Article
Medicine, Research & Experimental
Yandan Chen, Shuyi Fang, Qingwei Ding, Rongzhen Jiang, Jiefeng He, Qin Wang, Yuting Jin, Xinxin Huang, Sheng Liu, Maegan L. Capitano, Thao Trinh, Yincheng Teng, Qingyou Meng, Jun Wan, Hal E. Broxmeyer, Bin Guo
Summary: The study found that under ex vivo culturing conditions, HSCs with low levels of mitochondrial ROS were enriched in the CD34+CD133+ADGRG1+ CB cell population. These cells showed increased mitochondrial oxidative stress in transcriptomic and metabolic profiling, along with loss of stemness.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Shuxian Dong, Qian Wang, Yun-Ruei Kao, Antonio Diaz, Inmaculada Tasset, Susmita Kaushik, Victor Thiruthuvanathan, Aliona Zintiridou, Edward Nieves, Monika Dzieciatkowska, Julie A. Reisz, Evripidis Gavathiotis, Angelo D'Alessandro, Britta Will, Maria Cuervo
Summary: Activation of hematopoietic stem cells involves molecular adaptations, with Chaperone-Mediated Autophagy (CMA) playing a role in sustaining HSC function and declining with age. Restoring old HSC functionality through CMA activation suggests it may be a promising therapeutic target for conditions like aging or stem-cell transplantation.
Article
Multidisciplinary Sciences
Claire Fielding, Andres Garcia-Garcia, Claudia Korn, Stephen Gadomski, Zijian Fang, Juan L. Reguera, Jose A. Perez-Simon, Berthold Gottgens, Simon Mendez-Ferrer
Summary: Cholinergic signals in the bone marrow preserve haematopoietic stem cell quiescence and self-renewal under proliferative stress.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Yavor K. Bozhilov, Ian Hsu, Elizabeth J. Brown, Adam C. Wilkinson
Summary: The haematopoietic system is crucial for our health and survival, consisting of various mature blood and immune cell types that support homeostasis. In vitro culture systems have been developed to expand and differentiate haematopoietic stem and progenitor cells, providing models for studying human haematopoiesis. These systems also have potential applications in transplantation and transfusion medicine.
Article
Cell & Tissue Engineering
Miriama Kruta, Mary Jean Sunshine, Bernadette A. Chua, Yunpeng Fu, Ashu Chawla, Christopher H. Dillingham, Lorena Hidalgo San Jose, Bijou De Jong, Fanny J. Zhou, Robert A. J. Signer
Summary: Maintaining proteostasis is crucial for preserving stem cell function, but mechanisms regulating proteostasis during stress in stem cells and its contribution to stem cell aging need further exploration. Activation of Hsf1 with small molecules can partially suppress protein synthesis, rebalance proteostasis, and support the regenerative activity of HSCs, indicating that Hsf1 promotes proteostasis and regenerative capacity in response to stress and aging.
Article
Biochemistry & Molecular Biology
Qihao Sun, Yiran Zhou, Minghao Xiong, Yuying Chen, Wen-Song Tan, Haibo Cai
Summary: The study identified MEK1 as a potential regulator of HSPC proliferation and demonstrated that the MEK1 agonist PAF C-16 can increase the numbers of HSPC and induce cell cycling. This expansion strategy enhances the clonal formation ability and secondary expansion capacity of HSPC compared to the control. The findings provide insights into regulating HSPC proliferation and cell production for transplantation.
CELL BIOCHEMISTRY AND FUNCTION
(2022)
Article
Cell Biology
Dehao Huang, Qianhao Zhao, Mengyun Zhang, Qitong Weng, Qi Zhang, Kaitao Wang, Fang Dong, Hui Cheng, Fangxiao Hu, Jinyong Wang
Summary: In this study, the researchers used a mouse model with conditional expression of Hoxb5 to investigate its effect on multipotent blood progenitor cells. They found that induced expression of Hoxb5 in these cells led to the generation of a new cell type that can repopulate long-term multilineage haematopoiesis. RNA-seq analysis showed that these cells exhibited features of DNA replication and cell division.
CELL PROLIFERATION
(2022)
Review
Pediatrics
Katharina Kleinschmidt, Meng Lv, Asaf Yanir, Julia Palma, Peter Lang, Matthias Eyrich
Summary: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potential curative option for high-risk or refractory/relapsed leukemias in children, with haploidentical HSCT (hHSCT) showing significant advantages but posing the key question of how to deplete donor T-cells effectively. In vivo T-cell suppression and ex vivo T-cell depletion are two established methods to reduce alloreactivity in hHSCT, with different protocols utilizing post-transplantation cyclophosphamide or anti-thymocyte globulin. Studies have not shown a clear benefit for any specific method in terms of overall survival, non-relapse mortality, or disease recurrence.
FRONTIERS IN PEDIATRICS
(2021)
Article
Cell & Tissue Engineering
Zhidong Zhao, Yuxing Wang, Qian Wang, Jiawu Liang, Wei Hu, Sen Zhao, Peilin Li, Heng Zhu, Zhongli Li
Summary: The study found that r-ESW can promote the self-renewal of SCB-SPCs in vitro by targeting YAP activity and enhance its repair efficiency in vivo, indicating promising application prospects.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Cell Biology
Elliott J. Hagedorn, Julie R. Perlin, Rebecca J. Freeman, Samuel J. Wattrus, Tianxiao Han, Clara Mao, Ji Wook Kim, Ines Fernandez-Maestre, Madeleine L. Daily, Christopher D'Amato, Michael J. Fairchild, Raquel Riquelme, Brian Li, Dana A. V. E. Ragoonanan, Khaliun Enkhbayar, Emily L. Henault, Helen G. Wang, Shelby E. Redfield, Samantha H. Collins, Asher Lichtig, Song Yang, Yi Zhou, Balvir Kunar, Jesus Maria Gomez-Salinero, Thanh T. Dinh, Junliang Pan, Karoline Holler, Henry A. Feldman, Eugene C. Butcher, Alexander van Oudenaarden, Shahin Rafii, J. Philipp Junker, Leonard I. Zon
Summary: This study identifies a unique gene expression signature and regulatory landscape in sinusoidal endothelial cells within the hematopoietic stem and progenitor cell (HSPC) niche. By manipulating enhancers and transcription factors, the researchers reveal a transcriptional code that induces ectopic niche endothelial cells that support the recruitment, maintenance, and division of HSPCs. These findings provide insights for generating synthetic HSPC niches and developing therapies to modulate the endogenous niche.
DEVELOPMENTAL CELL
(2023)
Article
Cell Biology
Joey J. Ghersi, Gabriel Baldissera, Jared Hintzen, Stephanie A. Luff, Siyuan Cheng, Ivan Fan Xia, Christopher M. Sturgeon, Stefania Nicoli
Summary: Ghersi et al. have found that the diversity of haematopoietic stem and progenitor cells is established at the haemogenic endothelium level and is regulated by microRNA-128-mediated modulation of Wnt and Notch signalling. Haematopoietic stem and progenitor cells (HSPCs) generate different lineages and are produced in the embryo through the transformation of haemogenic endothelial cells in the aorta-gonad-mesonephros (AGM). The researchers discovered that loss of microRNA-128 leads to an expansion of HSPCs in the AGM with different cell cycle states and a bias towards erythroid and lymphoid progenitors.
NATURE CELL BIOLOGY
(2023)
Article
Cell & Tissue Engineering
Sudan Puri, Isabel Y. Moreno, Mingxia Sun, Sudhir Verma, Xiao Lin, Tarsis F. Gesteira, Vivien J. Coulson-Thomas
Summary: This study found that a hyaluronan (HA) matrix is present in the niche surrounding limbal epithelial stem cells (LESCs) during ex vivo expansion. The presence of both endogenous and exogenous HA was shown to help maintain the LESC phenotype and enhance proliferation, colony formation, and expression of stem cell markers. These findings suggest that HA could be a cost-effective substrate or supplement for culturing LESCs in clinical settings.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Multidisciplinary Sciences
Joachim Hanna, Flavio Beke, Louise M. O'Brien, Chrysa Kapeni, Hung-Chang Chen, Valentina Carbonaro, Alexander B. Kim, Kamal Kishore, Timon E. Adolph, Mikkel-Ole Skjoedt, Karsten Skjoedt, Marc de la Roche, Maike de la Roche
Summary: The study implicates Hedgehog signaling in Th17 polarization and intestinal immunopathology, suggesting the potential therapeutic use of Hedgehog inhibitors in the treatment of inflammatory bowel disease.
NATURE COMMUNICATIONS
(2022)
Article
Cell & Tissue Engineering
Marina Arjona, Armon Goshayeshi, Cristina Rodriguez-Mateo, Jamie O. Brett, Pieter Both, Heather Ishak, Thomas A. Rando
Summary: By using TubA, the quiescent state of MuSCs can be maintained ex vivo and their therapeutic potential can be enhanced.
Review
Biochemistry & Molecular Biology
Christina Bogensperger, Julia Hofmann, Franka Messner, Thomas Resch, Andras Meszaros, Benno Cardini, Annemarie Weissenbacher, Rupert Oberhuber, Jakob Troppmair, Dietmar ofner, Stefan Schneeberger, Theresa Hautz
Summary: Transplantation is limited by the shortage of healthy donor organs, but ex situ machine perfusion has the potential to expand the donor pool. Mesenchymal stem cells are considered as a tool with the potential to improve organs, but clinical benefits have not been conclusively demonstrated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Toshiya Nishimura, Fabian P. Suchy, Joydeep Bhadury, Kyomi J. Igarashi, Carsten T. Charlesworth, Hiromitsu Nakauchi
Summary: The deletion of Igf1r in mouse embryos creates a permissive cell-competitive niche in multiple organs, significantly increasing both mouse intraspecies and mouse/rat interspecies donor chimerism.
Article
Genetics & Heredity
Saumya Gupta, Denis L. Lafontaine, Sebastien Vigneau, Asia Mendelevich, Svetlana Vinogradova, Kyomi J. Igarashi, Andrew Bortvin, Clara F. Alves-Pereira, Anwesha Nag, Alexander A. Gimelbrant
Summary: In addition to X-chromosome inactivation and imprinting, monoallelic autosomal expression (MAE) is another mode of gene regulation in mammals. MAE is maintained through DNA methylation, and in some genes, DNA demethylation does not affect allelic imbalance.
G3-GENES GENOMES GENETICS
(2022)
Article
Hematology
Kyomi J. Igarashi, Iwo Kucinski, Yan Yi Chan, Tze-Kai Tan, Hwei Minn Khoo, David Kealy, Joydeep Bhadury, Ian Hsu, Pui Yan Ho, Kouta Niizuma, John W. Hickey, Garry P. Nolan, Katherine S. Bridge, Agnieszka Czechowicz, Berthold Gottgens, Hiromitsu Nakauchi, Adam C. Wilkinson
Summary: Hematopoietic stem cells (HSCs) are rare cells that can regenerate the blood and immune system. Allogeneic HSC transplantation (HSCT) is a curative therapy for hematolymphoid diseases, but it carries risks. This study demonstrates that using physioxic culture conditions can improve the selectivity of polyvinyl alcohol (PVA)-based HSC cultures. They also show that HSC-selective ex vivo cultures can remove GVHD-causing T cells and can be combined with genotoxic-free antibody-based conditioning HSCT approaches.
Article
Hematology
Juan A. Rubio-Lara, Kyomi J. Igarashi, Shubhankar Sood, Alban Johansson, Pia Sommerkamp, Masayuki Yamashita, Dawn S. Lin
Summary: Hematopoietic stem cells (HSCs) are crucial for the production of mature blood and immune cells. Ex vivo culture methods are essential for studying HSC biology and improving HSC therapies. This review discusses recent advances and technical considerations for three ex vivo HSC expansion methods.
EXPERIMENTAL HEMATOLOGY
(2023)
