Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing

Gao, Shuai; Yan, Liying; Wang, Rui; Li, Jingyun; Yong, Jun; Zhou, Xin; Yuan, Wei; Wu, Xinglong; Wang, Xiaoye; Fan, Xiaoying; Yan, Jie; Zhi, Xu; Gao, Yun; Guo, Hongshan; Xiao, Jin; Wang, Wendong; Mao, Yunuo; Wang, Fengchao; Wen, Lu; Fu, Wei; Ge, Hao; Qiao, Jie; Tang, Fuchou

doi:10.1038/s41556-018-0105-4

Cited by 141 publications

(161 citation statements)

References 69 publications

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“…Of interest, LEFTY1 is a developmental gene, the role of which in adult tissue remains to be investigated. Recently, LEFTY1 has been identified as a marker of colonic stem cells both in fetal and adult large intestine . This is consistent with the LEFTY1 staining we observed in the normal colon.…”

Section: Discussionsupporting

confidence: 91%

Proteome analysis of formalin‐fixed paraffin‐embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas

Sohier

Sanson

Audebourg

et al. 2019

The Journal of Pathology

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Traditional serrated adenoma (TSA) remains the least understood of all the colorectal adenomas, although these lesions have been associated with a significant cancer risk, twice that of the conventional adenoma (CAD) and of the sessile serrated adenoma (SSA/P). This study was performed to investigate the proteomic profiles of the different colorectal adenomas to better understand the pathogenesis of TSA. We performed a global quantitative proteome analysis using the label‐free quantification (LFQ) method on 44 colorectal adenoma (12 TSAs, 15 CADs, and 17 SSA/Ps) and 17 normal colonic mucosa samples, archived as formalin‐fixed paraffin‐embedded blocks. Unsupervised consensus hierarchical clustering applied to the whole proteomic profile of the 44 colorectal adenomas identified four subtypes: C1 and C2 were well‐individualized clusters composed of all the CADs (15/15) and most of the SSA/Ps (13/17), respectively. This is consistent with the fact that CADs and SSA/Ps are homogeneous and distinct colorectal adenoma entities. In contrast, TSAs were subdivided into C3 and C4 clusters, consistent with the more heterogeneous entity of TSA at the morphologic and molecular levels. Comparison of the proteome expression profile between the adenoma subtypes and normal colonic mucosa further confirmed the heterogeneous nature of TSAs, which overlapped either on CADs or SSA/Ps, whereas CADs and SSAs formed homogeneous and distinct entities. Furthermore, we identified LEFTY1 a new potential marker for TSAs that may be relevant for the pathogenesis of TSA. LEFTY1 is an inhibitor of the Nodal/TGFβ pathway, which we found to be one of the most overexpressed proteins specifically in TSAs. This finding was confirmed by immunohistochemistry. Our study confirms that CADs and SSA/Ps form homogeneous and distinct colorectal adenoma entities, whereas TSAs are a heterogeneous entity and may arise from either SSA/Ps or from normal mucosa evolving through a process related to the CAD pathway. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussionsupporting

confidence: 91%

Proteome analysis of formalin‐fixed paraffin‐embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas

Sohier

Sanson

Audebourg

et al. 2019

The Journal of Pathology

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“…Thus, to capture the full spectrum of intestinal cell identities, we opted to use whole tissue single-nucleus extraction, over epithelial isolation and digestion, to process the engrafted colon for RNA-sequencing. Indeed, single- [25][26][27][28] , Reg4 in deep crypt secretory cells 29 , Myt1l, Asic2, and Syt1 in enteric neurons [30][31][32][33] , Vil1, Plac8, and Krt20 in enterocytes [34][35][36] , Nkx2-2, Chga, and Tph1 in enteroendocrine cells 37,38 , and Fcgbp, Muc2, and Clca1 in goblet cells 39,40 (Figs. 2G and S5C-E).…”

Section: Celltag Multiplexing Enables Long-term Tracking Of Cell Potementioning

confidence: 99%

CellTag Indexing: genetic barcode-based sample multiplexing for single-cell genomics

Guo

Kong

Kamimoto

et al. 2018

Preprint

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Single-cell technologies have seen rapid advancements in recent years, presenting new analytical challenges and opportunities. These high-throughput assays increasingly require special consideration in experimental design, sample multiplexing, batch effect removal, and data interpretation. Here, we describe a lentiviral barcode-based multiplexing approach, 'CellTag Indexing', where we transduce and label samples that can then be pooled together for downstream experimentation and analysis. By introducing predefined genetic barcodes that are transcribed and readily detected, we can reliably read out sample identity and transcriptional state via single-cell profiling. We validate and demonstrate the utility of CellTag Indexing by sequencing transcriptomes at single-cell resolution using a variety of cell types including mouse pre-B cells, primary mouse embryonic fibroblasts, and human HEK293T cells. A unique feature of CellTag Indexing is that the barcodes are heritable. This enables cell populations to be tagged, pooled and tracked over time within the same experimental replicate, then processed together to minimize unwanted biological and technical variation. We demonstrate this feature of CellTagging in long-term tracking of cell engraftment and differentiation, in vivo, in a mouse model of competitive transplant into the large intestine. Together, this presents CellTag Indexing as a broadly applicable genetic multiplexing tool that is complementary with existing single-cell technologies.

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“…[23][24][25][26] Prenatally digestive enzymes are expressed in the colon, whose proximal part is a derivative of the midgut. 27 After 8 weeks of pregnancy a simple tube develops into an early gut; enzymes like SI, alkaline phosphatase, Dipeptidylpeptidase 4 (DPPIV), and ApN can be measured and a villous structure builds up. 28 Until the 30th week of pregnancy the colon shows a low but stable expression of SI and LPH.…”

Section: Introductionmentioning

confidence: 99%

Digestive enzyme expression in the large intestine of children with short bowel syndrome in a late stage of adaptation

et al. 2020

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Background and aims: Intestinal adaptation in short bowel syndrome (SBS) includes morphologic processes and functional mechanisms. This study investigated whether digestive enzyme expression in the duodenum and colon is upregulated in SBS patients. Method: Sucrase‐isomaltase (SI), lactase‐phlorizin hydrolase (LPH), and neutral Aminopeptidase N (ApN) were analyzed in duodenal and colonic biopsies from nine SBS patients in a late stage of adaptation as well as healthy and disease controls by immunoelectron microscopy (IEM), Western blots, and enzyme activities. Furthermore, proliferation rates and intestinal microbiota were analyzed in the mucosal specimen. Results: We found significantly increased amounts of SI, LPH, and ApN in colonocytes in most SBS patients with large variation and strongest effect for SI and ApN. Digestive enzyme expression was only partially elevated in duodenal enterocytes due to a low proliferation level measured by Ki‐67 staining. Microbiome analysis revealed high amounts of Lactobacillus resp. low amounts of Proteobacteria in SBS patients with preservation of colon and ileocecal valve. Colonic expression was associated with a better clinical course in single cases. Conclusion: In SBS patients disaccharidases and peptidases can be upregulated in the colon. Stimulation of this colonic intestinalization process by drugs, nutrients, and pre‐ or probiotics might offer better therapeutic approaches.

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Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing

Cited by 141 publications

References 69 publications

Proteome analysis of formalin‐fixed paraffin‐embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas

Proteome analysis of formalin‐fixed paraffin‐embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas

CellTag Indexing: genetic barcode-based sample multiplexing for single-cell genomics

Digestive enzyme expression in the large intestine of children with short bowel syndrome in a late stage of adaptation

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