A Population of M2 Macrophages Associated With Bone Formation.
A Population of M2 Macrophages Associated With Bone Formation.
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DOI：
10.3389/fimmu.2021.686769
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发表时间：
2021
影响因子：
7.3
通讯作者：
Davis AR
中科院分区：
文献类型：
--
作者：
Olmsted-Davis E;Mejia J;Salisbury E;Gugala Z;Davis AR
我们先前发现了与异位骨化(HO)相关的一过性棕色脂肪细胞样细胞。这些辅助细胞支持骨形成所必需的新血管合成。最近的研究表明，M2巨噬细胞以类似的方式促进组织再生。为了进一步确定这些棕色脂肪细胞样细胞的表型，我们分离了它们，并用单细胞RNAseq(ScRNAseq)对其进行了鉴定。对转录组的分析和巨噬细胞表面标志物的存在表明，这些细胞是M2巨噬细胞。为了验证这些发现，在HO期间将氯屈膦酸盐脂质体输送到组织中，结果显示这些巨噬细胞和骨形成都显著减少。这些细胞被分离出来，在培养中显示向M1或M2极化，类似于其他巨噬细胞。为了确认这些是M2巨噬细胞，小鼠接受了脂多糖(LPS)，它诱导了前炎症和M1巨噬细胞。结果显示，这一特定群体和骨形成显著减少，表明M2巨噬细胞在骨产生中发挥重要作用。为了确定这些巨噬细胞是否是HO特异性的，我们使用荧光激活细胞分选(FACS)从骨缺损模型中分离出这些细胞，并对它们进行scRNAseq。令人惊讶的是，两组之间的巨噬细胞群重叠(HO来源的和骨痂)，这表明它们可能是骨形成的基本辅助细胞，而不是HO的选择性。更值得注意的是，它们独特的新陈代谢和造脂特性表明，这些细胞和新形成的骨之间可能存在独特的串扰。
We previously identified transient brown adipocyte-like cells associated with heterotopic ossification (HO). These ancillary cells support new vessel synthesis essential to bone formation. Recent studies have shown that the M2 macrophage contributes to tissue regeneration in a similar way. To further define the phenotype of these brown adipocyte-like cells they were isolated and characterized by single-cell RNAseq (scRNAseq). Analysis of the transcriptome and the presence of surface markers specific for macrophages suggest that these cells are M2 macrophages. To validate these findings, clodronate liposomes were delivered to the tissues during HO, and the results showed both a significant reduction in these macrophages as well as bone formation. These cells were isolated and shown in culture to polarize towards either M1 or M2 similar to other macrophages. To confirm that these are M2 macrophages, mice received lipopolysacheride (LPS), which induces proinflammation and M1 macrophages. The results showed a significant decrease in this specific population and bone formation, suggesting an essential role for M2 macrophages in the production of bone. To determine if these macrophages are specific to HO, we isolated these cells using fluorescence-activated cell sorting (FACS) from a bone defect model and subjected them to scRNAseq. Surprisingly, the macrophage populations overlapped between the two groups (HO-derived versus callus) suggesting that they may be essential ancillary cells for bone formation in general and not selective to HO. Of further note, their unique metabolism and lipogenic properties suggest the potential for unique cross talk between these cells and the newly forming bone.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
7.7
作者：
Jiang Y;Berry DC;Graff JM
通讯作者：
Graff JM
影响因子：
4.2
作者：
Fouletier-Dilling, Christine M.;Gannon, Francis H.;Davis, Alan R.
通讯作者：
Davis, Alan R.
影响因子：
7.3
作者：
Diskin C;Pålsson-McDermott EM
通讯作者：
Pålsson-McDermott EM
影响因子：
6
作者：
Mejia J;Salisbury E;Sonnet C;Gugala Z;Olmsted-Davis EA;Davis AR
通讯作者：
Davis AR