Yeats4 drives ILC lineage commitment via activation of <i>Lmo4</i> transcription

Liu, Benyu; Yang, Liuliu; Zhu, Xiaoxiao; Li, Huimu; Zhu, Pingping; Wu, Jiayi; Lu, Tiankun; He, Luyun; Liu, Nian; Meng, Shu; Zhou, Liang; Ye, Buqing; Tian, Yong; Fan, Zusen

doi:10.1084/jem.20182363

Cited by 13 publications

(11 citation statements)

References 57 publications

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“…of the pro-oncogenic protein LMO4: Yeats4 recruits the Dot1l-RNA Pol II complex to the LMO4 promoter in innate lymphoid cells [48]. Our CHIP-seq and CHIP-qPCR data showed a similar pattern in breast cancer cells.…”

Section: Discussionsupporting

confidence: 57%

“…LMO4, a LIM-only transcriptional regulator, was reported to induce breast cancer invasion and predict poor outcomes [ 46 , 47 ]. Benyu Liu et al reported the mechanism underlying the activation of the pro-oncogenic protein LMO4: Yeats4 recruits the Dot1l–RNA Pol II complex to the LMO4 promoter in innate lymphoid cells [ 48 ]. Our CHIP-seq and CHIP-qPCR data showed a similar pattern in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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HNRNPU promotes the progression of triple-negative breast cancer via RNA transcription and alternative splicing mechanisms

Han

Liu

et al. 2022

Cell Death Dis

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Triple-negative breast cancer (TNBC) is a great detriment to women’s health due to the lack of effective therapeutic targets. In this study, we employed an integrated genetic screen to identify a pivotal oncogenic factor, heterogeneous nuclear ribonucleoprotein U (HNRNPU), which is required for the progression of TNBC. We elucidated the pro-oncogenic role of HNRNPU, which can induce the proliferation and migration of TNBC cells via its association with DEAD box helicase 5 (DDX5) protein. Elevated levels of the HNRNPU-DDX5 complex prohibited the intron retention of minichromosome maintenance protein 10 (MCM10) pre-mRNA, decreased nonsense-mediated mRNA decay, and activated Wnt/β-catenin signalling; on the other hand, HNRNPU-DDX5 is located in the transcriptional start sites (TSS) of LIM domain only protein 4 (LMO4) and its upregulation promoted the transcription of LMO4, consequently activating PI3K-Akt-mTOR signalling. Our data highlight the synergetic effects of HNRNPU in RNA transcription and splicing in regulating cancer progression and suggest that HNRNPU may act as a potential molecular target in the treatment of TNBC.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

HNRNPU promotes the progression of triple-negative breast cancer via RNA transcription and alternative splicing mechanisms

Han

Liu

et al. 2022

Cell Death Dis

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“…Consistent with our flow cytometry results, there is a clear developmental progression of CD34 + cells to more specified progenitors, which correspond with an increase in T-lineage transcription factors. A small cluster of less differentiated cells was present and marked by the expression of LMO4 , likely representing group 2 innate lymphoid cells (ILC2) 24 .…”

Section: Resultsmentioning

confidence: 99%

DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system

et al. 2021

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T cells are pivotal effectors of the immune system and can be harnessed as therapeutics for regenerative medicine and cancer immunotherapy. An unmet challenge in the field is the development of a clinically relevant system that is readily scalable to generate large numbers of T-lineage cells from hematopoietic stem/progenitor cells (HSPCs). Here, we report a stromal cell-free, microbead-based approach that supports the efficient in vitro development of both human progenitor T (proT) cells and T-lineage cells from CD34+cells sourced from cord blood, GCSF-mobilized peripheral blood, and pluripotent stem cells (PSCs). DL4-μbeads, along with lymphopoietic cytokines, induce an ordered sequence of differentiation from CD34+ cells to CD34+CD7+CD5+ proT cells to CD3+αβ T cells. Single-cell RNA sequencing of human PSC-derived proT cells reveals a transcriptional profile similar to the earliest thymocytes found in the embryonic and fetal thymus. Furthermore, the adoptive transfer of CD34+CD7+ proT cells into immunodeficient mice demonstrates efficient thymic engraftment and functional maturation of peripheral T cells. DL4-μbeads provide a simple and robust platform to both study human T cell development and facilitate the development of engineered T cell therapies from renewable sources.

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“…2B) (34). Rora, Icos, Thy1, and Lmo4 are highly expressed by ILC progenitors (9,(35)(36)(37). ROR and Lmo4 are involved in the ILC lineage commitment (27,35,37).…”

Section: Molecular Features Of Pilcps Versus Silcps For Differentiati...mentioning

confidence: 99%

“…Rora, Icos, Thy1, and Lmo4 are highly expressed by ILC progenitors (9,(35)(36)(37). ROR and Lmo4 are involved in the ILC lineage commitment (27,35,37). Top genes that were down-regulated in sILCPs compared with pILCPs included Bcl2, Actg1, several major histocompatibility complex II molecules (H2afy, H2-Ab1, H2-Q7, H2-Aa, and H2-Eb1), Cd74, Egr1, Nfkb1, and Itga4, among others (Fig.…”

Section: Molecular Features Of Pilcps Versus Silcps For Differentiati...mentioning

confidence: 99%

Identification of the niche and mobilization mechanism for tissue-protective multipotential bone marrow ILC progenitors

et al. 2022

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Innate lymphoid cells (ILCs) play crucial roles in maintenance and defense of peripheral tissues but would undergo natural and inflammation-induced attrition over time. A potential solution to counteract the peripheral ILC attrition would be regulated mobilization of bone marrow (BM) ILC progenitors. The major multipotential ILC progenitors (ILCPs) are divided into two subsets in distinct niches of the BM. Sinusoid ILCPs emigrate from the BM to circulate the peripheral blood. In contrast, parenchyma ILCPs are more likely in cell cycling and less likely to emigrate BM. The mobilization of BM ILCPs is internally and externally controlled by the coordinated expression of the BM retention receptors (Itg-α4 and CXCR4) and the emigration receptors sphingosine-1-phosphate (S1P) receptors. The expression of the BM retention and emigration receptors is developmentally regulated in the steady state and by the inflammasome-derived IL-18. Upon infusion, sinusoid ILCPs can effectively restore peripheral ILC insufficiency and tissue integrity during inflammatory responses.

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Yeats4 drives ILC lineage commitment via activation of Lmo4 transcription

Cited by 13 publications

References 57 publications

HNRNPU promotes the progression of triple-negative breast cancer via RNA transcription and alternative splicing mechanisms

HNRNPU promotes the progression of triple-negative breast cancer via RNA transcription and alternative splicing mechanisms

DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system

Identification of the niche and mobilization mechanism for tissue-protective multipotential bone marrow ILC progenitors

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