Clump sequencing exposes the spatial expression programs of intestinal secretory cells.
Animals
Biological Transport
/ genetics
Cell Differentiation
Computational Biology
/ methods
Enterocytes
/ metabolism
Enteroendocrine Cells
/ metabolism
Epithelial Cells
/ metabolism
Epithelium
Gene Expression
Intestinal Mucosa
/ metabolism
Intestine, Small
/ metabolism
Intestines
/ physiology
Mice
Mice, Inbred C57BL
RNA, Messenger
/ metabolism
Sequence Analysis, RNA
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 05 2021
24 05 2021
Historique:
received:
10
09
2020
accepted:
22
04
2021
entrez:
25
5
2021
pubmed:
26
5
2021
medline:
16
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34031373
doi: 10.1038/s41467-021-23245-2
pii: 10.1038/s41467-021-23245-2
pmc: PMC8144370
doi:
Substances chimiques
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3074Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
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