
암 관련 대식세포에서 FABP4는 불포화 지방산 유도 지질 축적과 지방분해를 매개하여 유방암 전이를 촉진한다.


coremsg

A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown. Herein, we demonstrated that unsaturated fatty acids (FAs), unlike saturated ones, are more likely to form lipid droplets in macrophages. Specifically, unsaturated FAs, including linoleic acids (LA), activate the FABP4/CEBPα pathway, leading to triglyceride synthesis and lipid droplet formation. Furthermore, FABP4 enhances lipolysis and FA utilization by breast cancer cells, which promotes cancer cell migration in vitro and metastasis in vivo . Notably, a deficiency of FABP4 in macrophages significantly reduces LA-induced lipid metabolism. Therefore, our findings suggest FABP4 as a crucial lipid messenger that facilitates unsaturated FA-mediated lipid accumulation and lipolysis in TAMs, thus contributing to the metastasis of breast cancer.

![Figure][1]</img>

Highlights 

1.  Unlike saturated fatty acids, unsaturated fatty acids preferentially promote lipid droplet formation in macrophages.

2.  Unsaturated fatty acids activate the FABP4/CEBPα axis for neutral lipid biosynthesis in macrophages

3.  Deficiency of FABP4 compromised unsaturated fatty acid-mediated lipid accumulation and utilization in macrophages

4.  FABP4-mediated lipid metabolism in macrophages contributes to breast cancer metastasis

### Competing Interest Statement

The authors have declared no competing interest.

 [1]: pending:yes

FABP4-mediated lipid accumulation and lipolysis in tumor associated macrophages promote breast cancer metastasis

암-관련-대식세포에서-fabp4-매개-지질-축적-및-지방분해가-유방암-전이를-촉진한다


암 관련 대식세포에서 FABP4 매개 지질 축적 및 지방분해가 유방암 전이를 촉진한다


title_rewrite


세포 간 접착 강도 증가는 조직의 액체-고체 상전이를 유발하며, 이는 동적 불균질성과 유리질 동역학을 동반한다.


세포-간-접착이-조직-유동성-조절에-미치는-역할


세포 간 접착이 조직 유동성 조절에 미치는 역할



세포 내 소기관의 지속적인 분열과 융합 과정에서 발생하는 비평형 역학이 소기관의 형태와 운동을 결정한다.


활성-세포-내-소기관의-운송-경로에서의-형태-역학


활성 세포 내 소기관의 운송 경로에서의 형태 역학



내재화 과정에서 G 단백질은 엔도좀 막에 효율적으로 공급되지 않으며, 이는 세포 내 다양한 막 구획에서의 G 단백질 신호 전달에 영향을 미칠 수 있다.


Classical G protein-coupled receptor (GPCR) signaling takes place in response to extracellular stimuli and involves receptors and heterotrimeric G proteins located at the plasma membrane. It has recently been established that GPCR signaling can also take place from intracellular membrane compartments, including endosomes that contain internalized receptors and ligands. While the mechanisms of GPCR endocytosis are well understood, it is not clear how well internalized receptors are supplied with G proteins. To address this gap we use gene editing, confocal microscopy, and bioluminescence resonance energy transfer to study the distribution and trafficking of endogenous G proteins. We show here that constitutive endocytosis is sufficient to supply newly internalized endocytic vesicles with 20-30% of the G protein density found at the plasma membrane. We find that G proteins are present on early, late, and recycling endosomes, are abundant on lysosomes, but are virtually undetectable on the endoplasmic reticulum, mitochondria, and the medial Golgi apparatus. Receptor activation does not change heterotrimer abundance on endosomes. Our findings provide a subcellular map of endogenous G protein distribution, suggest that G proteins may be partially excluded from nascent endocytic vesicles, and are likely to have implications for GPCR signaling from endosomes and other intracellular compartments.

### Competing Interest Statement

The authors have declared no competing interest.

Visualization of endogenous G proteins on endosomes and other organelles

내재화-과정의-비효율성으로-인한-이종삼량체-g-단백질의-엔도좀-내-부족


내재화 과정의 비효율성으로 인한 이종삼량체 G 단백질의 엔도좀 내 부족



마우스 배아의 세포 극성화 시기가 비동기적이며, 이는 4세포기 이전부터 존재하는 세포 간 비대칭성과 관련이 있다. 조기 극성화 세포는 대칭적 세포 분열과 영양외배엽 세포 운명으로 편향된다.


The first lineage allocation in mouse and human embryos separates the inner cell mass (ICM) from the outer trophectoderm (TE). This symmetry breaking event is executed through polarization of cells at the 8-cell stage and subsequent asymmetric divisions, generating polar (TE) and apolar (ICM) cells. Here, we show that embryo polarization is unexpectedly asynchronous. Cells polarizing at the early and late 8-cell stage have distinct molecular and morphological properties that direct their following lineage specification, with early polarizing cells being biased towards producing the TE lineage. More recent studies have also implicated heterogeneities between cells prior to the 8-cell stage in the first lineage allocation: cells exhibiting reduced methyltransferase CARM1 activity at the 4-cell stage are predisposed towards the TE fate. Here, we demonstrate that reduced CARM1 activity and upregulation of its substrate BAF155 promote early polarization and TE specification. These findings provide a link between asymmetries at the 4-cell stage and polarization at the 8-cell stage, mechanisms of the first lineage allocation that had been considered separate.

### Competing Interest Statement

The authors have declared no competing interest.

Asynchronous mouse embryo polarization leads to heterogeneity in cell fate specification

마우스-배아의-비동기적-극성화로-인한-세포-운명-결정의-이질성


마우스 배아의 비동기적 극성화로 인한 세포 운명 결정의 이질성



세틴은 엑소시스트 복합체의 세포막 표적화를 직접적으로 조절하여 세포 분열 과정에서 외분비를 조절한다.


Septins can function as scaffolds for protein recruitment, membrane-bound diffusion barriers, or membrane curvature sensors. Septins are important for cytokinesis, but their exact roles are still obscure. In fission yeast, four septins (Spn1 to Spn4) accumulate at the rim of the division plane as rings. The octameric exocyst complex, which tethers exocytic vesicles to the plasma membrane, exhibits a similar localization and is essential for plasma membrane deposition during cytokinesis. Without septins, the exocyst spreads across the division plane but absent from the rim during septum formation. These results suggest that septins and the exocyst physically interact for proper localization. Indeed, we predicted six pairs of direct interactions between septin and exocyst subunits by AlphaFold2 ColabFold, most of them are confirmed by co-immunoprecipitation and yeast two-hybrid assays. Exocyst mislocalization results in mistargeting of secretory vesicles and their cargos, which leads to cell-separation delay in septin mutants. Our results indicate that septins guide the targeting of exocyst complex on the plasma membrane for vesicle tethering during cytokinesis through direct physical interactions.

### Competing Interest Statement

The authors have declared no competing interest.

*   Co-IP
    :   Co-immunoprecipitation
    EMCCD
    :   Electron-multiplying charge-coupled device
    FPS
    :   Frame per second
    FRAP
    :   Fluorescence recovery after photobleaching
    NA
    :   Numerical aperture
    PB
    :   Phloxin B
    pLDDT
    :   Predicted Local-Distance Difference Test
    ROI
    :   Region of interest
    SPB
    :   Spindle pole body
    TIRF
    :   Total internal reflection fluorescence
    TRAPP-II
    :   Transport particle protein-II
    WT
    :   Wild type

Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis

세포-분열-과정에서-세틴과-엑소시스트-복합체-간의-물리적-상호작용을-통한-외분비-기능


세포 분열 과정에서 세틴과 엑소시스트 복합체 간의 물리적 상호작용을 통한 외분비 기능



STAG3는 배아줄기세포에서 세포질 내 mRNA 조절을 통해 다능성 상태에서 벗어나는 데 중요한 역할을 한다.


STAG proteins are key regulators of the cohesin complex and are often linked to alterations in cell identity and disease. Among the mammalian STAG paralogs, STAG3 has been less extensively studied beyond its known roles in meiosis. In this work, we demonstrate that STAG3 is expressed in mouse embryonic stem cells (mESCs) and primordial germ cell-like cells (PGCLCs), where it is required for cell fate decisions. Distinct from the other STAG proteins, STAG3 mediates its effects in the cytoplasm, facilitating the post-transcriptional regulation of gene expression. Furthermore, STAG3 localises to the centrosome independently of cohesin and interacts with proteins involved in mRNA localisation and stability. The knockdown of STAG3 in mESCs using siRNAs results in the destabilisation of the centrosome and the key P-body RNA-induced silencing complex (RISC) component TNRC6C, leading to the derepression of P-body localised mRNAs, such as DPPA3. Our results propose a model in which STAG3 collaborates with RNA-binding proteins (RBPs) and specific target mRNAs to control post-transcriptional gene expression and facilitate the transition from pluripotency in mESCs. Given that STAG3 is upregulated in various cancers, our results provide a novel perspective on how STAG proteins might contribute to cell identity and disease.

### Competing Interest Statement

The authors have declared no competing interest.

STAG3 promotes exit from pluripotency through post-transcriptional mRNA regulation in the cytoplasm

배아줄기세포에서-stag3가-세포질-내-mrna-조절을-통해-다능성-탈출을-촉진한다-


배아줄기세포에서 STAG3가 세포질 내 mRNA 조절을 통해 다능성 탈출을 촉진한다.



Sox9 전사 인자는 각막 상피 줄기 세포의 비대칭적 세포 운명 전환에 필수적이며, 이를 통해 각막 상피 조직의 항상성을 유지한다.


Adult tissues with high cellular turnover require a balance between stem cell renewal and differentiation, yet the mechanisms underlying this equilibrium are unclear. The cornea exhibits a polarized lateral flow of progenitors from the peripheral stem cell niche to the center; attributed to differences in cellular fate. To identify genes that are critical for regulating the asymmetric fates of limbal stem cells and their transient amplified progeny in the central cornea, we utilized an in vivo cell cycle reporter to isolate proliferating basal cells across the anterior ocular surface epithelium and performed single-cell transcriptional analysis. This strategy greatly increased the resolution and revealed distinct basal cell identities with unique expression profiles of structural genes and transcription factors. We focused on Sox9; a transcription factor implicated in stem cell regulation across various organs. Sox9 was found to be differentially expressed between limbal stem cells and their progeny in the central corneal. Lineage tracing analysis confirmed that Sox9 marks long-lived limbal stem cells and conditional deletion led to abnormal differentiation and squamous metaplasia in the central cornea. These data suggest a requirement for Sox9 for the switch to asymmetric fate and commitment toward differentiation, as transient cells exit the limbal niche. By inhibiting terminal differentiation of corneal progenitors and forcing them into perpetual symmetric divisions, we replicated the Sox9 loss-of-function phenotype. Our findings reveal an essential role for Sox9 for the spatial regulation of asymmetric fate in the corneal epithelium that is required to sustain tissue homeostasis.

### Competing Interest Statement

The authors have declared no competing interest.

Sox9 marks limbal stem cells and is required for asymmetric cell fate switch in the corneal epithelium

각막-상피-세포의-비대칭적-세포-운명-전환을-조절하는-핵심-전사-인자-sox9


각막 상피 세포의 비대칭적 세포 운명 전환을 조절하는 핵심 전사 인자 Sox9



척추동물 분절 시계의 파형 패턴은 세포 내부의 자율적인 타이밍 메커니즘에 의해 구동된다. 이 메커니즘은 세포 분화와 연계되어 있으며, 외부 신호에 의해 조절된다.


Rhythmic and sequential segmentation of the growing vertebrate body relies on the segmentation clock, a multi-cellular oscillating genetic network. The clock is visible as tissue-level kinematic waves of gene expression that travel through the pre-somitic mesoderm (PSM) and arrest at the position of each forming segment. Here we test how this hallmark wave pattern is driven by culturing single maturing PSM cells. We compare their cell-autonomous oscillatory and arrest dynamics to those we observe in the embryo at cellular resolution, finding similarity in the relative slowing of oscillations and arrest in concert with differentiation. This shows that cell-extrinsic signals are not required by the cells to instruct the developmental program underlying the wave pattern. We show that a cell-autonomous timing activity initiates during cell exit from the tailbud, then runs down in the anterior-ward cell flow in the PSM, thereby using elapsed time to provide positional information to the clock. Exogenous FGF lengthens the duration of the cell-intrinsic timer, indicating extrinsic factors in the embryo may regulate the segmentation clock via the timer. In sum, our work suggests that a noisy cell-autonomous, intrinsic timer drives the slowing and arrest of oscillations underlying the wave pattern, while extrinsic factors in the embryo tune this timer’s duration and precision. This is a new insight into the balance of cell-intrinsic and -extrinsic mechanisms driving tissue patterning in development.

### Competing Interest Statement

Competing Interests: PS is a co-founder of Viventis Microscopy.

Cell-autonomous timing drives the vertebrate segmentation clock’s wave pattern

단일-세포-자율적-생성-파형-패턴-척추동물-분절-시계의-핵심-메커니즘


단일 세포 자율적 생성 파형 패턴: 척추동물 분절 시계의 핵심 메커니즘



IL-6 신호 전달은 건 조직의 수리 섬유아세포 활성화와 손상 부위로의 이동을 촉진하여 건 질환의 주요 특징을 악화시킨다.


Tendinopathies are debilitating diseases currently increasing in prevalence and associated costs. There is a need to deepen our understanding of the underlying cell signaling pathways to unlock effective treatments. In this work, we screen cell signaling pathways in human tendinopathies and find positively enriched IL-6/JAK/STAT signaling alongside signatures of cell populations typically activated by IL-6 in other tissues. In human tendinopathic tendons, we also confirm the strong presence and co-localization of IL-6, IL6R, and CD90, an established marker of reparative fibroblasts. To dissect the underlying causalities, we combine IL-6 knock-out mice with an explant-based assembloid model of tendon damage to successfully connect IL-6 signaling to reparative fibroblast activation and recruitment. Vice versa, we show that these reparative fibroblasts promote the development of tendinopathy hallmarks in the damaged explant upon IL-6 activation. We conclude that IL-6 activates tendon fibroblast populations which then initiate and deteriorate tendinopathy hallmarks.

### Competing Interest Statement

The authors have declared no competing interest.

IL-6 SIGNALING EXACERBATES HALLMARKS OF CHRONIC TENDON DISEASE BY STIMULATING REPARATIVE FIBROBLASTS

만성-건-질환의-주요-특징을-악화시키는-il-6-신호-전달-전구체-증식-및-손상-부위로의-이동-촉진


만성 건 질환의 주요 특징을 악화시키는 IL-6 신호 전달: 전구체 증식 및 손상 부위로의 이동 촉진
