Dissecting mammalian spermatogenesis using spatial transcriptomics.
Algorithms
Animals
Cellular Microenvironment
Databases, Genetic
Diabetes Mellitus
/ genetics
Disease Models, Animal
Gene Expression Profiling
Gene Expression Regulation, Developmental
Humans
Infertility, Male
/ genetics
Male
Mice
Mice, Inbred C57BL
Microscopy, Confocal
RNA-Seq
Single-Cell Analysis
Species Specificity
Spermatogenesis
/ genetics
Spermatogonia
/ metabolism
Testis
/ metabolism
Time Factors
Transcriptome
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
02 11 2021
02 11 2021
Historique:
received:
22
10
2020
revised:
20
07
2021
accepted:
11
10
2021
entrez:
3
11
2021
pubmed:
4
11
2021
medline:
16
2
2022
Statut:
ppublish
Résumé
Single-cell RNA sequencing has revealed extensive molecular diversity in gene programs governing mammalian spermatogenesis but fails to delineate their dynamics in the native context of seminiferous tubules, the spatially confined functional units of spermatogenesis. Here, we use Slide-seq, a spatial transcriptomics technology, to generate an atlas that captures the spatial gene expression patterns at near-single-cell resolution in the mouse and human testis. Using Slide-seq data, we devise a computational framework that accurately localizes testicular cell types in individual seminiferous tubules. Unbiased analysis systematically identifies spatially patterned genes and gene programs. Combining Slide-seq with targeted in situ RNA sequencing, we demonstrate significant differences in the cellular compositions of spermatogonial microenvironment between mouse and human testes. Finally, a comparison of the spatial atlas generated from the wild-type and diabetic mouse testis reveals a disruption in the spatial cellular organization of seminiferous tubules as a potential mechanism of diabetes-induced male infertility.
Identifiants
pubmed: 34731600
pii: S2211-1247(21)01388-7
doi: 10.1016/j.celrep.2021.109915
pmc: PMC8606188
mid: NIHMS1753635
pii:
doi:
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109915Subventions
Organisme : NIH HHS
ID : DP5 OD024583
Pays : United States
Organisme : NIBIB NIH HHS
ID : T32 EB001680
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010647
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG069725
Pays : United States
Organisme : NIA NIH HHS
ID : DP2 AG058488
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD056034
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests F.C. and E.Z.M. are listed as inventors on a pending patent application related to the development of Slide-seq. F.C. and E.Z.M. are paid consultants of Atlas Bio. The remaining authors declare no competing interests.
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