Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo.
The development of functionally specialized subtypes of dendritic cells (DCs) can be modeled through the culture of bone marrow with the ligand for the cytokine receptor Flt3. Such cultures produce DCs resembling spleen plasmacytoid DCs (pDCs), CD8(+) conventional DCs (cDCs) and CD8(-) cDCs. Here we isolated two sequential DC-committed precursor cells from such cultures: dividing 'pro-DCs', which gave rise to transitional 'pre-DCs' en route to differentiating into the three distinct DC subtypes (pDCs, CD8(+) cDCs and CD8(-) cDCs). We also isolated an in vivo equivalent of the DC-committed pro-DC precursor cell, which also gave rise to the three DC subtypes. Clonal analysis of the progeny of individual pro-DC precursors demonstrated that some pro-DC precursors gave rise to all three DC subtypes, some produced cDCs but not pDCs, and some were fully committed to a single DC subtype. Thus, commitment to particular DC subtypes begins mainly at this pro-DC stage.
Naik
Shalin H
SH
The Walter and Eliza Hall Institute, Parkville, Victoria 3050, Australia. s.naik@nki.nl
Sathe
Priyanka
P
Park
Hae-Young
HY
Metcalf
Donald
D
Proietto
Anna I
AI
Dakic
Aleksander
A
Carotta
Sebastian
S
O'Keeffe
Meredith
M
Bahlo
Melanie
M
Papenfuss
Anthony
A
Kwak
Jong-Young
JY
Wu
Li
L
Shortman
Ken
K
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D008565:Membrane Proteins; C084881:flt3 ligand protein