PXD023979

PXD023979 is an original dataset announced via ProteomeXchange.

Title	EGR4-dependent decrease of UTF1 is associated with failure to reserve spermatogonial stem cells in infertile men
Description	Despite the high incidence of male infertility, about 70% of infertile men do not receive a causative diagnosis. To gain insights into the regulatory mechanisms governing human germ cell function in normal and impaired spermatogenesis (crypto group), we combined single cell RNA sequencing (>30.000 cells), proteome, and histomorphometric analyses of testicular tissues. We found major alterations in the crypto spermatogonial compartment with increased numbers of the most undifferentiated spermatogonia (PIWIL4+ State 0 cells). We also observed a transcriptional switch within the spermatogonial compartment driven by the increased and prolonged expression of the transcription factor EGR4. Intriguingly, EGR4-regulated genes included the chromatin-associated transcriptional repressor UTF1, which was downregulated. Histomorphometrical analyses showed that these transcriptional changes were mirrored at the protein level and accompanied by a change in the chromatin structure of spermatogonia. This resulted in a reduction of Adark spermatogonia - characterized by tightly compacted chromatin and serving as reserve stem cells. These findings suggest that crypto patients are at a disadvantage especially in cases of gonadotoxic damage as they have less cells to help repopulate the testis. We hypothesize that the more relaxed chromatin status of spermatogonia is dependent on decreased UTF1 expression caused by EGR4 activation. These identified regulators of the spermatogonial compartment will be highly interesting targets to uncover genetic causes of male infertility.
HostingRepository	PRIDE
AnnounceDate	2021-11-02
AnnouncementXML	Submission_2021-11-02_03:43:00.400.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hannes Drexler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-03 09:02:54	ID requested
⏵ 1	2021-11-02 03:43:01	announced

Di Persio S, Tekath T, Siebert-Kuss LM, Cremers JF, Wistuba J, Li X, Meyer Zu H, ö, rste G, Drexler HCA, Wyrwoll MJ, T, ü, ttelmann F, Dugas M, Kliesch S, Schlatt S, Laurentino S, Neuhaus N, Single-cell RNA-seq unravels alterations of the human spermatogonial stem cell compartment in patients with impaired spermatogenesis. Cell Rep Med, 2(9):100395(2021) [pubmed]

submitter keyword: Male germline stem cells, spermatogonial stem cells, male infertility, impaired spermatogenesis, single cell RNA sequencing, human spermatogenesis, stem cell differentiation, testis, mass spectrometry, proteomics

Hannes C. A. Drexler
contact affiliation	Max Planck Institute for Molecular Biomedicine Bioanalytical Mass Spectrometry Röntgenstr. 20 48149 Münster Germany
contact email	hannes.drexler@mpi-muenster.mpg.de
lab head
Hannes Drexler
contact affiliation	Bioanalytical Mass Spectrometry
contact email	hannes.drexler@mpi-muenster.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/11/PXD023979

PRIDE project URI

• PRIDE
  1. PXD023979
     1. Label: PRIDE project
     2. Name: EGR4-dependent decrease of UTF1 is associated with failure to reserve spermatogonial stem cells in infertile men