Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages.
Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages.
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DOI：
10.1084/jem.20120030
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发表时间：
2012-06-04
期刊：
影响因子：
--
通讯作者：
Murphy KM
中科院分区：
文献类型：
--
作者：
Satpathy AT;KC W;Albring JC;Edelson BT;Kretzer NM;Bhattacharya D;Murphy TL;Murphy KM
锌指转录因子Zbtb 46特异性标记cDC及其定向前体，并且当在BM祖细胞中过表达时，以粒细胞为代价促进cDC发育。树突状细胞（DC）与单核吞噬细胞系统的其他细胞的区分是复杂的细胞表面标志物，如CD 11 c的共同表达。在这项研究中，我们确定Zbtb 46（BTBD 4）作为一种转录因子选择性表达的经典DC（cDC）和他们的定向祖细胞，但不浆细胞样DC（pDC），单核细胞，巨噬细胞，或其他淋巴或骨髓谱系。使用同源重组，我们用GFP替换了Zbtb 46的第一个编码外显子，以使基因座稳定，同时允许检测Zbtb 46的表达。Zbtb 46 gfp/+小鼠中的GFP表达重现了天然基因座的cDC特异性表达，仅限于cDC前体（pre-cDC）和淋巴器官和组织驻留的cDC。GFP+ pre-cDC具有受限的发育潜力，产生cDC而不是pDC、单核细胞或巨噬细胞。在免疫系统外，Zbtb 46在定向红系祖细胞和内皮细胞群体中表达。Zbtb 46在骨髓祖细胞中的过表达抑制粒细胞潜能并促进cDC发育，并且尽管在Zbtb 46 gfp/gfp（Zbtb 46缺陷）小鼠中发育cDC，但它们维持粒细胞集落刺激因子和白血病抑制因子受体的表达，这些受体在cDC中通常是下调的。因此，Zbtb 46可以通过限制对非DC生长因子的响应性来帮助加强cDC身份，并且可以用作鉴定稀有cDC祖细胞和区分cDC与其他单核吞噬细胞谱系的有用标记物。
The zinc finger transcription factor Zbtb46 specifically marks cDCs and their committed precursors and, when overexpressed in BM progenitors, promotes cDC development at the expense of granulocytes. Distinguishing dendritic cells (DCs) from other cells of the mononuclear phagocyte system is complicated by the shared expression of cell surface markers such as CD11c. In this study, we identified Zbtb46 (BTBD4) as a transcription factor selectively expressed by classical DCs (cDCs) and their committed progenitors but not by plasmacytoid DCs (pDCs), monocytes, macrophages, or other lymphoid or myeloid lineages. Using homologous recombination, we replaced the first coding exon of Zbtb46 with GFP to inactivate the locus while allowing detection of Zbtb46 expression. GFP expression in Zbtb46gfp/+ mice recapitulated the cDC-specific expression of the native locus, being restricted to cDC precursors (pre-cDCs) and lymphoid organ– and tissue-resident cDCs. GFP+ pre-cDCs had restricted developmental potential, generating cDCs but not pDCs, monocytes, or macrophages. Outside the immune system, Zbtb46 was expressed in committed erythroid progenitors and endothelial cell populations. Zbtb46 overexpression in bone marrow progenitor cells inhibited granulocyte potential and promoted cDC development, and although cDCs developed in Zbtb46gfp/gfp (Zbtb46 deficient) mice, they maintained expression of granulocyte colony-stimulating factor and leukemia inhibitory factor receptors, which are normally down-regulated in cDCs. Thus, Zbtb46 may help enforce cDC identity by restricting responsiveness to non-DC growth factors and may serve as a useful marker to identify rare cDC progenitors and distinguish between cDCs and other mononuclear phagocyte lineages.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
DOI：
10.1186/1745-7580-4-5
发表时间：
2008-04-29
期刊：
Immunome research
影响因子：
--
作者：
Lattin JE;Schroder K;Su AI;Walker JR;Zhang J;Wiltshire T;Saijo K;Glass CK;Hume DA;Kellie S;Sweet MJ
通讯作者：
Sweet MJ
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ