Bcl11a controls Flt3 expression in early hematopoietic progenitors and is required for pDC development in vivo

Bcl11a is a transcription factor known to regulate lymphoid and erythroid development. Recent bioinformatic analysis of global gene expression patterns has suggested a role for Bcl11a in the development of dendritic cell (DC) lineages. We tested this hypothesis by analyzing the development of DC and other lineages in Bcl11a(-/-) mice. We show that Bcl11a is required for expression of IL-7 receptor (IL-7R) and Flt3 in early hematopoietic progenitor cells. The loss of IL-7R(+) common lymphoid progenitors accounts for previously described lymphoid defects in Bcl11a(-/-) mice. In addition, we found severely decreased numbers of plasmacytoid dendritic cells (pDCs) in Bcl11a(-/-) fetal livers and in the bone marrow of Bcl11a(-/-) fetal liver chimeras. Moreover, Bcl11a(-/-) cells show severely impaired in vitro development of Flt3L-derived pDCs and classical DCs (cDCs). In contrast, we found normal in vitro development of DCs from Bcl11a(-/-) fetal liver cells treated with GM-CSF. These results suggest that the persistent cDC development observed in Bcl11a(-/-) fetal liver chimeras reflects derivation from a Bcl11a- and Flt3-independent pathway in vivo.

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Wu X, Satpathy AT, Kc W, Liu P, Murphy TL, Murphy KM