Clump sequencing exposes the spatial expression programs of intestinal secretory cells.

Clump sequencing exposes the spatial expression programs of intestinal secretory cells.
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DOI:
10.1038/s41467-021-23245-2
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发表时间:
2021-05-24
影响因子:
16.6
通讯作者:
Itzkovitz S
Itzkovitz S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Manco R;Averbukh I;Porat Z;Bahar Halpern K;Amit I;Itzkovitz S

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单细胞RNA测序与地标基因的空间信息相结合,能够重建空间分辨的组织细胞图谱。然而,这种方法对于稀有细胞类型是具有挑战性的,因为它们的mRNA含量在用于地标基因检测的空间转录组学批量测量中被稀释。在小肠中,肠上皮细胞,最常见的细胞类型,表现出分区的表达程序沿着隐窝绒毛轴,但分区模式的罕见的细胞类型,如杯状细胞和簇状细胞仍然没有特征。在这里,我们提出了ClumpSeq,一种对附着细胞的小团块进行测序的方法。通过从肠上皮细胞标志基因推断每个团块的隐窝-绒毛位置,我们建立了小肠中所有上皮细胞类型的空间图谱。我们确定了绒毛尖杯状细胞和簇状细胞中免疫调节基因的表达升高以及肠内分泌细胞的异质迁移模式。ClumpSeq可用于重建其他组织和肿瘤中罕见细胞类型的空间图谱。将scRNA-seq与空间信息相结合以重建空间分辨的细胞图谱对于罕见的细胞类型是具有挑战性的。在这里,作者介绍了ClumpSeq,一种对小团组织附着细胞进行测序的方法,并将其应用于建立小肠中所有分泌细胞类型的空间图谱。
Single-cell RNA sequencing combined with spatial information on landmark genes enables reconstruction of spatially-resolved tissue cell atlases. However, such approaches are challenging for rare cell types, since their mRNA contents are diluted in the spatial transcriptomics bulk measurements used for landmark gene detection. In the small intestine, enterocytes, the most common cell type, exhibit zonated expression programs along the crypt-villus axis, but zonation patterns of rare cell types such as goblet and tuft cells remain uncharacterized. Here, we present ClumpSeq, an approach for sequencing small clumps of attached cells. By inferring the crypt-villus location of each clump from enterocyte landmark genes, we establish spatial atlases for all epithelial cell types in the small intestine. We identify elevated expression of immune-modulatory genes in villus tip goblet and tuft cells and heterogeneous migration patterns of enteroendocrine cells. ClumpSeq can be applied for reconstructing spatial atlases of rare cell types in other tissues and tumors. Combining scRNA-seq with spatial information to enable the reconstruction of spatially-resolved cell atlases is challenging for rare cell types. Here the authors present ClumpSeq, an approach for sequencing small clumps of tissue attached cells, and apply it to establish spatial atlases for all secretory cell types in the small intestine.
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