Article
Cell & Tissue Engineering
Ning Wang, Chuxin Chen, Yang Cheng, Yingjie Fu, Zhiyong Zhong, Yu Yang, Ling Lv, Honglin Chen, Jian Huang, Yuyou Duan
Summary: This study demonstrates that hypoxia can promote the differentiation of human embryonic stem cells into T lineage hematopoietic stem/progenitor cells. The activation of HIF-1 alpha signaling pathway, which upregulates arterial endothelial gene DLL4 and NOTCH1, plays an important role in this process. These findings provide a significant approach for the in vitro and in vivo production of fully functional hematopoietic stem/progenitor cells from hESCs.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Cell & Tissue Engineering
J. Philip Creamer, Stephanie A. Luff, Hao Yu, Christopher M. Sturgeon
Summary: The expression of CDX4+CD1d+ marks an early progenitor of hematopoietic endothelium with intra-embryonic-like potential in early mesoderm, providing important insights for the study of human hematopoietic development and potential improvements in hematopoietic differentiation conditions for regenerative medicine applications.
STEM CELL RESEARCH
(2022)
Article
Biology
Chaojie Wang, Yandong Gong, Anbang Wei, Tao Huang, Siyuan Hou, Junjie Du, Zongcheng Li, Junliang Wang, Bing Liu, Yu Lan
Summary: This study identified molecularly different endothelial cell populations in the yolk sac during midgestation and explored their hemogenic potential. It was found that these endothelial cell populations exhibited early lymphoid potential during embryonic development, with differences in characteristics and functions observed among endothelial cells from different vascular beds.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Review
Immunology
Serge A. van de Pavert
Summary: The ILC family, a recently described immune cell family, is involved in innate immune responses and tissue homeostasis. LTi cells, part of the ILC3 family, play a critical role in embryonic lymph node formation. Recent studies have provided insights into the origin of ILCs, including embryonic LTi cells being replaced by HSC derived progenitors in adults. This review focuses on the layered origin of the ILC3 family with an emphasis on the LTi cell lineage.
IMMUNOLOGICAL REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Serge A. van de Pavert
Summary: Innate Lymphoid Cells (ILC) play crucial roles in maintaining homeostasis and immunity, with their characteristics depending on tissue residency. Lymphoid Tissue inducer (LTi) cells are essential for embryonic lymph node formation and are also found in the embryonic gut. Recent studies have provided more insights into the origin and differentiation of these cells in embryos.
BIOMEDICAL JOURNAL
(2021)
Article
Multidisciplinary Sciences
Jun Shen, Yingxi Xu, Shuo Zhang, Shuzhen Lyu, Yingying Huo, Yaoyao Zhu, Kejing Tang, Junli Mou, Xinjie Li, Dixie L. Hoyle, Min Wang, Jianxiang Wang, Xin Li, Zack Z. Wang, Tao Cheng
Summary: This study used single-cell transcriptomic analysis to explore hematopoietic differentiation of human pluripotent stem cells and found that hypoxic conditions during differentiation promoted the generation of functional T cells, which inhibited tumor growth in vitro and in vivo. This represents a significant advancement in guiding the generation of functional T cells for clinical applications.
Article
Hematology
Yiqing Yang, Melanie Mumau, Joanna Tober, Qin Zhu, Laura Bennett, Courtney Hong, Derek Sung, Thomas Keller, Yasin Uzun, Peng Gao, Swapnil Shewale, Mei Chen, Jisheng Yang, Xiaowen Chen, Steven A. Thomas, Kai Tan, Nancy A. Speck, Mark L. Kahn
Summary: This study identifies the MEKK3-KLF2/4 signaling pathway as essential for the specification of hemogenic endothelial cells and their transition to intraaortic hematopoietic cluster cells during embryonic hematopoiesis. Inflammatory mediators and fluid shear forces can activate this signaling pathway and promote the process.
Article
Multidisciplinary Sciences
Norika Liu, Naofumi Kawahira, Yasuhiro Nakashima, Haruko Nakano, Akiyasu Iwase, Yasunobu Uchijima, Mei Wang, Sean M. Wu, Susumu Minamisawa, Hiroki Kurihara, Atsushi Nakano
Summary: This study reveals that the Nkx2-5/Notch/RA signaling pathway is crucial for macrophage differentiation and that a subset of endocardial cells gives rise to hematopoietic cells, which are important for the formation of cardiac valves.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Tanvi Sinha, Kelly Lammerts van Bueren, Diane E. Dickel, Ivana Zlatanova, Reuben Thomas, Carlos O. Lizama, Shan-Mei Xu, Ann C. Zovein, Kohta Ikegami, Ivan P. Moskowitz, Katherine S. Pollard, Len A. Pennacchio, Brian L. Black
Summary: This study investigates the initiation of gene-regulatory networks (GRNs) for endothelial and erythropoietic development by analyzing a hypomorphic Etv2 mutant. The researchers find that Etv2 has different threshold requirements for initiating the downstream GRNs for each lineage, directly regulating the endothelial GRN and indirectly activating Tal1 for erythropoietic development.
Article
Medicine, Research & Experimental
Kirsten Cante-Barrett, Mariska T. Meijer, Valentina Cordo, Rico Hagelaar, Wentao Yang, Jiyang Yu, Willem K. Smits, Marloes E. Nulle, Joris P. Jansen, Rob Pieters, Jun J. Yang, Jody J. Haigh, Steven Goossens, Jules P. P. Meijerink
Summary: This study found that elevated MEF2C expression is associated with ETP-ALL and blocks T cell differentiation while promoting the B-lineage program. MEF2C activates a B cell transcriptional program and enhances cell survival. Inhibiting SIK can alleviate the T cell developmental block and enhance sensitivity to prednisolone treatment.
Article
Cell Biology
Ho Sun Jung, Gene Uenishi, Mi Ae Park, Peng Liu, Kran Suknuntha, Matthew Raymond, Yoon Jung Choi, James A. Thomson, Irene M. Ong, Igor I. Slukvin
Summary: The research findings suggest that SOX17 is a key regulator in linking arterial and HOXA programs in hemogenic endothelium (HE) in humans, playing a crucial role in the specification of HE with robust lympho-myeloid potential. This understanding may contribute to better programming of hematopoietic stem cell fate from human pluripotent stem cells.
Article
Cell & Tissue Engineering
Yongqin Li, Jianyi Ding, Daisuke Araki, Jizhong Zou, Andre Larochelle
Summary: Researchers optimized the differentiation of induced pluripotent stem cells into hematopoietic stem and progenitor cells by modulating specific signaling pathways, resulting in increased self-renewal and multilineage differentiation potential.
Article
Biology
Sophie G. Kellaway, Peter Keane, Benjamin Edginton-White, Kakkad Regha, Ella Kennett, Constanze Bonifer
Summary: Mutations of the hematopoietic master regulator RUNX1 are associated with various hematological malignancies, with different types of mutations affecting endogenous RUNX1 function in unique ways. By comparing integrated phenotypic, transcriptomic, and genomic data, it was found that each class of mutant RUNX1 deregulates endogenous RUNX1 function through different mechanisms, resulting in specific alterations in gene regulatory network changes underlying blood cell development. This highlights the need for individual consideration in developing novel treatments for RUNX1-driven diseases.
LIFE SCIENCE ALLIANCE
(2021)
Article
Cell & Tissue Engineering
Soo-Been Jeon, A-Reum Han, Yoo Bin Choi, Ah Reum Lee, Ji Yoon Lee
Summary: This study successfully generated lymphoid lineage 78 T cells from human pluripotent stem cells under defined culture conditions, revealing an initial step in differentiating 78 T cells and its significance in cancer biology.
INTERNATIONAL JOURNAL OF STEM CELLS
(2022)
Article
Cell Biology
Shuo Zhang, Kengyuan Qu, Shuzhen Lyu, Dixie L. Hoyle, Cory Smith, Linzhao Cheng, Tao Cheng, Jun Shen, Zack Z. Wang
Summary: This study identified PEAR1 as a novel regulator of early hematopoietic development in human pluripotent stem cells, affecting endothelial-to-hematopoietic transition. PEAR1(+) cells exhibited greater hematopoietic capacity on endothelial niche, while PEAR1(-) cells did not. PEAR1 knockout impaired hematopoietic differentiation and expression of hematopoietic-related transcription factors. These findings highlight the importance of PEAR1 in balancing intrinsic and extrinsic signals for early hematopoietic fate decision.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Hematology
Saritha S. D'Souza, Sarah Bennett, Akhilesh Kumar, Laurel E. Kelnhofer, Jason Weinfurter, Kran Suknuntha, Jennifer Coonen, Andres Mejia, Heather Simmons, Thaddeus Golos, Peiman Hematti, Christian M. Capitini, Matthew R. Reynolds, Igor I. Slukvin
Summary: This study evaluated the outcomes of T-cell receptor alpha/beta-depleted alloHSCT in MHC-identical MCMs, finding that posttransplant treatment with cyclophosphamide and tacrolimus resulted in engraftment without GvHD in some animals, with long-term engraftment observed in one.
EXPERIMENTAL HEMATOLOGY
(2021)
Article
Cell Biology
Ho Sun Jung, Gene Uenishi, Mi Ae Park, Peng Liu, Kran Suknuntha, Matthew Raymond, Yoon Jung Choi, James A. Thomson, Irene M. Ong, Igor I. Slukvin
Summary: The research findings suggest that SOX17 is a key regulator in linking arterial and HOXA programs in hemogenic endothelium (HE) in humans, playing a crucial role in the specification of HE with robust lympho-myeloid potential. This understanding may contribute to better programming of hematopoietic stem cell fate from human pluripotent stem cells.
Article
Cell & Tissue Engineering
Kannan Manian, Chad A. Galloway, Sonal Dalvi, Anthony A. Emanuel, Jared A. Mereness, Whitney Black, Lauren Winschel, Celia Soto, Yiming Li, Yuanhui Song, William DeMaria, Akhilesh Kumar, Igor Slukvin, Michael P. Schwartz, William L. Murphy, Bela Anand-Apte, Mina Chung, Danielle S. W. Benoit, Ruchira Singh
Summary: Researchers have developed a 3D RPE-CC model that mimics key features of healthy and AMD/MD eyes while providing modular control over RPE and CC layers. They have found that both RPE and mesenchyme-secreted factors are necessary for the formation of fenestrated CC-like vasculature, and that CC atrophy and/or CNV can be initiated by patient serum or mutant RPE-secreted factors. Additionally, FGF2 and matrix metalloproteinases have been identified as potential therapeutic targets for AMD/MDs.
Correction
Cell & Tissue Engineering
Kannan V. Manian, Chad A. Galloway, Sonal Dalvi, Anthony A. Emanuel, Jared A. Mereness, Whitney Black, Lauren Winschel, Celia Soto, Yiming Li, Yuanhui Song, William DeMaria, Akhilesh Kumar, Igor Slukvin, Michael P. Schwartz, William L. Murphy, Bela Anand-Apte, Mina Chung, Danielle S. W. Benoit, Ruchira Singh
Article
Cell & Tissue Engineering
Saritha S. D'Souza, Akhilesh Kumar, Jason Weinfurter, Mi Ae Park, John Maufort, Lihong Tao, HyunJun Kang, Samuel T. Dettle, Thaddeus Golos, James A. Thomson, Matthew R. Reynolds, Igor Slukvin
Summary: This study successfully targeted the CCR5 locus using CRISPR-Cas9 technology, resulting in HIV-resistant human T cells. The edited cells did not affect hematopoietic and T cell differentiation, and were unable to support replication of CCR5-tropic simian immunodeficiency viruses. This provides a platform for further exploration of AIDS therapies using gene-edited iPSCs in a nonhuman primate model.
Article
Biotechnology & Applied Microbiology
Rachel Rui Xia Lim, Mi Ae Park, Long Hui Wong, Sumanto Haldar, Kevin Junliang Lim, Niranjan Nagarajan, Christiani Jeyakumar Henry, Yuan Rong Jiang, Oleg Vladimirovich Moskvin
Summary: This study found that the beneficial effects of dietary intervention on blood lipid profile are associated with an upregulation of the Clostridia class in the gut microbiota. During the dietary intervention, the relative abundance of a single species - Clostridium genus - significantly increased, and oils with high concentration of omega-3 PUFA showed faster and more robust responses in the intestinal microbiota.
NPJ BIOFILMS AND MICROBIOMES
(2022)
Article
Hematology
Saritha S. D'Souza, Akhilesh Kumar, John Maufort, Jason T. Weinfurter, Matthew Raymond, Nick S. Strelchenko, Elizabeth Perrin, Jennifer Coonen, Andres Mejia, Heather A. Simmons, Bruce E. Torbett, Matthew Reynolds, James A. Thomson, Igor I. Slukvin
Summary: The administration of ex vivo expanded somatic myeloid progenitors is explored as a way to accelerate myeloid recovery. Recent studies have shown the potential of hematopoietic progenitors derived from MHC homozygous iPSCs in treating cytopenia with good tolerance and safety in experimental animals.
Article
Multidisciplinary Sciences
Jason T. Weinfurter, Saritha S. D'Souza, Lea M. Matschke, Sarah Bennett, Laurel E. Kelnhofer-Millevolte, Kran Suknuntha, Akhilesh Kumar, Jennifer Coonen, Christian M. Capitini, Peiman Hematti, Thaddeus G. Golos, Igor I. Slukvin, Matthew R. Reynolds
Summary: Allogeneic hematopoietic stem cell transplants can reduce HIV reservoirs, but the mechanism is not fully understood.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Frank Cichocki, Ryan Bjordahl, Jodie P. Goodridge, Sajid Mahmood, Svetlana Gaidarova, Ramzey Abujarour, Zachary B. Davis, Aimee Merino, Katie Tuininga, Hongbo Wang, Akhilesh Kumar, Brian Groff, Alec Witty, Greg Bonello, Janel Huffman, Thomas Dailey, Tom T. Lee, Karl-Johan Malmberg, Bruce Walcheck, Uta Hoepken, Armin Rehm, Bahram Valamehr, Jeffrey S. Miller
Summary: The study presents quadruple gene-engineered induced pluripotent stem cell (iPSC)-derived NK cells as a potential therapy for multiple myeloma, demonstrating durable antitumor activity independent of exogenous cytokine support.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Seung Han Son, Min Young Kim, Young Su Lim, Hyeon Cheol Jin, June Ho Shin, Jae Kyu Yi, Sungwoo Choi, Mi Ae Park, Ji Hyung Chae, Ho Chul Kang, Young Jin Lee, Vladimir N. Uversky, Chul Geun Kim
Summary: This study uncovers a novel mechanism of CP2c degradation through SUMO1/PSME3/20S proteasome pathway and its significance in cell cycle progression.
Article
Chemistry, Multidisciplinary
Seung Han Son, Min Young Kim, Sungwoo Choi, Ji Sook Kim, Yong Sang Lee, Sangwon Lee, Yeon Ju Lee, Jin Youn Lee, Seol Eui Lee, Young Su Lim, Dae Hyun Ha, Eonju Oh, Young-Bin Won, Chang-Jun Ji, Mi Ae Park, Boram Kim, Kyu Tae Byun, Min Sung Chung, Jaemin Jeong, Dongho Choi, Eun Jung Baek, Eung-Ho Cho, Sang-Bum Kim, A. Reum Je, Hee-Seok Kweon, Hyun Sook Park, Dongsun Park, June Sung Bae, Se Jin Jang, Chae-Ok Yun, Ji Hyung Chae, Jin-Won Lee, Su-Jae Lee, Chan Gil Kim, Ho Chul Kang, Vladimir N. Uversky, Chul Geun Kim
Summary: This study presents a cell-penetrable peptide, ACP52C, that induces apoptosis in cancer cells through transcription activity-independent mechanisms. It dissociates transcription factor CP2c complexes and inhibits TDP2, leading to cancer-specific apoptosis. The study also finds that ACP52C can be sensitized by CASP2 inhibition and derivatives of ACP52C show improved pharmacokinetics and reduced cancer burden.
Article
Multidisciplinary Sciences
Jenna Kropp Schmidt, Nick Strelchenko, Mi Ae Park, Yun Hee Kim, Katherine D. Mean, Michele L. Schotzko, Hyun Jun Kang, Thaddeus G. Golos, Igor I. Slukvin
SCIENTIFIC REPORTS
(2020)
Article
Biology
Akhilesh Kumar, Saritha S. D'Souza, Gene Uenishi, Mi Ae Park, Jeong Hee Lee, Igor I. Slukvin
