Review
Cell Biology
Bai Ling, Yunyang Xu, Siyuan Qian, Ze Xiang, Shihai Xuan, Jian Wu
Summary: Hematopoietic stem cells (HSCs) play a crucial role in the hematopoietic system as they can self-renew and differentiate into various blood cells. The mTOR signaling pathway is an important regulator of HSCs' differentiation, self-renewal, and quiescence, and several molecules can modulate these potentials by influencing this pathway. This review discusses the regulation of HSCs' three potentials by the mTOR signaling pathway and highlights potential regulators. Additionally, the clinical significance of studying this regulation and future predictions are also outlined.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Nikolaos Doumpas, Simon Soderholm, Smarth Narula, Steven Moreira, Bradley W. Doble, Claudio Cantu, Konrad Basler
Summary: The study demonstrates that genetic deletion of TCF/LEF transcription factors allows mESCs to self-renew in N2B27 medium independently of specific chemical inhibitors, possibly through the regulation of genes such as Aire, Dnmt3l, and IcosL. TCF/LEF are shown to regulate specific genes in a beta-catenin independent manner, influencing the pluripotent state of mESCs.
Review
Oncology
Isabella Maria Mayer, Andrea Hoelbl-Kovacic, Veronika Sexl, Eszter Doma
Summary: Transplantation of adult hematopoietic stem cells is crucial for treating hematological disorders, while leukemic stem cells play a significant role in disease initiation and relapse. Understanding methods to maintain and expand hematopoietic cells, as well as isolate and enrich hematopoietic stem cells and leukemic stem cells, is essential for developing therapeutic strategies.
Article
Oncology
Ling Chen, Yanxia Liu, Yanning Xu, Said M. Afify, Ang Gao, Juan Du, Bingbing Liu, Xiaoying Fu, Yixin Liu, Ting Yan, Zhengmao Zhu, Masaharu Seno
Summary: In this study, it was discovered that the up-regulation of Dsg2 expression during the conversion of miPSCs into CSCs activates the Wnt/beta-catenin signaling pathway, implying a potential mechanism for the transformation of stem cells into a malignant phenotype.
EXPERIMENTAL CELL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Jiajia Wang, Xichen Wan, Qihua Le
Summary: SOX9, a member of the SRY-related HMG-box transcription factors, plays a critical role in fetal development and stem cell homeostasis. The interactions between SOX9 and the canonical Wnt signalling pathway are involved in various physiological and pathological processes of stem cells, including organ development, stem cell proliferation, differentiation, and tumorigenesis. This review summarizes the molecular mechanism of cross-interactions between SOX9 and the canonical Wnt signalling pathway, outlines its regulatory effects on homeostasis in different types of stem cells, and explores its potential in translational stem cell therapy.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Oncology
Yukai Lu, Lijing Yang, Mingqiang Shen, Zihao Zhang, Song Wang, Fang Chen, Naicheng Chen, Yang Xu, Hao Zeng, Mo Chen, Shilei Chen, Fengchao Wang, Mengjia Hu, Junping Wang
Summary: This study reveals that Tespa1 is important for the maintenance of hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) and plays a crucial role in HSC and LSC self-renewal. Tespa1 prevents degradation of c-Myc protein in HSCs and is essential for AML cell growth. Tespa1 deficiency suppresses leukemogenesis and LSC maintenance.
Review
Oncology
Stefan Koch
Summary: This article discusses the control of the Wnt pathway by FOX proteins, and the contribution of their interaction to cancer initiation and progression. Further research on FOX biology may lead to new targeted treatments for cancer.
Article
Cell & Tissue Engineering
Hao Yu, Rui Gao, Sisi Chen, Xicheng Liu, Qiang Wang, Wenjie Cai, Sasidhar Vemula, Aidan C. Fahey, Danielle Henley, Michihiro Kobayashi, Stephen Z. Liu, Zhijian Qian, Reuben Kapur, Hal E. Broxmeyer, Zhonghua Gao, Rongwen Xi, Yan Liu
Summary: Bmi1 is identified as a novel regulator of the Wnt signaling pathway in HSPCs, repressing Wnt gene expression and impacting HSC self-renewal and differentiation. Modulating Wnt signaling may hold potential for enhancing HSC transplantation outcomes.
STEM CELL REVIEWS AND REPORTS
(2021)
Article
Cell Biology
Qian Lan, Jiadong Cao, Xueting Bi, Xin Xiao, Dongsheng Li, Yilong Ai
Summary: This study suggests that using Cur-PDLSC-EV as a curcumin carrier can promote osteogenic differentiation of periodontal ligament stem cells, providing potential therapeutic value for periodontal diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Hong-Chen Yan, Yu Sun, Ming-Yu Zhang, Shu-Er Zhang, Jia-Dong Sun, Paul W. Dyce, Francesca Gioia Klinger, Massimo De Felici, Wei Shen, Shun-Feng Cheng
Summary: The study revealed that YAP activation by LPC promotes pluripotency of pSDSCs and inhibits their transdifferentiation into pPGCLCs. YAP maintains pluripotency of pSDSCs by upregulating Oct4 and Sox2, and regulates their fate through the Wnt/β-catenin signaling pathway.
HISTOCHEMISTRY AND CELL BIOLOGY
(2022)
Article
Cell Biology
Laura E. Sanman, Ina W. Chen, Jake M. Bieber, Veronica Steri, Coralie Trentesaux, Byron Hann, Ophir D. Klein, Lani F. Wu, Steven J. Altschuler
Summary: By investigating the responses of intestinal epithelium to different signaling pathways, it was found that modulation of transit-amplifying cell proliferation can change the ratio of differentiated cell types, highlighting the important role of transit-amplifying cells in tuning differentiated cell-type composition.
DEVELOPMENTAL CELL
(2021)
Article
Cell Biology
William Grey, Ana Rio-Machin, Pedro Casado, Eva Gronroos, Sara Ali, Juho J. Miettinen, Findlay Bewicke-Copley, Alun Parsons, Caroline A. Heckman, Charles Swanton, Pedro R. Cutillas, John Gribben, Jude Fitzgibbon, Dominique Bonnet
Summary: This study found that CKS1-dependent protein degradation plays a key role in eliminating tumor stem cells and reducing chemotherapeutic toxicity, while protecting normal hematopoietic stem cells in acute myeloid leukemia. These findings are of great significance for understanding the key vulnerability in malignant stem cell biology.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Ellen Youngsoo Rim, Hans Clevers, Roel Nusse
Summary: The Wnt pathway plays a central role in developmental and disease-related processes, regulating the generation and spatial arrangement of different cell types. Through regulation of cell fate, mitotic activity, and cell polarity, Wnt signaling coordinates development and tissue homeostasis, and its dysregulation is implicated in various disorders. This review summarizes the advances in our understanding of this pathway, from Wnt protein production to signal transduction in receiving cells. The evolutionary history of this pathway, as well as its regulators, and the remaining gaps in knowledge are discussed, highlighting directions for future research.
ANNUAL REVIEW OF BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mingliang He, Xiaoyang Lv, Xiukai Cao, Zehu Yuan, Tesfaye Getachew, Yutao Li, Shanhe Wang, Wei Sun
Summary: SRY-box transcription factor 18 (SOX18) is expressed in dermal papilla cells (DPCs) of sheep hair follicles and plays a crucial role in promoting DPC proliferation through activating the Wnt/β-Catenin signaling pathway. Inhibition of the Wnt/β-Catenin signaling pathway can be rescued by SOX18, suggesting the essential role of SOX18 in governing DPC proliferation and hair growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell & Tissue Engineering
Anna Bigas, Luis Galan Palma, Gayathri M. Kartha, Alessandra Giorgetti
Summary: Researchers have been studying embryonic stem cells for several decades, aiming to use them in regenerative medicine. The hematopoietic field has been a pioneer in utilizing stem cells for blood cell development and clinical applications. However, generating authentic hematopoietic stem cells has proven to be challenging. While progress has been made in understanding the origin of these cells during embryonic development, reproducing this process in the lab is still not possible. Nevertheless, knowledge gained from studying embryonic development is being applied to pluripotent stem cells derived from mice and humans. Additionally, studies have shown that hematopoietic cells derived from embryonic stem cells can recapitulate some leukemic transformation processes, making them valuable for modeling prenatal leukemia development and other leukemia-predisposing syndromes.
STEM CELLS TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Young-Kwon Park, Ji-Eun Lee, Zhijiang Yan, Kaitlin McKernan, Tommy O'Haren, Weidong Wang, Weiqun Peng, Kai Ge
Summary: The study reveals that BAF and MLL4 are interdependent in promoting enhancer activation by lineage-determining transcription factors during adipogenesis, providing a positive feedback mechanism for the activation of cell type-specific enhancers.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Shawn P. Fahl, Alejandra Contreras, Anjali Verma, Xiang Qiu, Christelle Harly, Freddy Radtke, Juan Carlos Zuniga-Pflucker, Cornelis Murre, Hai-Hui Xue, Jyoti Misra Sen, David L. Wiest
Summary: This study reveals a regulatory axis where T cell receptor (TCR) signaling controls TCF1 expression, which in turn regulates gamma delta T lineage commitment and effector fate. The level of TCF1 expression plays a critical role in setting the threshold for gamma delta T lineage commitment and modulating effector fate.
Article
Immunology
Qiang Shan, Shengen Shawn Hu, Shaoqi Zhu, Xia Chen, Vladimir P. Badovinac, Weiqun Peng, Chongzhi Zang, Hai-Hui Xue
Summary: Xue and colleagues demonstrate that the transcription factor Tcf1 plays a vital role in preprogramming the transcriptional program of CD8(+) central memory T cells, providing the necessary bioenergetic and proliferative support during secondary challenges. Tcf1 is required for the generation of secondary effector CD8(+) T cells and pathogen clearance during recall responses. Additionally, Tcf1 mediates extensive chromatin interactions and facilitates the induction of important genes in recall-stimulated CD8(+) T-CM cells.
Article
Multidisciplinary Sciences
Qiang Shan, Xiang Li, Xia Chen, Zhouhao Zeng, Shaoqi Zhu, Kexin Gai, Weiqun Peng, Hai-Hui Xue
Summary: The study demonstrates that Tcf1 and Lef1 play a crucial role in maintaining CD8(+) T cell identity by regulating three-dimensional genome organization and preventing aberrant expression of lineage-inappropriate genes.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Isaac J. Jensen, Xiang Li, Patrick W. McGonagill, Qiang Shan, Micaela G. Fosdick, Mikaela M. Tremblay, Jon Cd Houtman, Hai-Hui Xue, Thomas S. Griffith, Weiqun Peng, Vladimir P. Badovinac
Summary: The study found that sepsis leads to a reduction in memory CD8 T cells, but surviving cells proliferate quickly, especially a subpopulation called central memory CD8 T cells, thereby changing the overall composition of the memory CD8 T cell pool. This increased proliferation results in long-term changes in the quantity and composition of immune cells, potentially affecting the host's ability to respond to re-infection.
Correction
Immunology
Qiang Shan, Shengen Shawn Hu, Shaoqi Zhu, Xia Chen, Vladimir P. Badovinac, Weiqun Peng, Chongzhi Zang, Hai-Hui Xue
Article
Immunology
Qiang Shan, Shaoqi Zhu, Xia Chen, Jia Liu, Shuang Yuan, Xiang Li, Weiqun Peng, Hai-Hui Xue
Summary: The study demonstrates that Tcf1 and Lef1 recruit the genome organizer CTCF to promote chromatin interactions and form highly connected, dynamic interaction hubs in CD8(+) T cells undergoing homeostatic proliferation.
Review
Immunology
Xin Zhao, Shaoqi Zhu, Weiqun Peng, Hai-Hui Xue
Summary: T cells play a crucial role in defending against pathogens and malignant cells, and their development and differentiation rely on precise gene regulation. Higher-order genome organization, including chromatin loops and topologically associating domains, controls T cell gene expression. Recent studies have highlighted the role of transcription factors and CTCF in shaping chromatin architecture. This article summarizes current knowledge on the dynamic changes in genome topology during T cell development and function, providing a foundation for understanding the causal link between chromatin configuration and T cell transcriptional and functional outputs.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Jia Liu, Shaoqi Zhu, Wei Hu, Xin Zhao, Qiang Shan, Weiqun Peng, Hai-Hui Xue
Summary: Xue, Peng, and colleagues used multiomics approaches including Hi-C to demonstrate that CTCF promotes cytotoxic effector differentiation through dynamic redistribution, local chromatin accessibility control, and higher-order genomic reorganization, while enclosing memory precursor-associated genes within insulated neighborhoods to restrain their activation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Yunchen Wu, Yudan He, Chen Liu, Charlotte Ehle, Aishwarya Iyer-Bierhoff, Bing Liu, Thorsten Heinzel, Shaojun Xing
Summary: Sepsis is a life-threatening condition caused by excessive inflammation in response to an infection. Histone deacetylase inhibitors (HDACi) have been suggested as potential anti-inflammatory agents for sepsis treatment. In this study, the effects of SAHA, a HDACi, were investigated in a mouse model of endotoxemia. The results showed reduced inflammation and improved survival rates in mice, possibly through the inhibition of LDHA activity and inflammasome activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Xudong Zhao, Qiang Shan, Hai-Hui Xue
Summary: TCF1 plays essential roles in early T cell development and exhibits versatile, context-dependent functions in mature T cells. It is required for the self-renewal of stem-like CD8(+) T cells and regulates T cell responses effectively.
NATURE REVIEWS IMMUNOLOGY
(2022)