Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages.
Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages.
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DOI：
10.3389/fgene.2021.756028
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发表时间：
2021
影响因子：
3.7
通讯作者：
Bieker JJ
中科院分区：
文献类型：
--
作者：
Mukherjee K;Bieker JJ
在最终的红细胞生成过程中，红系祖细胞成熟为去核网织红细胞需要红系造血岛(EBI)生态位，其中包括一个附着在分化的红系祖细胞上的中央巨噬细胞。正常情况下，巨噬细胞为红系细胞的成熟提供了滋养环境。它关键的生理重要性需要帮助从贫血的侮辱中恢复，例如全身压力或获得性疾病。对表征岛龛中央巨噬细胞的极大兴趣导致了对富含于岛屿巨噬细胞的假定细胞表面标记的鉴定，从而能够分离和鉴定。最近的研究集中在成人稳态红细胞生成和胚胎红细胞生成过程中岛状巨噬细胞的批量和单细胞转录。它们揭示了岛状巨噬细胞是一种不同的细胞类型，但具有广泛的细胞异质性，可能表明不同的发育来源和生物学功能。这些研究还发现了驱动岛状巨噬细胞基因表达的转录程序。值得注意的是，主要的红系调节因子EKLF/KLF1似乎也在调节岛状巨噬细胞的基因表达方面发挥了重要作用，包括可能依赖于EKLF/KLF1的转录电路。我们目前对小鼠单细胞遗传模式的回顾和分析表明，新的表达特征将使EBI亚型的明显丰富和岛状巨噬细胞的异质性得到解决。具体地说，EPOR等标志物的发现，以及表达EKLF/KLF1的岛状巨噬细胞(如Sptb和Add2)、SPIC表达的岛状巨噬细胞(如Timd4)或表达Maf/Nr1h3的岛状巨噬细胞(如Vcam1)的特异性特征的发现，为进一步表征这些独特的巨噬细胞类型的关键发育功能提供了令人兴奋的可能性。
During definitive erythropoiesis, maturation of erythroid progenitors into enucleated reticulocytes requires the erythroblastic island (EBI) niche comprising a central macrophage attached to differentiating erythroid progenitors. Normally, the macrophage provides a nurturing environment for maturation of erythroid cells. Its critical physiologic importance entails aiding in recovery from anemic insults, such as systemic stress or acquired disease. Considerable interest in characterizing the central macrophage of the island niche led to the identification of putative cell surface markers enriched in island macrophages, enabling isolation and characterization. Recent studies focus on bulk and single cell transcriptomics of the island macrophage during adult steady-state erythropoiesis and embryonic erythropoiesis. They reveal that the island macrophage is a distinct cell type but with widespread cellular heterogeneity, likely suggesting distinct developmental origins and biological function. These studies have also uncovered transcriptional programs that drive gene expression in the island macrophage. Strikingly, the master erythroid regulator EKLF/Klf1 seems to also play a major role in specifying gene expression in island macrophages, including a putative EKLF/Klf1-dependent transcription circuit. Our present review and analysis of mouse single cell genetic patterns suggest novel expression characteristics that will enable a clear enrichment of EBI subtypes and resolution of island macrophage heterogeneity. Specifically, the discovery of markers such as Epor, and specific features for EKLF/Klf1-expressing island macrophages such as Sptb and Add2, or for SpiC-expressing island macrophage such as Timd4, or for Maf/Nr1h3-expressing island macrophage such as Vcam1, opens exciting possibilities for further characterization of these unique macrophage cell types in the context of their critical developmental function.
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影响因子：
64.5
作者：
Haldar M;Kohyama M;So AY;Kc W;Wu X;Briseño CG;Satpathy AT;Kretzer NM;Arase H;Rajasekaran NS;Wang L;Egawa T;Igarashi K;Baltimore D;Murphy TL;Murphy KM
通讯作者：
Murphy KM
影响因子：
10.1
作者：
Heideveld E;Hampton-O'Neil LA;Cross SJ;van Alphen FPJ;van den Biggelaar M;Toye AM;van den Akker E
通讯作者：
van den Akker E
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
20.3
作者：
Korolnek, Tamara;Hamza, Iqbal
通讯作者：
Hamza, Iqbal
影响因子：
20.3
作者：
Chen, Yuanting;Xiang, Jie;Paulson, Robert F.
通讯作者：
Paulson, Robert F.