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JOURNAL ARTICLE
Jonas L Fowler, Sherry Li Zheng, Alana Nguyen, Angela Chen, Xiaochen Xiong, Timothy Chai, Julie Y Chen, Daiki Karigane, Allison M Banuelos, Kouta Niizuma, Kensuke Kayamori, Toshinobu Nishimura, M Kyle Cromer, David Gonzalez-Perez, Charlotte Mason, Daniel Dan Liu, Leyla Yilmaz, Lucile Miquerol, Matthew H Porteus, Vincent C Luca, Ravindra Majeti, Hiromitsu Nakauchi, Kristy Red-Horse, Irving L Weissman, Lay Teng Ang, Kyle M Loh
The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (∼E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo. Guided by the arterial origins of blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic progenitors within 10 days...
April 1, 2024: Developmental Cell
#2
JOURNAL ARTICLE
Zhaohua Cai, Shaojin You, Zhixue Liu, Ping Song, Fujie Zhao, Junqing An, Ye Ding, Ben He, Ming-Hui Zou
During the maturation of hematopoietic stem/progenitor cells (HSPCs) to fully differentiated mature B lymphocytes, developing lymphocytes may undergo malignant transformation and produce B-cell lymphomas. Emerging evidence shows that through the endothelial-hematopoietic transition, specialized endothelial cells called the hemogenic endothelium can differentiate into HSPCs. However, the contribution of genetic defects in hemogenic endothelial cells to B-cell lymphomagenesis has not yet been investigated. Here, we report that mice with endothelial cell-specific deletion of Fbw7 spontaneously developed diffuse large B-cell lymphoma (DLBCL) following Bcl6 accumulation...
March 14, 2024: Cell Death & Disease
#3
JOURNAL ARTICLE
Roshana Thambyrajah, Maria Maqueda, Wen Hao Neo, Kathleen Imbach, Yolanda Guillén, Daniela Grases, Zaki Fadlullah, Stefano Gambera, Francesca Matteini, Xiaonan Wang, Fernando J Calero-Nieto, Manel Esteller, Maria Carolina Florian, Eduard Porta, Rui Benedito, Berthold Göttgens, Georges Lacaud, Lluis Espinosa, Anna Bigas
Hematopoietic stem cells (HSCs) develop from the hemogenic endothelium (HE) in the aorta- gonads-and mesonephros (AGM) region and reside within Intra-aortic hematopoietic clusters (IAHC) along with hematopoietic progenitors (HPC). The signalling mechanisms that distinguish HSCs from HPCs are unknown. Notch signaling is essential for arterial specification, IAHC formation and HSC activity, but current studies on how Notch segregates these different fates are inconsistent. We now demonstrate that Notch activity is highest in a subset of, GFI1 + , HSC-primed HE cells, and is gradually lost with HSC maturation...
February 21, 2024: Nature Communications
#4
JOURNAL ARTICLE
Xiaoyi Cheng, Radwa Barakat, Giulia Pavani, Masuma Khatun Usha, Rodolfo Calderon, Elizabeth Snella, Abigail Gorden, Yudi Zhang, Paul Gadue, Deborah L French, Karin S Dorman, Antonella Fidanza, Clyde A Campbell, Raquel Espin-Palazon
Uncovering the mechanisms regulating hematopoietic specification not only would overcome current limitations related to hematopoietic stem and progenitor cell (HSPC) transplantation, but also advance cellular immunotherapies. However, generating functional human induced pluripotent stem cell (hiPSC)-derived HSPCs and their derivatives has been elusive, necessitating a better understanding of the developmental mechanisms that trigger HSPC specification. Here, we reveal that early activation of the Nod1-Ripk2-NF-kB inflammatory pathway in endothelial cells (ECs) primes them to switch fate towards definitive hemogenic endothelium, a pre-requisite to specify HSPCs...
November 23, 2023: Nature Communications
#5
JOURNAL ARTICLE
Jorge O Múnera, Daniel O Kechele, Carine Bouffi, Na Qu, Ran Jing, Pritiprasanna Maity, Jacob R Enriquez, Lu Han, Ian Campbell, Maxime M Mahe, Heather A McCauley, Xinghao Zhang, Nambirajan Sundaram, Jonathan R Hudson, Adrian Zarsozo-Lacoste, Suman Pradhan, Kentaro Tominaga, J Guillermo Sanchez, Alison A Weiss, Praneet Chatuvedi, Jason R Spence, Mariam Hachimi, Trista North, George Q Daley, Christopher N Mayhew, Yueh-Chiang Hu, Takanori Takebe, Michael A Helmrath, James M Wells
Most organs have tissue-resident immune cells. Human organoids lack these immune cells, which limits their utility in modeling many normal and disease processes. Here, we describe that pluripotent stem cell-derived human colonic organoids (HCOs) co-develop a diverse population of immune cells, including hemogenic endothelium (HE)-like cells and erythromyeloid progenitors that undergo stereotypical steps in differentiation, resulting in the generation of functional macrophages. HCO macrophages acquired a transcriptional signature resembling human fetal small and large intestine tissue-resident macrophages...
November 2, 2023: Cell Stem Cell
#6
JOURNAL ARTICLE
Yohko Kitagawa, Akihiro Ikenaka, Ryohichi Sugimura, Akira Niwa, Megumu K Saito
Cell differentiation is achieved by acquiring a cell type-specific transcriptional program and epigenetic landscape. While the cell type-specific patterning of enhancers has been shown to precede cell fate decisions, it remains unclear how regulators of these enhancers are induced to initiate cell specification and how they appropriately restrict cells that differentiate. Here, using embryonic stem cell-derived hematopoietic cell differentiation cultures, we show the activation of some hematopoietic enhancers during arterialization of hemogenic endothelium, a prerequisite for hematopoiesis...
October 20, 2023: IScience
#7
JOURNAL ARTICLE
Pankaj Sahai-Hernandez, Claire Pouget, Shai Eyal, Ondrej Svoboda, Jose Chacon, Lin Grimm, Tor Gjøen, David Traver
Development of the dorsal aorta is a key step in the establishment of the adult blood-forming system, since hematopoietic stem and progenitor cells (HSPCs) arise from ventral aortic endothelium in all vertebrate animals studied. Work in zebrafish has demonstrated that arterial and venous endothelial precursors arise from distinct subsets of lateral plate mesoderm. Here, we profile the transcriptome of the earliest detectable endothelial cells (ECs) during zebrafish embryogenesis to demonstrate that tissue-specific EC programs initiate much earlier than previously appreciated, by the end of gastrulation...
September 11, 2023: ELife
#8
JOURNAL ARTICLE
Sara Menegatti, Bethany Potts, Roberto Paredes, Eva Garcia-Alegria, Syed Murtuza Baker, Valerie Kouskoff
During embryonic development, all blood progenitors are initially generated from endothelial cells that acquire a hemogenic potential. Blood progenitors emerge through an endothelial-to-hematopoietic transition regulated by the transcription factor RUNX1. To date, we still know very little about the molecular characteristics of hemogenic endothelium and the molecular changes underlying the transition from endothelium to hematopoiesis. Here, we analyzed at the single cell level a human embryonic stem cell-derived endothelial population containing hemogenic potential...
September 15, 2023: IScience
#9
JOURNAL ARTICLE
Soo-Been Jeon, Hyebin Koh, A-Reum Han, Jieun Kim, Sunghun Lee, Jae-Ho Lee, Seung-Soon Im, Young-Sup Yoon, Jong-Hee Lee, Ji Yoon Lee
Red blood cell (RBC) generation from human pluripotent stem cells (PSCs) offers potential for innovative cell therapy in regenerative medicine as well as developmental studies. Ex vivo erythropoiesis from PSCs is currently limited by the low efficiency of functional RBCs with β-globin expression in culture systems. During induction of β-globin expression, the absence of a physiological microenvironment, such as a bone marrow niche, may impair cell maturation and lineage specification. Here, we describe a simple and reproducible culture system that can be used to generate erythroblasts with β-globin expression...
August 25, 2023: NPJ Regenerative Medicine
#10
JOURNAL ARTICLE
Issac Goh, Rachel A Botting, Antony Rose, Simone Webb, Justin Engelbert, Yorick Gitton, Emily Stephenson, Mariana Quiroga Londoño, Michael Mather, Nicole Mende, Ivan Imaz-Rosshandler, Lu Yang, Dave Horsfall, Daniela Basurto-Lozada, Nana-Jane Chipampe, Victoria Rook, Jimmy Tsz Hang Lee, Mai-Linh Ton, Daniel Keitley, Pavel Mazin, M S Vijayabaskar, Rebecca Hannah, Laure Gambardella, Kile Green, Stephane Ballereau, Megumi Inoue, Elizabeth Tuck, Valentina Lorenzi, Kwasi Kwakwa, Clara Alsinet, Bayanne Olabi, Mohi Miah, Chloe Admane, Dorin-Mirel Popescu, Meghan Acres, David Dixon, Thomas Ness, Rowen Coulthard, Steven Lisgo, Deborah J Henderson, Emma Dann, Chenqu Suo, Sarah J Kinston, Jong-Eun Park, Krzysztof Polanski, John Marioni, Stijn van Dongen, Kerstin B Meyer, Marella de Bruijn, James Palis, Sam Behjati, Elisa Laurenti, Nicola K Wilson, Roser Vento-Tormo, Alain Chédotal, Omer Bayraktar, Irene Roberts, Laura Jardine, Berthold Göttgens, Sarah A Teichmann, Muzlifah Haniffa
The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation. We reconstructed the emergence and decline of YS hematopoietic stem and progenitor cells from hemogenic endothelium and revealed a YS-specific accelerated route to macrophage production that seeds developing organs...
August 18, 2023: Science
#11
JOURNAL ARTICLE
Cross-species transcriptomics reveals bifurcation point during the arterial-to-hemogenic transition.
Shaokang Mo, Kengyuan Qu, Junfeng Huang, Qiwei Li, Wenqing Zhang, Kuangyu Yen
Hemogenic endothelium (HE) with hematopoietic stem cell (HSC)-forming potential emerge from specialized arterial endothelial cells (AECs) undergoing the endothelial-to-hematopoietic transition (EHT) in the aorta-gonad-mesonephros (AGM) region. Characterization of this AECs subpopulation and whether this phenomenon is conserved across species remains unclear. Here we introduce HomologySeeker, a cross-species method that leverages refined mouse information to explore under-studied human EHT. Utilizing single-cell transcriptomic ensembles of EHT, HomologySeeker reveals a parallel developmental relationship between these two species, with minimal pre-HSC signals observed in human cells...
August 9, 2023: Communications Biology
#12
JOURNAL ARTICLE
Pietro Cacialli, Serkan Dogan, Tanja Linnerz, Corentin Pasche, Julien Y Bertrand
Hematopoietic stem cells (HSCs) guarantee the continuous supply of all blood lineages during life. In response to stress, HSCs are capable of extensive proliferative expansion, whereas in steady state, HSCs largely remain in a quiescent state to prevent their exhaustion. DNA replication is a very complex process, where many factors need to exert their functions in a perfectly concerted manner. Mini-chromosome-maintenance protein 10 (Mcm10) is an important replication factor, required for proper assembly of the eukaryotic replication fork...
July 11, 2023: Stem Cell Reports
#13
JOURNAL ARTICLE
Thierry Jaffredo
This article summarizes Françoise Dieterlen's major scientific discoveries about the hematopoietic and endothelial systems during her 40 years' career. Her most remarkable achievements include notably the demonstration of an intraembryonic source of hematopoietic stem cells, the characterization of the polarization of the aorta, the identification of a hemogenic endothelium as well as that of the allantois as an organ of hematopoietic amplification in the mouse embryo, and the demonstration of the existence of a hemogenic endothelium capable of generating hematopoietic stem cells in the bone marrow of the chicken and mouse embryo...
2023: Biologie Aujourd'hui
#14
JOURNAL ARTICLE
Kuo Liu, Hengwei Jin, Shaohua Zhang, Muxue Tang, Xinfeng Meng, Yan Li, Wenjuan Pu, Kathy O Lui, Bin Zhou
Cardiac resident macrophages play vital roles in heart development, homeostasis, repair, and regeneration. Recent studies documented the hematopoietic potential of cardiac endothelium that supports the generation of cardiac macrophages and peripheral blood cells in mice. However, the conclusion was not strongly supported by previous genetic tracing studies, given the non-specific nature of conventional Cre-loxP tracing tools. Here, we develop an intercellular genetic labeling system that can permanently trace heart-specific endothelial cells based on cell-cell interaction in mice...
June 15, 2023: Developmental Cell
#15
JOURNAL ARTICLE
Yuki Sato, Mugiho Shigematsu, Maria Shibata-Kanno, Sho Maejima, Chie Tamura, Hirotaka Sakamoto
Endothelial-to-hematopoietic transition (EHT) is crucial for hematopoietic stem cell (HSC) generation. During EHT, the morphology of hemogenic endothelial cells (HECs) changes from flat and adherent to spherical hematopoietic cells, which detach from the dorsal aorta. HECs attain a rounded shape in a mitosis-independent manner before cell adhesion termination, suggesting an atypical cell-rounding mechanism. However, the direct mechanisms underlying this change in cell morphology during EHT remain unclear. Here, we show that large vacuoles were transiently formed in avian HECs, and that aquaporin 1 (AQP1) was localized in the vacuole and plasma membranes...
June 1, 2023: Development
#16
JOURNAL ARTICLE
Ho Sun Jung, Kran Suknuntha, Yun Hee Kim, Peng Liu, Samuel T Dettle, Divine Mensah Sedzro, Portia R Smith, James A Thomson, Irene M Ong, Igor I Slukvin
Hemogenic endothelium (HE) is the main source of blood cells in the embryo. To improve blood manufacturing from human pluripotent stem cells (hPSCs), it is essential to define the molecular determinants that enhance HE specification and promote development of the desired blood lineage from HE. Here, using SOX18-inducible hPSCs, we revealed that SOX18 forced expression at the mesodermal stage, in contrast to its homolog SOX17, has minimal effects on arterial specification of HE, expression of HOXA genes and lymphoid differentiation...
May 19, 2023: IScience
#17
JOURNAL ARTICLE
Yongqin Li, Jianyi Ding, Daisuke Araki, Jizhong Zou, Andre Larochelle
Several differentiation protocols enable the emergence of hematopoietic stem and progenitor cells (HSPCs) from human induced pluripotent stem cells (iPSCs), yet optimized schemes to promote the development of HSPCs with self-renewal, multilineage differentiation and engraftment potential are lacking. To improve human iPSC differentiation methods, we modulated WNT, Activin/Nodal and MAPK signaling pathways by stage-specific addition of small molecule regulators CHIR99021, SB431542 and LY294002, respectively, and measured the impact on hematoendothelial formation in culture...
May 23, 2023: Stem Cells
#18
JOURNAL ARTICLE
Evelynn Vergauwen, Ramses Forsyth, Alexander Vortmeyer, Sven Gläsker
Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome that targets a highly selective subset of organs causing specific types of tumors. The biological basis for this principle of organ selectivity and tumor specificity is not well understood. VHL-associated hemangioblastomas share similar molecular and morphological features with embryonic blood and vascular precursor cells. Therefore, we suggest that VHL hemangioblastomas are derived from developmentally arrested hemangioblastic lineage keeping their potential of further differentiation...
April 29, 2023: Cancers
#19
JOURNAL ARTICLE
Honghu Li, Qian Luo, Shuyang Cai, Ruxiu Tie, Ye Meng, Wei Shan, Yulin Xu, Xiangjun Zeng, Pengxu Qian, He Huang
BACKGROUND: In vertebrates, hematopoietic stem and progenitor cells (HSPCs) emerge from hemogenic endothelium in the floor of the dorsal aorta and subsequently migrate to secondary niches where they expand and differentiate into committed lineages. Glia maturation factor γ (gmfg) is a key regulator of actin dynamics that was shown to be highly expressed in hematopoietic tissue. Our goal is to investigate the role and mechanism of gmfg in embryonic HSPC development. METHODS: In-depth bioinformatics analysis of our published RNA-seq data identified gmfg as a cogent candidate gene implicated in HSPC development...
April 30, 2023: Stem Cell Research & Therapy
#20
JOURNAL ARTICLE
Linh T Trinh, Anna B Osipovich, Bryan Liu, Shristi Shrestha, Jean-Philippe Cartailler, Christopher V E Wright, Mark A Magnuson
During early embryogenesis, the transcription factor SOX17 contributes to hepato-pancreato-biliary system formation and vascular-hematopoietic emergence. To better understand Sox17 function in the developing endoderm and endothelium, we developed a dual-color temporal lineage-tracing strategy in mice combined with single-cell RNA sequencing to analyze 6,934 cells from Sox17-expressing lineages at embryonic day 9.0-9.5. Our analyses showed 19 distinct cellular clusters combined from all three germ layers. Differential gene expression, trajectory and RNA-velocity analyses of endothelial cells revealed a heterogenous population of uncommitted and specialized endothelial subtypes, including two hemogenic populations that arise from different origins...
April 21, 2023: Stem Cells
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