Article
Multidisciplinary Sciences
Yeojin Lee, Emily DiMaulo-Milk, Juliana Leslie, Lei Ding
Summary: This study reveals that hematopoietic stem cells in the developing liver transition from intrinsic LIN28B-dependent maintenance to extrinsic TPO-dependent maintenance over time. Deletion of TPO reduces mTOR activity, induces differentiation gene expression, and preferentially depletes metabolically active stem cells.
Article
Multidisciplinary Sciences
Lijian Shao, Na Yoon Paik, Mark A. Sanborn, Thilinie Bandara, Anjali Vijaykumar, Kilian Sottoriva, Jalees Rehman, Cesar Nombela-Arrieta, Kostandin V. Pajcini
Summary: Notch signaling is crucial for the emergence and development of definitive hematopoietic stem cells (HSCs) in the embryo and fetal liver. This study reveals endothelial Jagged1 (Jag1) as a critical factor in early fetal liver vascular development but not essential for fetal HSC expansion. Jag1 is expressed in various hematopoietic cells in the fetal liver, including HSCs, but lost in adult bone marrow HSCs. Deletion of hematopoietic Jag1 does not impact fetal liver development, but results in a significant transplantation defect in fetal liver HSCs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Faith Andres, Natalie J. Hannan, Susan P. Walker, Teresa M. MacDonald, Georgia P. Wong, Ciara Murphy, Ping Cannon, Manju Kandel, Joshua Masci, Tuong-Vi Nguyen, Alison Abboud, Danica Idzes, Valerie Kyritsis, Natasha Pritchard, Stephen Tong, Tuuhevaha J. Kaituu-Lino
Summary: This study found that EPCR levels were significantly increased in both the placenta and circulation of patients with preterm preeclampsia and fetal growth restriction. Hypoxia may be associated with the elevation of placental EPCR. These findings have important implications for understanding the mechanisms underlying these conditions.
Article
Immunology
Anais Wanet, Mahmoud A. Bassal, Sweta B. Patel, Francisco Marchi, Samanta A. Mariani, Nouraiz Ahmed, Haoran Zhang, Marta Borchiellini, Sisi Chen, Junyan Zhang, Annalisa Di Ruscio, Kensuke Miyake, Mindy Tsai, Anuya Paranjape, Shin-Young Park, Hajime Karasuyama, Timm Schroeder, Elaine Dzierzak, Stephen J. Galli, Daniel G. Tenen, Robert S. Welner
Summary: E-cadherin expression in the hematopoietic system was studied using single-cell RNA-sequencing analyses and immunophenotyping. High levels of E-cadherin were found in progenitors within the granulocyte-monocyte progenitors (GMPs) fraction, with an enriched capacity to differentiate into basophils and mast cells. The transcriptional priming of these progenitors to the basophil and mast cell lineages was observed, with GATA-2 directly regulating E-cadherin expression in these lineages.
SCIENCE IMMUNOLOGY
(2021)
Article
Rheumatology
Meilang Xue, Haiyan Lin, Hai Po Helena Liang, Lara Bereza-Malcolm, Tom Lynch, Premarani Sinnathurai, Hartmut Weiler, Christopher Jackson, Lyn March
Summary: This study found that the deficiency of EPCR can ameliorate the onset and development of CIA by inhibiting the activation and migration of pathogenic Th cells and DCs. Therefore, targeting EPCR may constitute a novel strategy for future RA treatment.
Article
Hematology
Huimin Cao, Shalin H. Naik, Daniela Amann-Zalcenstein, Peter Hickey, Agus Salim, Benjamin Cao, Susan K. Nilsson, M. Cristina Keightley, Graham J. Lieschke
Summary: This study identifies the crucial role of the ZBTB11 transcription factor in definitive hematopoiesis. Deletion of ZBTB11 in mice leads to embryonic death and hematopoietic failure. Loss of ZBTB11 results in overspecification of hematopoietic stem cells, loss of stemness, impaired differentiation, and cell cycle regulation. This study highlights the cell-intrinsic requirement of ZBTB11 in maintaining a pool of maturation-capable HSCs and progenitor cells.
Review
Gastroenterology & Hepatology
Jeremy Lotto, Tabea L. Stephan, Pamela A. Hoodless
Summary: Advancements in single-cell technologies and lineage tracing have enhanced our understanding of liver development. This review explores the formation of different types of liver cells and highlights the similarities between early liver development and the pathogenesis of liver injury. The research has significantly advanced our knowledge of cell differentiation, fate decisions, and the signaling microenvironment in liver development. This understanding also provides insights into liver disease and cancer and offers potential for improving regenerative medicine strategies.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Cell Biology
Yanfang Lu, Miao Liu, Jennifer Yang, Sherman M. Weissman, Xinghua Pan, Samuel G. Katz, Siyuan Wang
Summary: This study investigates the spatial organization and transcriptional profile of individual cells in WT and Tet2(-/-) fetal livers, revealing that specific cell types are preferentially positioned next to each other and HSCs are in direct contact with ECs. Loss of Tet2 increases HSC number and upregulates Wnt and Notch signaling genes in the HSC niche, highlighting the contribution of distinct cell types to the regulation of HSC spatial organization in fetal liver.
Article
Developmental Biology
Dawn S. Lin, Andreas Trumpp
Summary: Endothelial protein C receptor (EPCR) is a reliable surface marker for identifying and isolating hematopoietic stem cells (HSCs). This study provides a comprehensive characterization of EPCR expression in HSCs and multipotent progenitor cells (MPPs) during normal and aged hematopoiesis, revealing higher expression in certain MPP subsets and aging-related expansion in HSCs.
CELLS & DEVELOPMENT
(2023)
Article
Multidisciplinary Sciences
Annie S. P. Yang, Devanjali Dutta, Kai Kretzschmar, Delilah Hendriks, Jens Puschhof, Huili Hu, Kim E. Boonekamp, Youri van Waardenburg, Susana M. Chuva de Sousa Lopes, Geert-Jan van Gemert, Johannes H. W. de Wilt, Teun Bousema, Hans Clevers, Robert W. Sauerwein
Summary: Researchers have found that hepatocytes derived from human hepatocyte organoids (HepOrgs) can support the development of Plasmodium falciparum, and have identified the importance of the host factor scavenger receptor B1 (SRB1) in parasite development.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Elena Erausquin, Maria Moran-Garrido, Jorge Saiz, Coral Barbas, Gilda Dichiara-Rodriguez, Alejandro Urdiciain, Jacinto Lopez-Sagaseta
Summary: Studies have shown that the nature of lipids bound to the endothelial cell protein C receptor (EPCR) is diverse, including phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositols, phosphatidylserines, ceramides, and sphingomyelins, which may impact its properties in anticoagulation and the onset of autoimmune disease.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Christina M. Termini, Amara Pang, Tiancheng Fang, Martina Roos, Vivian Y. Chang, Yurun Zhang, Nicollette J. Setiawan, Lia Signaevskaia, Michelle Li, Mindy M. Kim, Orel Tabibi, Paulina K. Lin, Joshua P. Sasine, Avradip Chatterjee, Ramachandran Murali, Heather A. Himburg, John P. Chute
Summary: Ionizing radiation and chemotherapy deplete hematopoietic stem cells and damage the vascular niche, leading to the secretion of SEMA3A from bone marrow endothelial cells. Inhibition of NRP1 promotes vascular and hematopoietic regeneration through increased expression of R spondin 2, suggesting a potential therapeutic target for improving hematopoietic recovery after myeloablation.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Makiko Mochizuki-Kashio, Noriko Otsuki, Kota Fujiki, Sherif Abdelhamd, Peter Kurre, Markus Grompe, Atsushi Iwama, Kayoko Saito, Ayako Nakamura-Ishizu
Summary: Fanconi Anemia (FA) is a genetic bone marrow failure disorder commonly diagnosed in school age children. Mitochondrial metabolism and mitophagy play important roles in long-term hematopoietic stem cell (HSC) function. Impaired mitophagy has been observed in FA cells. This study found that replication stress (RS) activates mitochondrial metabolism and mitophagy in HSC, and that FL HSCs deficient in FANCD2 show increased mitochondrial metabolism and mitophagy while adult FANCD2-deficient BM HSCs exhibit decreased mitophagy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell & Tissue Engineering
Jesus Maria Gomez-Salinero, Franco Izzo, Yang Lin, Sean Houghton, Tomer Itkin, Fuqiang Geng, Yaron Bram, Robert P. Adelson, Tyler M. Lu, Giorgio Inghirami, Jenny Zhaoying Xiang, Raphael Lis, David Redmond, Ryan Schreiner, Sina Y. Rabbany, Dan A. Landau, Robert E. Schwartz, Shahin Rafii
Summary: The heterogeneity of hepatic vascular cells during mouse development was studied through functional and single-cell RNA sequencing. It was found that the acquisition of sinusoidal endothelial cell identity starts during early development and is completed postnatally, with c-Maf playing a critical role in this process.
Article
Multidisciplinary Sciences
Runfeng Miao, Harim Chun, Xing Feng, Ana Cordeiro Gomes, Jungmin Choi, Joao P. Pereira
Summary: This study reveals that a complex homeostatic balance between hematopoietic stem cells (HSCs) and hematopoietic progenitor cells is maintained through competition for a limited amount of cell signaling molecule. When early hematopoietic progenitors fail to interact with specific cells, HSC numbers increase.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Subramaniam Agatheeswaran, Soumen Chakraborty
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2016)
Article
Oncology
Nivedita Kuila, Kasturi Bala Nayak, Arundhati Halder, Subramaniam Agatheeswaran, Ghanashyam Biswas, Sutapa Biswas, Naresh Chandra Pattnayak, Soumen Chakraborty
LEUKEMIA & LYMPHOMA
(2017)
Article
Cell Biology
Karolina Komorowska, Alexander Doyle, Martin Wahlestedt, Agatheeswaran Subramaniam, Shubhranshu Debnath, Jun Chen, Shamit Soneji, Ben Van Handel, Hanna K. A. Mikkola, Kenichi Miharada, David Bryder, Jonas Larsson, Mattias Magnusson
Article
Hematology
Mehrnaz Safaee Talkhoncheh, Agatheeswaran Subramaniam, Mattias Magnusson, Praveen Kumar, Jonas Larsson, Aurelie Baudet
Article
Hematology
Mehrnaz Safaee Talkhoncheh, Agatheeswaran Subramaniam, Mattias Magnusson, Praveen Kumar, Jonas Larsson, Aurelie Baudet
Letter
Hematology
Agatheeswaran Subramaniam, Mehrnaz Safaee Talkhoncheh, Mattias Magnusson, Jonas Larsson
Article
Biochemistry & Molecular Biology
S. Rajashree Nandagopalan, Subramaniam Agatheeswaran, Yellamandayya Vadlamudi, Sutapa Biswas, Ghanshyam Biswas, Naresh Chandra Pattnayak, Soumen Chakraborty
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2019)
Article
Hematology
Agatheeswaran Subramaniam, Kristijonas Zemaitis, Mehrnaz Safaee Talkhoncheh, David Yudovich, Alexandra Backstrom, Shubhranshu Debnath, Jun Chen, Mayur Vilas Jain, Roman Galeev, Massimiliano Gaetani, Roman A. Zubarev, Jonas Larsson
Article
Multidisciplinary Sciences
Ludwig Schmiderer, Agatheeswaran Subramaniam, Kristijonas Zemaitis, Alexandra Backstrom, David Yudovich, Svetlana Soboleva, Roman Galeev, Christelle N. Prinz, Jonas Larsson, Martin Hjort
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
David Yudovich, Alexandra Backstrom, Ludwig Schmiderer, Kristijonas Zemaitis, Agatheeswaran Subramaniam, Jonas Larsson
SCIENTIFIC REPORTS
(2020)
Article
Hematology
Kristijonas Zemaitis, Agatheeswaran Subramaniam, Roman Galeev, Aurel Prosz, Maria Jassinskaja, Jenny Hansson, Jonas Larsson
Summary: MTA1 has been identified as a negative regulator of human hematopoietic stem and progenitor cells (HSPCs) both in vitro and in vivo, playing critical roles in self-renewal and differentiation commitment.
EXPERIMENTAL HEMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kristijonas Zemaitis, Sudip Ghosh, Jenny Hansson, Agatheeswaran Subramaniam
Summary: Chemically modulating the ubiquitin-proteasome system for targeted protein degradation is a promising therapeutic approach. In this study, we found that the small molecule UM171, known for its support of hematopoietic stem cell propagation, targets members of the CoREST complex for degradation. Through proteomics analysis, we identified additional target proteins and determined the critical sites within their ELM2 domains necessary for UM171-mediated degradation. These findings provide important insights into the therapeutic potential of UM171 in a clinical context.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Hematology
Anna Rydstrom, Tan H. M. Grahn, Abhishek Niroula, Els Mansell, Mark van der Garde, Maroulio Pertesi, Agatheeswaran Subramaniam, Shamit Soneji, Roman Zubarev, Tariq Enver, Bjorn Nilsson, Kenichi Miharada, Jonas Larsson, Stefan Karlssona
Summary: This study provides a detailed functional and molecular characterization of HSCs at different phases of regeneration and identifies a gene set associated with the transition from proliferation to quiescence.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Hematology
Praveen Kumar, Dominik Beck, Roman Galeev, Julie A. I. Thoms, Mehrnaz Safaee Talkhoncheh, Ineke de Jong, Ashwin Unnikrishnan, Aurelie Baudet, Agatheeswaran Subramaniam, John E. Pimanda, Jonas Larsson
