Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis

Abstract Spermatogenesis is a complex process of cellular division and differentiation that begins with spermatogonia stem cells and leads to functional spermatozoa production. However, many of the molecular mechanisms underlying this process remain unclear. Single-cell RNA sequencing (scRNA-seq) is...

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Autores principales:	Najmeh Salehi, Mohammad Hossein Karimi-Jafari, Mehdi Totonchi, Amir Amiri-Yekta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4021ab1d2b5d46fe9c1e74172188b678
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spelling	oai:doaj.org-article:4021ab1d2b5d46fe9c1e74172188b6782021-12-02T17:37:35ZIntegration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis10.1038/s41598-021-98267-32045-2322https://doaj.org/article/4021ab1d2b5d46fe9c1e74172188b6782021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98267-3https://doaj.org/toc/2045-2322Abstract Spermatogenesis is a complex process of cellular division and differentiation that begins with spermatogonia stem cells and leads to functional spermatozoa production. However, many of the molecular mechanisms underlying this process remain unclear. Single-cell RNA sequencing (scRNA-seq) is used to sequence the entire transcriptome at the single-cell level to assess cell-to-cell variability. In this study, more than 33,000 testicular cells from different scRNA-seq datasets with normal spermatogenesis were integrated to identify single-cell heterogeneity on a more comprehensive scale. Clustering, cell type assignments, differential expressed genes and pseudotime analysis characterized 5 spermatogonia, 4 spermatocyte, and 4 spermatid cell types during the spermatogenesis process. The UTF1 and ID4 genes were introduced as the most specific markers that can differentiate two undifferentiated spermatogonia stem cell sub-cellules. The C7orf61 and TNP can differentiate two round spermatid sub-cellules. The topological analysis of the weighted gene co-expression network along with the integrated scRNA-seq data revealed some bridge genes between spermatogenesis’s main stages such as DNAJC5B, C1orf194, HSP90AB1, BST2, EEF1A1, CRISP2, PTMS, NFKBIA, CDKN3, and HLA-DRA. The importance of these key genes is confirmed by their role in male infertility in previous studies. It can be stated that, this integrated scRNA-seq of spermatogenic cells offers novel insights into cell-to-cell heterogeneity and suggests a list of key players with a pivotal role in male infertility from the fertile spermatogenesis datasets. These key functional genes can be introduced as candidates for filtering and prioritizing genotype-to-phenotype association in male infertility.Najmeh SalehiMohammad Hossein Karimi-JafariMehdi TotonchiAmir Amiri-YektaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Najmeh Salehi Mohammad Hossein Karimi-Jafari Mehdi Totonchi Amir Amiri-Yekta Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis
description	Abstract Spermatogenesis is a complex process of cellular division and differentiation that begins with spermatogonia stem cells and leads to functional spermatozoa production. However, many of the molecular mechanisms underlying this process remain unclear. Single-cell RNA sequencing (scRNA-seq) is used to sequence the entire transcriptome at the single-cell level to assess cell-to-cell variability. In this study, more than 33,000 testicular cells from different scRNA-seq datasets with normal spermatogenesis were integrated to identify single-cell heterogeneity on a more comprehensive scale. Clustering, cell type assignments, differential expressed genes and pseudotime analysis characterized 5 spermatogonia, 4 spermatocyte, and 4 spermatid cell types during the spermatogenesis process. The UTF1 and ID4 genes were introduced as the most specific markers that can differentiate two undifferentiated spermatogonia stem cell sub-cellules. The C7orf61 and TNP can differentiate two round spermatid sub-cellules. The topological analysis of the weighted gene co-expression network along with the integrated scRNA-seq data revealed some bridge genes between spermatogenesis’s main stages such as DNAJC5B, C1orf194, HSP90AB1, BST2, EEF1A1, CRISP2, PTMS, NFKBIA, CDKN3, and HLA-DRA. The importance of these key genes is confirmed by their role in male infertility in previous studies. It can be stated that, this integrated scRNA-seq of spermatogenic cells offers novel insights into cell-to-cell heterogeneity and suggests a list of key players with a pivotal role in male infertility from the fertile spermatogenesis datasets. These key functional genes can be introduced as candidates for filtering and prioritizing genotype-to-phenotype association in male infertility.
format	article
author	Najmeh Salehi Mohammad Hossein Karimi-Jafari Mehdi Totonchi Amir Amiri-Yekta
author_facet	Najmeh Salehi Mohammad Hossein Karimi-Jafari Mehdi Totonchi Amir Amiri-Yekta
author_sort	Najmeh Salehi
title	Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis
title_short	Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis
title_full	Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis
title_fullStr	Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis
title_full_unstemmed	Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis
title_sort	integration and gene co-expression network analysis of scrna-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4021ab1d2b5d46fe9c1e74172188b678
work_keys_str_mv	AT najmehsalehi integrationandgenecoexpressionnetworkanalysisofscrnaseqtranscriptomesrevealheterogeneityandkeyfunctionalgenesinhumanspermatogenesis AT mohammadhosseinkarimijafari integrationandgenecoexpressionnetworkanalysisofscrnaseqtranscriptomesrevealheterogeneityandkeyfunctionalgenesinhumanspermatogenesis AT mehditotonchi integrationandgenecoexpressionnetworkanalysisofscrnaseqtranscriptomesrevealheterogeneityandkeyfunctionalgenesinhumanspermatogenesis AT amiramiriyekta integrationandgenecoexpressionnetworkanalysisofscrnaseqtranscriptomesrevealheterogeneityandkeyfunctionalgenesinhumanspermatogenesis
_version_	1718379878039945216

Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis

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