally deleted N-cadherin (Cdh2) in osteoblasts using Cdh2(flox/flox) Osx-Cre mice. N-cadherin expression was efficiently ablated in osteoblast lineage cells as assessed by mRNA expression and immunostaining of bone sections. Basal hematopoiesis is normal in these mice. In particular, HSC number, cell cycle status, long-term repopulating activity, and self-renewal capacity were normal. Moreover, engraftment of wild-type cells into N-cadherin-deleted recipients was normal. Finally, these mice responded normally to G-CSF, a stimulus that mobilizes HSCs by inducing alterations to the stromal micro-environment. In conclusion, N-cadherin expression in osteoblast lineage cells is dispensable for HSC maintenance in mice.
Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Adam M
AM
Greenbaum
Leila D
LD
Revollo
Jill R
JR
Woloszynek
Roberto
R
Civitelli
Daniel C
DC
Link
D000818:Animals; D001483:Base Sequence; D001851:Bone Diseases, Metabolic / Q000209:etiology; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D015820:Cadherins; C489083:Cdh2 protein, mouse; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005472:Fluorouracil