<i>Tmsb10</i> triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway

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Abstract

Leydig cells in fetal testes play crucial roles in masculinizing fetuses through androgen production. Gene knockout studies have revealed that growth factors are implicated in fetal Leydig cell (FLC) differentiation, but little is known about the mechanisms regulating this process. We investigate this issue by characterizing FLC progenitor cells using single-cell RNA sequencing. The sequence datasets suggest that thymosin β10 ( Tmsb10) is transiently upregulated in the progenitors. While studying the function of Tmsb10, we reveal that platelet-derived growth factor (PDGF) regulates ciliogenesis through the RAS/ERK and PI3K/AKT pathways, and thereby promotes desert hedgehog (DHH)-dependent FLC differentiation. Tmsb10 expressed in the progenitor cells induces their differentiation into FLCs by suppressing the RAS/ERK pathway. Through characterizing the transiently expressed Tmsb10 in the FLC progenitors, this study unveils the molecular process of FLC differentiation and shows that it is cooperatively induced by DHH and PDGF.

Abstract

Investigation of fetal Leydig progenitors shows that thymosin β10 ( Tmsb10) suppresses the RAS/ERK pathway, inducing progenitor differentiation into fetal Leydig cells.

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Most cited references 71

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Fast gapped-read alignment with Bowtie 2.

Ben Langmead, Steven L Salzberg (2022)

As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.

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HTSeq—a Python framework to work with high-throughput sequencing data

Simon Anders, Paul Pyl, Wolfgang Huber (2014)

Motivation: A large choice of tools exists for many standard tasks in the analysis of high-throughput sequencing (HTS) data. However, once a project deviates from standard workflows, custom scripts are needed. Results: We present HTSeq, a Python library to facilitate the rapid development of such scripts. HTSeq offers parsers for many common data formats in HTS projects, as well as classes to represent data, such as genomic coordinates, sequences, sequencing reads, alignments, gene model information and variant calls, and provides data structures that allow for querying via genomic coordinates. We also present htseq-count, a tool developed with HTSeq that preprocesses RNA-Seq data for differential expression analysis by counting the overlap of reads with genes. Availability and implementation: HTSeq is released as an open-source software under the GNU General Public Licence and available from http://www-huber.embl.de/HTSeq or from the Python Package Index at https://pypi.python.org/pypi/HTSeq. Contact: sanders@fs.tum.de

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A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

Martin Jinek, Krzysztof Chylinski, Ines Fonfara … (2012)

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.

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Author and article information

Contributors

Ken-ichirou Morohashi: morohashi.ken-ichirou.874@m.kyushu-u.ac.jp

Journal

Journal ID (nlm-ta): Commun Biol

Journal ID (iso-abbrev): Commun Biol

Title: Communications Biology

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2399-3642

Publication date (Electronic): 15 September 2022

Publication date PMC-release: 15 September 2022

Publication date Collection: 2022

Volume: 5

Electronic Location Identifier: 974

Affiliations

[1 ]GRID grid.177174.3, ISNI 0000 0001 2242 4849, Department of Systems Life Sciences, Graduate School of Systems Life Sciences, , Kyushu University, ; Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan

[2 ]GRID grid.177174.3, ISNI 0000 0001 2242 4849, Department of Molecular Biology, Graduate School of Medical Sciences, , Kyushu University, ; Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan

[3 ]GRID grid.63906.3a, ISNI 0000 0004 0377 2305, Department of Systems BioMedicine, , National Research Institute for Child Health and Development, ; 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535 Japan

[4 ]GRID grid.177174.3, ISNI 0000 0001 2242 4849, Division of Bioinformatics, Medical Institute of Bioregulation, , Kyushu University, ; Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan

[5 ]GRID grid.177174.3, ISNI 0000 0001 2242 4849, Department of Anatomy and Cell Biology, Graduate School of Medical Sciences, , Kyushu University, ; Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan

[6 ]GRID grid.177174.3, ISNI 0000 0001 2242 4849, Division of Transcriptomics, Medical Institute of Bioregulation, , Kyushu University, ; Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan

Author information

Miki Inoue http://orcid.org/0000-0003-3581-9852

Kei Sugihara http://orcid.org/0000-0002-5502-6967

Shuji Takada http://orcid.org/0000-0002-9406-4683

Mikita Suyama http://orcid.org/0000-0001-9526-3193

Yasuyuki Ohkawa http://orcid.org/0000-0001-6440-9954

Article

Publisher ID: 3941

DOI: 10.1038/s42003-022-03941-5

PMC ID: 9478096

PubMed ID: 36109592

SO-VID: 13f4dac0-7c88-4641-9c41-e7b0f29ce2db

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 18 March 2022

Date accepted : 2 September 2022

Funding

Funded by: FundRef https://doi.org/10.13039/501100001691, MEXT | Japan Society for the Promotion of Science (JSPS);

Award ID: JP20K08863

Award ID: JP17H06427

Award ID: JP20H04935

Award ID: JP19H05244

Award ID: JP20H00456

Award ID: JP20H04846

Award ID: JP20K21398

Award ID: JP17H06427

Award ID: JP20H03436

Award Recipient : Takashi Baba Shuji Takada Yasuyuki Ohkawa Ken-ichirou Morohashi

Funded by: FundRef https://doi.org/10.13039/501100003382, MEXT | JST | Core Research for Evolutional Science and Technology (CREST);

Award ID: JPMJCR16G1

Award Recipient : Yasuyuki Ohkawa

Funded by: FundRef https://doi.org/10.13039/100009619, Japan Agency for Medical Research and Development (AMED);

Award ID: JP20ek0109489h0001

Award ID: JP20gk0210019

Award Recipient : Yasuyuki Ohkawa Ken-ichirou Morohashi

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Keywords: differentiation,cell signalling

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Keywords: differentiation, cell signalling

Tmsb10 triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway

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Most cited references 71

Fast gapped-read alignment with Bowtie 2.

HTSeq—a Python framework to work with high-throughput sequencing data

A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

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