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Analysis of institutional authors

Acosta-Iborra BAuthorBerrouayel YAuthorDel Peso LAuthorJiménez BAuthor

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July 28, 2024
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Bhlhe40 Regulates Proliferation and Angiogenesis in Mouse Embryoid Bodies under Hypoxia.

Publicated to:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 25 (14): - 2024-07-12 25(14), DOI: 10.3390/ijms25147669

Authors: Acosta-Iborra B; Gil-Acero AI; Sanz-Gómez M; Berrouayel Y; Puente-Santamaría L; Alieva M; Del Peso L; Jiménez B

Affiliations

Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Arturo Duperier, 4, 28029 Madrid, Spain. - Author

Abstract

Knowledge of the molecular mechanisms that underlie the regulation of major adaptive responses to an unbalanced oxygen tension is central to understanding tissue homeostasis and disease. Hypoxia-inducible transcription factors (HIFs) coordinate changes in the transcriptome that control these adaptive responses. Here, we focused on the functional role of the transcriptional repressor basic-helix-loop-helix family member e40 (Bhlhe40), which we previously identified in a meta-analysis as one of the most consistently upregulated genes in response to hypoxia across various cell types. We investigated the role of Bhlhe40 in controlling proliferation and angiogenesis using a gene editing strategy in mouse embryonic stem cells (mESCs) that we differentiated in embryoid bodies (EBs). We observed that hypoxia-induced Bhlhe40 expression was compatible with the rapid proliferation of pluripotent mESCs under low oxygen tension. However, in EBs, hypoxia triggered a Bhlhe40-dependent cell cycle arrest in most progenitor cells and endothelial cells within vascular structures. Furthermore, Bhlhe40 knockout increased the basal vascularization of the EBs in normoxia and exacerbated the hypoxia-induced vascularization, supporting a novel role for Bhlhe40 as a negative regulator of blood vessel formation. Our findings implicate Bhlhe40 in mediating key functional adaptive responses to hypoxia, such as proliferation arrest and angiogenesis.

Keywords

AngiogenesisBhlhe40Embryoid bodiesHypoxiaProliferationVascular development

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 68/231, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Multidisciplinary.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-16:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 5 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

    It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

    • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

    Leadership analysis of institutional authors

    There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (ACOSTA IBORRA, MARIA BARBARA) and Last Author (JIMENEZ CUENCA, BENILDE).