Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis

Hong, Hyebeen; Lee, Jong-Eun; Park, Guk-Yeol; Kim, Soeun; Park, Ji-Ho; Song, Youngkwon; Kim, Tae Jin; Lee, You Jeong; Roh, Tae-Young; Kwok, Seung‐Ki; Kim, Sung Won; Tan, Qingrong

doi:10.1016/j.celrep.2022.110386

Cited by 9 publications

(12 citation statements)

References 69 publications

(88 reference statements)

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“…The BHLHE41 gene is located on human chromosome 12q12.1, which plays a critical role in modulating cell differentiation, apoptosis, hypoxia, and immune response [ 23 – 25 ]. Nagata et al found that BHLHE41 expression was lower in lung adenocarcinoma tissue than in normal lung tissue [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway

Chen

Dong

Wan

et al. 2022

Gastroenterology Research and Practice

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Objective. BHLHE41 has been shown to be a marker of tumorigenesis. Colon cancer (CC) is a common malignant tumor of colonic mucosa. This study mainly explored the mechanism of BHLHE41 in alleviating malignant behavior of hypoxia-induced CC cells. Methods. The levels of BHLHE41 in CC and normal cell lines were tested by Western blot and qRT-PCR. After, CC cells were subjected to hypoxia treatment and BHLHE41 overexpression transfection, and the BHLHE41 expression, the effect of BHLHE41 on CC cell viability, apoptosis, migration, and invasion and cell cycle were tested by qRT-PCR and relevant cell functional experiments. HIF-1α and epithelial-mesenchymal transition- (EMT-) related proteins were tested by Western blot. Moreover, CC tumor-bearing model was established in nude mice, and the effect of BHLHE41 on the tumor was evaluated by measuring the tumor volume and weight. Then, the expressions of BHLHE41 and EMT-related proteins were detected by immunohistochemistry and Western blot. Results. Western blot and qRT-PCR showed that BHLHE41 was lowly expressed in CC cells. BHLHE41 overexpression could inhibit the hypoxia-induced CC cell viability, migration, and invasion, induce apoptosis, and alter cell cycle. Besides, BHLHE41 overexpression could enhance the levels of E-cadherin but reduce the levels of HIF-1α, N-cadherin, vimentin, and MMP9 in hypoxia-induced CC cells. Moreover, BHLHE41 overexpression reduced tumor volume, weight, and EMT-related proteins levels in tumor tissues. Conclusions. BHLHE41 overexpression could mitigate the malignant behavior of hypoxia-induced CC via modulating the HIF-1α/EMT pathway.

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Section: Discussionmentioning

confidence: 99%

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway

Chen

Dong

Wan

et al. 2022

Gastroenterology Research and Practice

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“…shBhlhe41-1 was selected for the generation of the Bhlhe41-knockdown Cic f/f ;Cd19-Cre FL chimeric mice. The images were reproduced from our previous research article ( Hong et al., 2022 ). …”

Section: Before You Beginmentioning

confidence: 99%

“…The frequency and number of B-1a cells in Bhlhe41 −/− mice are significantly reduced compared to those in wild-type mice ( Kreslavsky et al., 2017 ). Capicua (CIC) is a high mobility group (HMG) box-containing transcriptional repressor that regulates lymphocyte development and differentiation ( Hong et al., 2022 ; Kim et al., 2021 ; Lee, 2020 ; Park et al., 2017 , 2019 , 2020 ). B-cell-specific Cic null ( Cic f/f ;Cd19-Cre ) mice exhibited expansion of the B-1a cell population ( Hong et al., 2022 ).…”

Section: Expected Outcomesmentioning

confidence: 99%

“…Capicua (CIC) is a high mobility group (HMG) box-containing transcriptional repressor that regulates lymphocyte development and differentiation ( Hong et al., 2022 ; Kim et al., 2021 ; Lee, 2020 ; Park et al., 2017 , 2019 , 2020 ). B-cell-specific Cic null ( Cic f/f ;Cd19-Cre ) mice exhibited expansion of the B-1a cell population ( Hong et al., 2022 ). In addition, BHLHE41 levels were significantly increased in splenic B cells from Cic f/f ;Cd19-Cre mice ( Hong et al., 2022 ).…”

Section: Expected Outcomesmentioning

confidence: 99%

“…B-cell-specific Cic null ( Cic f/f ;Cd19-Cre ) mice exhibited expansion of the B-1a cell population ( Hong et al., 2022 ). In addition, BHLHE41 levels were significantly increased in splenic B cells from Cic f/f ;Cd19-Cre mice ( Hong et al., 2022 ).…”

Section: Expected Outcomesmentioning

confidence: 99%

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Systems-level identification of key transcription factors in immune cell specification

Liu

Omilusik

Toma

et al. 2022

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SummaryTranscription factors (TFs) are crucial for regulating cell differentiation during the development of the immune system. However, the key TFs for orchestrating the specification of distinct immune cells are not fully understood. Here, we integrated the transcriptomic and epigenomic measurements in 73 mouse and 61 human primary cell types, respectively, that span the immune cell differentiation pathways. We constructed the cell-type-specific transcriptional regulatory network and assessed the global importance of TFs based on the Taiji framework, which is a method we have previously developed that can infer the global impact of TFs using integrated transcriptomic and epigenetic data. Integrative analysis across cell types revealed putative driver TFs in cell lineage-specific differentiation in both mouse and human systems. We have also identified TF combinations that play important roles in specific developmental stages. Furthermore, we validated the functions of predicted novel TFs in murine CD8+ T cell differentiation and showed the importance of Elf1 and Prdm9 in the effector versus memory T cell fate specification and Kdm2b and Tet3 in promoting differentiation of CD8+ tissue resident memory (Trm) cells, validating the approach. Thus, we have developed a bioinformatic approach that provides a global picture of the regulatory mechanisms that govern cellular differentiation in the immune system and aids the discovery of novel mechanisms in cell fate decisions.

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Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis

Cited by 9 publications

References 69 publications

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway

Generation of hematopoietic lineage cell-specific chimeric mice using retrovirus-transduced fetal liver cells

Systems-level identification of key transcription factors in immune cell specification

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