Beclin-1-dependent autophagy, but not apoptosis, is critical for stem-cell-mediated endometrial programming and the establishment of pregnancy

Popli, Pooja; Tang, Suni; Chadchan, Sangappa B.; Talwar, Chandni; Guan, Xiaoming; Monsivais, Diana; Lydon, John P.; Stallings, Christina L.; Moley, Kelle H.; Kommagani, Ramakrishna

doi:10.1016/j.devcel.2023.03.013

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Ferroptosis Associated With Autophagy1

Histological Analysis1

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2023

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Cited by 8 publications

(2 citation statements)

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“…For example, BECN1 mediated by ELAVL1 can increase the phagocytosis of hepatic stellate cells [ 91 ]. Therefore, revealing the complex role of BECN1 in autophagy-dependent ferroptosis may depend on BECN1 recognizing more related proteins [ 96 , 97 ].…”

Section: Ferroptosis Associated With Autophagymentioning

confidence: 99%

Ferroptosis, autophagy, tumor and immunity

Xie,

Zhou,

Wang

et al. 2023

Heliyon

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Section: Ferroptosis Associated With Autophagymentioning

confidence: 99%

Ferroptosis, autophagy, tumor and immunity

Xie,

Zhou,

Wang

et al. 2023

Heliyon

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“…Sections (5 μm) were immunostained (n = 5 per group) (45). Briefly, after deparaffinization, sections were rehydrated in an ethanol gradient, then boiled for 20 min in citrate-buffer (Vector Laboratories Inc., CA, USA) for antigen retrieval.…”

Section: Histological Analysismentioning

confidence: 99%

SF3B1-dependent alternative splicing is critical for maintaining endometrial homeostasis and the establishment of pregnancy

Popli¹,

Chadchan²,

Dias

et al. 2023

Preprint

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The remarkable potential of human endometrium to undergo spontaneous remodeling is shaped by controlled spatiotemporal gene expression patterns. Although hormone-driven transcription shown to govern these patterns, the post-transcriptional processing of these mRNA transcripts, including the mRNA splicing in the endometrium is not studied yet. Here, we report that the splicing factor, SF3B1 is central in driving alternative splicing (AS) events that are vital for physiological responses of the endometrium. We show that loss of SF3B1 splicing activity impairs stromal cell decidualization as well as embryo implantation. Transcriptomic analysis revealed that SF3B1 depletion decidualizing stromal cells led to differential mRNA splicing. Specifically, a significant upregulation in mutually exclusive AS events (MXEs) with SF3B1 loss resulted in the generation of aberrant transcripts. Further, we found that some of these candidate genes phenocopy SF3B1 function in decidualization. Importantly, we identify progesterone as a potential upstream regulator of SF3B1-mediated functions in endometrium possibly via maintaining its persistently high levels, in coordination with deubiquitinating enzymes. Collectively, our data suggest that SF3B1-driven alternative splicing plays a critical role in mediating the endometrial-specific transcriptional paradigms. Thus, the identification of novel mRNA variants associated with successful pregnancy establishment may help to develop new strategies to diagnose or prevent early pregnancy loss.

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