Article
Developmental Biology
Jiayi Tu, Shanshan Yu, Jingzhen Li, Mengmeng Ren, Yangjun Zhang, Jiong Luo, Kui Sun, Yuexia Lv, Yunqiao Han, Yuwen Huang, Xiang Ren, Tao Jiang, Zhaohui Tang, Mark Thomas Shaw Williams, Qunwei Lu, Mugen Liu
Summary: Mutations in Dhx38 lead to defects in chromosome alignment and apoptosis in EMPs and HSPCs, highlighting the importance of alternative splicing in hematopoiesis.
Article
Cell Biology
Wanbo Tang, Jian He, Tao Huang, Zhijie Bai, Chaojie Wang, Haizhen Wang, Ruichuang Yang, Yanli Ni, Jun Hou, Junliang Wang, Jie Zhou, Yingpeng Yao, Yandong Gong, Siyuan Hou, Bing Liu, Yu Lan
Summary: Using gene knockin strategy, a new Hlf-tdTomato reporter mouse model was developed that revealed the importance of Hlf expression in the generation of functional HSCs from early pre-HSCs. The construction of a novel Hlf-CreER mouse model enabled genetic lineage tracing showing the contribution of early cells to multi-lineage hematopoiesis in the bone marrow. This study provides valuable tools to specifically trace the fate of emerging HSCs during development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Fabian Klein, Julien Roux, Grozdan Cvijetic, Patrick Fernandes Rodrigues, Lilly von Muenchow, Ruth Lubin, Pawel Pelczar, Simon Yona, Panagiotis Tsapogas, Roxane Tussiwand
Summary: The study shows that an uncommitted precursor expressing TdT can generate a large fraction of myeloid and erythro-megakaryocyte cells. Developmental trajectories of hematopoietic stem cells towards different lineages are determined by intrinsic and extrinsic cues. The transient induction of TdT on MPPs reflects a transcriptionally dynamic but uncommitted stage, associated with multilineage differentiation potential.
Article
Developmental Biology
Laina Freyer, Yvan Lallemand, Pascal Dardenne, Alina Sommer, Anne Biton, Elisa Gomez Perdiguero
Summary: In this study, the researchers used flow cytometry and genetic labeling techniques to analyze the characteristics of placenta macrophages in mice. They identified fetal-derived HBCs and placenta-associated maternal macrophages and traced the ontogeny of HBCs. The findings suggest that HBCs originate from yolk sac-derived erythro-myeloid progenitors and may play an important role in fetoplacental vascular development and/or remodeling. The researchers also discovered that HBCs are dependent on the transcription factor Pu.1 and its loss-of-function affects the morphology of the placenta labyrinth.
Article
Oncology
Daimin Xiang, Mingye Gu, Junyu Liu, Wei Dong, Zhishi Yang, Kui Wang, Jing Fu, Hongyang Wang
Summary: This study found that hepatic leukemia factor (HLF) is aberrantly expressed in intrahepatic cholangiocarcinoma (ICC) and is associated with poor prognosis. Mechanistically, HLF activation in ICC is mediated by METTL3-dependent m6A methylation of the HLF mRNA. HLF promotes ICC cell self-renewal, tumorigenicity, proliferation, and metastasis through the activation of the WNT/β-catenin signaling pathway via its target genes.
Article
Medicine, Research & Experimental
Lakshmi Reddy Palam, Baskar Ramdas, Katelyn Pickerell, Santhosh Kumar Pasupuleti, Rahul Kanumuri, Annamaria Cesarano, Megan Szymanski, Bryce Selman, Utpal P. Dave, George Sandusky, Fabiana Perna, Sophie Paczesny, Reuben Kapur
Summary: Loss of function mutations in DNMT3A are commonly found in AML patients with normal cytogenetics and are associated with poor prognosis. In this study, we found that loss of Dnmt3a resulted in myeloproliferation and hyperactivation of the PI3K pathway. Treatment with PI3K inhibitors partially corrected myeloproliferation, with the alpha/beta inhibitor being more effective. Additionally, PI3K inhibitor treatment prolonged survival and reduced leukemic burden in a human DNMT3A mutant AML model.
Article
Multidisciplinary Sciences
Wen Hao Neo, Yiran Meng, Alba Rodriguez-Meira, Muhammad Z. H. Fadlullah, Christopher A. G. Booth, Emanuele Azzoni, Supat Thongjuea, Marella F. T. R. de Bruijn, Sten Eirik W. Jacobsen, Adam J. Mead, Georges Lacaud
Summary: The study reveals the crucial role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE. Loss of EZH2 activity in HE leads to the generation of non-functional EMPs due to a lack of Wnt signaling downregulation, while the generation of primitive erythroid cells is not affected. EZH2 is essential for the generation of functional EMPs at the onset of the endothelial-to-hematopoietic transition but becomes dispensable later on.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Trine A. Kristiansen, Qinyu Zhang, Stefano Vergani, Elena Boldrin, Niklas Krausse, Oscar Andre, Pontus Nordenfelt, Mikael Sigvardsson, David Bryder, Jonas Ungerbaeck, Joan Yuan
Summary: The fetal-to-adult switch in hematopoietic stem cell behavior is characterized by changes in lineage output and entry into deep quiescence. The emergence of megakaryocyte-biased HSCs coincides with this developmental switch. Molecular changes in HSCs during the fetal-to-adult transition include acquisition of megakaryocyte lineage priming signatures and increased amplitude of early megakaryocyte differentiation events. LIN28B, which promotes fetal-like self-renewal, acts as an insulator against the establishment of a megakaryocyte-biased HSC pool. The developmental regulation of megakaryocyte priming may represent a switch for HSCs to prioritize self-renewal in the fetus and increased host protection in postnatal life.
Article
Cell & Tissue Engineering
Zhiwen You, Luyue Wang, Hui He, Ziyan Wu, Xinyue Zhang, Shuaixiang Xue, Peibo Xu, Yanhong Hong, Man Xiong, Wu Wei, Yuejun Chen
Summary: Single-cell split barcoding (SISBAR) allows clonal tracking of single-cell transcriptomes across stages, revealing a multi-level clonal lineage landscape. The study shows that transcriptome-defined cell types can arise from distinct lineages, each with distinct molecular signatures.
Review
Biochemistry & Molecular Biology
Shokrollah Elahi
Summary: Under physiological conditions, HSPCs in the bone marrow niches are responsible for regulating hematopoiesis, but they can be influenced by microbial agents and infection-induced mediators. This article reviews the impact of these factors on hematopoiesis and discusses how SARS-CoV-2 infection alters the hematopoietic system, including lymphopenia, thrombocytopenia, and hypercoagulability.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Lu Cui, Ignacio Moraga, Tristan Lerbs, Camille Van Neste, Stephan Wilmes, Naotaka Tsutsumi, Aaron Claudius Trotman-Grant, Milica Gakovic, Sarah Andrews, Jason Gotlib, Spyros Darmanis, Martin Enge, Stephen Quake, Ian S. Hitchcock, Jacob Piehler, K. Christopher Garcia, Gerlinde Wernig
Summary: The study developed a series of surrogate protein ligands that can modulate TPO-R signaling, preserving HSC properties and inhibiting oncogenic signaling through TPO-R by tuning downstream responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Bo Yu, Bingyan Wu, Pingshan Hong, Huan Peng, Mengyun Zhang, Qi Zhang, Lijuan Liu, Xiaofei Liu, Yang Geng, Jinyong Wang, Yu Lan
Summary: This study reveals that the coordinated action of Runx1, Hoxa9, Hlf, and Hoxa7 leads to the generation of hematopoietic progenitor cells with the capacity for multilineage hematopoietic reconstitution.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: The origin cell of chronic myeloid leukemia is a hematopoietic stem cell and the hallmark oncogene is BCR-ABLp210, which influences hematopoietic stem and progenitor cells to myeloid fate. Studies have shown that BCR-ABLp210 affects the epigenome, leading to dysregulation of fate choice for hematopoietic stem cells, but the reason why neutrophils are abundantly produced in the disease remains unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Miner Xie, Shanshan Zhang, Fang Dong, Qingyun Zhang, Jinhong Wang, Chenchen Wang, Caiying Zhu, Sen Zhang, Bingqing Luo, Peng Wu, Hideo Ema
Summary: The study showed that G-CSF directly affected lymphoid-biased HSC but not myeloid-biased HSC. The results indicated that G-CSF can enhance the reconstitution level of lymphoid-biased HSC, but does not increase the frequency of myeloid-biased HSC.
Article
Cell & Tissue Engineering
Munetomo Takahashi, Melania Barile, Richard H. Chapple, Yu-jung Tseng, Daisuke Nakada, Katrin Busch, Ann-Kathrin Fanti, Petter Sawen, David Bryder, Thomas Hofer, Berthold Gottgens
Summary: This study reconciled in vivo flux experiments from different laboratories into a unified model using processed flow cytometry data and a biology-driven modeling approach, shedding light on the function of hematopoietic stem cells (HSCs). Comparative analysis revealed distinct labeling efficiencies of different transgenic models across a heterogeneous HSC pool, validated by marker gene expression associated with HSC function. Finally, the unified model of HSC differentiation was demonstrated to simulate clonal expansion in the early stages of leukemia.
Article
Hematology
Larisa Kovtonyuk, Francisco Caiado, Santiago Garcia-Martin, Eva-Maria Manz, Patrick Helbling, Hitoshi Takizawa, Steffen Boettcher, Fatima Al-Shahrour, Cesar Nombela-Arrieta, Emma Slack, Markus G. Manz
Summary: Aging is associated with impaired hematopoietic and immune function. Older mice produce more IL-1a/b and have higher levels of microbe-associated molecular patterns. HSC aging is driven by IL-1a/b, and blocking IL-1 signaling can reverse myeloid-biased output in older mice.
Article
Oncology
Seiko Yoshino, Miwa Tanaka, Yoshitaka Sunami, Tomoko Takahara, Yukari Yamazaki, Mizuki Homme, Akiko Niibori-Nambu, Motomi Osato, Takashi Minami, Keiichi Ishihara, Takuro Nakamura
Article
Anesthesiology
Tsunehisa Tsubokawa, Mizuyuki Nakamura, Erika Miyazaki, Yoshihiro Kimura, Yusuke Kashiwagi, Tomohiko Sato, Kotaro Kida
JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA
(2022)
Article
Hematology
Takeshi Hagino, Tomohiko Sato, Reina Saga, Hiroko Hidai, Yoshiro Murai, Hideki Akiyama, Sayuri Motomura
Summary: This case report highlights a transient myeloid leukemoid reaction in a patient with chronic myelomonocytic leukemia (CMML) following treatment with azacitidine (AZA). The leukocytosis observed was likely a differentiation response to the treatment and not a progression of CMML. Clinical monitoring and differential diagnosis are necessary in such cases.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2022)
Article
Infectious Diseases
Hiroto Ishii, Tomohiko Sato, Miyuki Ishibashi, Hiroki Yokoyama, Takeshi Saito, Tetsunori Tasaki, Shingo Yano
Summary: The first case of immune complex type hemolytic anemia caused by initial micafungin administration is reported. The patient, a 42-year-old Japanese man receiving chemotherapy for primary amyloidosis, was given micafungin as prophylaxis. Previous cases in the literature were associated with secondary administration and immune hemolytic attacks. This rare case highlights the need for increased awareness of micafungin-induced hemolytic anemia upon initial administration.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Biology
Yuta Koui, Takako Ideue, Michael Boylan, Matthew J. Anderson, Motomi Osato, Toshio Suda, Tomomasa Yokomizo, Yoh-suke Mukouyama
Summary: Recent studies have shown that vascular endothelial cells and pericytes in the developing brain have heterogeneous origins, contrary to classical experimental evidence suggesting a mesodermal origin. In this study, we conducted a genetic lineage tracing experiment and provided evidence that cephalic paraxial mesodermal cells give rise to endothelial cells and pericytes in the developing mouse brain. We discovered that Hepatic leukemia factor (Hlf) is transiently expressed in the cephalic paraxial mesenchyme during embryonic day 8.0-9.0, and the marked Hlf-expressing cells at E8.0 mainly contribute to the developing brain vasculature. Interestingly, the marked Hlf-expressing cells at E10.5, which were previously reported to contain embryonic hematopoietic stem cells, do not contribute to the vascular cells. Overall, our genetic lineage tracing data support the idea that transient expression of Hlf marks a cephalic paraxial mesenchyme population involved in the development of brain vasculature.
Article
Hematology
Yosuke Masamoto, Akira Chiba, Hideaki Mizuno, Toshiya Hino, Hiroki Hayashida, Tomohiko Sato, Masashige Bando, Katsuhiko Shirahige, Mineo Kurokawa
Summary: Aberrant expression of EVI1+ is associated with poor outcomes in AML. Evi1high KMT2A-MLLT1-transformed AML cells exhibit distinct features and resistance to chemotherapy. ERG and cyclin D1 play pivotal roles in the biology of EVI1+ AML, with ERG contributing to aggressive disease nature and chemoresistance, and cyclin D1 leading to IFN-gamma signature and exhausted T-cell phenotypes.
Article
Medicine, Research & Experimental
Xiaoxiao Liu, Naru Sato, Tomohiro Yabushita, Jingmei Li, Yuhan Jia, Moe Tamura, Shuhei Asada, Takeshi Fujino, Tsuyoshi Fukushima, Taishi Yonezawa, Yosuke Tanaka, Tomofusa Fukuyama, Akiho Tsuchiya, Shiori Shikata, Hiroyuki Iwamura, Chieko Kinouchi, Kensuke Komatsu, Satoshi Yamasaki, Tatsuhiro Shibata, Atsuo T. Sasaki, Janet Schibler, Mark Wunderlich, Eric O'Brien, Benjamin Mizukawa, James C. Mulloy, Yuki Sugiura, Hitoshi Takizawa, Takuma Shibata, Kensuke Miyake, Toshio Kitamura, Susumu Goyama
Summary: Inosine monophosphate dehydrogenase (IMPDH) inhibitors have been widely used as immunosuppressants but their antitumor effects remain unproven in clinical practice. This study demonstrated the susceptibility of acute myeloid leukemias (AMLs) with MLL-fusions to IMPDH inhibitors in vitro. Alternate-day administration of IMPDH inhibitors effectively suppressed the development of MLL-AF9-driven AML without compromising immune function. The antileukemia effect of IMPDH inhibitors was attributed to the overactivation of Toll-like receptor (TLR)-TRAF6-NF-kappa B signaling pathway and upregulation of VCAM1 adhesion molecule. Combined treatment with IMPDH inhibitors and TLR1/2 agonist showed a promising inhibitory effect on MLL-fusion AML. These findings provide a rational basis for clinical testing of IMPDH inhibitors against MLL-fusion AMLs and other aggressive tumors with active TLR signaling.
EMBO MOLECULAR MEDICINE
(2023)
Editorial Material
Oncology
Tsunenori Yamamoto, Ryouichi Tsunedomi, Masao Nakajima, Nobuaki Suzuki, Shin Yoshida, Shinobu Tomochika, Ming Xu, Yuki Nakagami, Hiroto Matsui, Yukio Tokumitsu, Yoshitaro Shindo, Yusaku Watanabe, Michihisa Iida, Shigeru Takeda, Shoichi Hazama, Tsuyoshi Tanabe, Tatsuya Ioka, Yoshinobu Hoshii, Akifumi Kiyota, Hitoshi Takizawa, Yutaka Kawakami, Tomio Ueno, Hiroaki Nagano
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Charlotte Flahou, Tatsuya Morishima, Natsumi Higashi, Yoshikazu Hayashi, Huaigeng Xu, Bo Wang, Chaoqi Zhang, Atsushi Ninomiya, Wei -Yin Qiu, Akinori Yuzuriha, Daisuke Suzuki, Sou Nakamura, Markus Manz, Shin Kaneko, Akitsu Hotta, Hitoshi Takizawa, Koji Eto, Naoshi Sugimoto
Summary: This study demonstrates that genetically depleted hiPSCs can be rejected by endogenous NK cells in humanized mice, suggesting the potential limitations of using HLA-edited cells. These findings contribute to the development of universal cell therapies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Hematology
Mohamed Gaber Abdallah, Vania Swee Imm Teoh, Bibek Dutta, Tomomasa Yokomizo, Motomi Osato
Summary: Cancer is rare at the cellular level but common at the body level, with one third of humans dying from it. A small subset of cells in the body have the features that allow genetic changes to induce cancer. By introducing RUNX1-ETO into childhood hematopoietic stem cells, we successfully induced AML with clinical features similar to human patients, suggesting that childhood HSCs constitute the permissive window for RUNX1-ETO leukemogenesis.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Miwa Tanaka, Mizuki Homme, Yasuyo Teramura, Kohei Kumegawa, Yukari Yamazaki, Kyoko Yamashita, Motomi Osato, Reo Maruyama, Takuro Nakamura
Summary: This study aimed to clarify the functional role of HEY1-NCOA2 in the development and progression of mesenchymal chondrosarcoma. They found that introducing HEY1-NCOA2 into mouse embryonic cells successfully induced subcutaneous tumors with biphasic morphologies and the expression of chondrogenic differentiation marker Sox9. The interaction between HEY1-NCOA2 and Runx2 was observed, and treatment with the HDAC inhibitor panobinostat suppressed tumor growth both in vitro and in vivo.
Article
Biochemistry & Molecular Biology
Yuxin Wang, Tatsuya Morishima, Maiko Sezaki, Ryo Sato, Gaku Nakato, Shinji Fukuda, Kouji Kobiyama, Ken J. Ishii, Yuhua Li, Hitoshi Takizawa
Summary: Bacterial infections can activate hematopoietic stem and progenitor cells to migrate from the bone marrow to the spleen, a process known as extramedullary hematopoiesis. Recent studies have shown that gut commensal bacteria not only regulate the host immune system, but also hematopoietic homeostasis. This study reveals that Akkermansia muciniphila, a mucin-degrading bacterium, can rapidly activate bone marrow myelopoiesis and induce delayed extramedullary hematopoiesis through the MYD88/TRIF innate immune signaling pathway.
Letter
Medicine, General & Internal
Koji Takahashi, Tomohiko Sato, Toshiyuki Ikeda
Summary: The WHiTE 5 trial results showed that elderly patients with hip fracture who underwent cemented hemiarthroplasty had higher postoperative health-related quality of life and lower risk of periprosthetic fracture compared to those who underwent uncemented hemiarthroplasty. However, there is a concern that postoperative delirium may have influenced the assessment of quality of life in this population, particularly at early follow-up.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Multidisciplinary Sciences
Yosuke Tanaka, Reina Takeda, Tsuyoshi Fukushima, Keiko Mikami, Shun Tsuchiya, Moe Tamura, Keito Adachi, Terumasa Umemoto, Shuhei Asada, Naoki Watanabe, Soji Morishita, Misa Imai, Masayoshi Nagata, Marito Araki, Hitoshi Takizawa, Tomofusa Fukuyama, Chrystelle Lamagna, Esteban S. Masuda, Ryoji Ito, Susumu Goyama, Norio Komatsu, Tomoiku Takaku, Toshio Kitamura
Summary: Leukemia stem cells in chronic myeloid leukemia are resistant to imatinib, but can be eliminated by combining imatinib with IRAK1/4 inhibitors that inhibit the IRAK1/4-NF-kappa B-PD-L1 signaling pathway.
NATURE COMMUNICATIONS
(2022)
