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https://www.readbyqxmd.com/read/28869683/runx1c-regulates-hematopoietic-differentiation-of-human-pluripotent-stem-cells-possibly-in-cooperation-with-proinflammatory-signaling
#1
Oscar Navarro-Montero, Veronica Ayllon, Mar Lamolda, Lourdes López-Onieva, Rosa Montes, Clara Bueno, Elizabeth Ng, Xiomara Guerrero-Carreno, Tamara Romero, Damià Romero-Moya, Ed Stanley, Andrew Elefanty, Verónica Ramos-Mejia, Pablo Menendez, Pedro J Real
Runt-related transcription factor 1 (Runx1) is a master hematopoietic transcription factor essential for hematopoietic stem cell (HSC) emergence. Runx1-deficient mice die during early embryogenesis due to the inability to establish definitive hematopoiesis. Here, we have used human pluripotent stem cells (hPSCs) as model to study the role of RUNX1 in human embryonic hematopoiesis. Although the three RUNX1 isoforms a, b, and c were induced in CD45+ hematopoietic cells, RUNX1c was the only isoform induced in hematoendothelial progenitors (HEPs)/hemogenic endothelium...
September 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28820341/cell-cycle-dynamics-and-complement-expression-distinguishes-mature-haematopoietic-subsets-arising-from-hemogenic-endothelium
#2
Joan P Zape, Carlos O Lizama, Kelly M Cautivo, Ann C Zovein
The emergence of haematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelium results in the formation of sizeable HSPC clusters attached to the vascular wall. We evaluate the cell cycle and proliferation of HSPCs involved in cluster formation, as well as the molecular signatures from their initial appearance to the point when cluster cells are capable of adult engraftment (definitive HSCs). We uncover a non-clonal origin of HSPC clusters with differing cell cycle, migration, and cell signaling attributes...
October 2, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28803914/targeted-disruption-of-tcf12-reveals-heb-as-essential-in-human-mesodermal-specification-and-hematopoiesis
#3
Yang Li, Patrick M Brauer, Jastaranpreet Singh, Sintia Xhiku, Kogulan Yoganathan, Juan Carlos Zúñiga-Pflücker, Michele K Anderson
Hematopoietic stem cells arise from mesoderm-derived hemogenic endothelium (HE) during embryogenesis in a process termed endothelial-hematopoietic transition (EHT). To better understand the gene networks that control this process, we investigated the role of the transcription factor HEB (TCF12) by disrupting the TCF12 gene locus in human embryonic stem cells (hESCs) and inducing them to differentiate toward hematopoietic outcomes. HEB-deficient hESCs retained key features of pluripotency, including expression of SOX2 and SSEA-4 and teratoma formation, while NANOG expression was reduced...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28757166/p53-mediates-failure-of-human-definitive-hematopoiesis-in-dyskeratosis-congenita
#4
Wilson Chun Fok, Evandro Luis de Oliveira Niero, Carissa Dege, Kirsten Ann Brenner, Christopher Michael Sturgeon, Luis Francisco Zirnberger Batista
Dyskeratosis congenita (DC) is a bone marrow failure syndrome associated with telomere dysfunction. The progression and molecular determinants of hematopoietic failure in DC remain poorly understood. Here, we use the directed differentiation of human embryonic stem cells harboring clinically relevant mutations in telomerase to understand the consequences of DC-associated mutations on the primitive and definitive hematopoietic programs. Interestingly, telomere shortening does not broadly impair hematopoiesis, as primitive hematopoiesis is not impaired in DC cells...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28641611/-dmso-promotes-hematopoietic-differentiation-of-human-embryonic-stem-cells-in-vitro
#5
Hong-Tao Wang, Meng-Ge Wang, Xin Liu, Pei Su, Lei-Sheng Zhang, Cui-Cui Liu, Yu Wang, Dan Wu, Qian Tu, Jia-Xi Zhou
OBJECTIVE: To explore the role of dimethyl sulfoxide (DMSO) in the hematopoietic differentiation of human embryonic stem cells (hESCs). METHODS: The role of DMSO in hematopoietic differentiation of hESC was investigated by using a established stepwise hematopoietic differentiation system from hESC, immunofluorescouse assay and flow cytometry. Furthermore, the window phase of DMSO action was explored by adding it to the different stage of hematopoietic differentiation...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28621430/disruption-of-the-aortic-wall-by-coelomic-lining-derived-mesenchymal-cells-accompanies-the-onset-of-aortic-hematopoiesis
#6
Alaa A Arraf, Marella F T R De Bruijn, Thomas M Schultheiss
In vertebrates, definitive hematopoietic stem cells (HSCs) first emerge in the ventral wall of the aorta in the Aorta-Gonad-Mesonephros (AGM) region of the embryo, where they differentiate from a specialized type of endothelium termed Hemogenic Endothelium (HE). While the transition from HE to hematopoietic tissue has received much experimental attention, much less is known regarding generation of HE itself. The current study investigates the emergence of the HE in the chick embryo aorta. Using the HE marker Runx1 as well as a new chicken-reactive antibody to the endothelial marker VE-Cadherin, we document the relationship between the emerging HE and surrounding tissues, particularly the coelomic epithelium (CE) and CE-derived sub-aortic mesenchyme...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28594660/regulation-of-the-hematopoietic-stem-cell-lifecycle-by-the-endothelial-niche
#7
REVIEW
Pradeep Ramalingam, Michael G Poulos, Jason M Butler
PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a vast repertoire of biological processes crucial for HSC maintenance throughout its lifespan. In this review, we will discuss recent findings in endothelial niche-mediated regulation of HSC function during development, aging and regenerative conditions...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28584091/dissecting-bmp-signaling-input-into-the-gene-regulatory-networks-driving-specification-of-the-blood-stem-cell-lineage
#8
Arif Kirmizitas, Stuart Meiklejohn, Aldo Ciau-Uitz, Rachel Stephenson, Roger Patient
Hematopoietic stem cells (HSCs) that sustain lifelong blood production are created during embryogenesis. They emerge from a specialized endothelial population, termed hemogenic endothelium (HE), located in the ventral wall of the dorsal aorta (DA). In Xenopus, we have been studying the gene regulatory networks (GRNs) required for the formation of HSCs, and critically found that the hemogenic potential is defined at an earlier time point when precursors to the DA express hematopoietic as well as endothelial genes, in the definitive hemangioblasts (DHs)...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28502982/why-are-hematopoietic-stem-cells-so-sexy-on-a-search-for-developmental-explanation
#9
REVIEW
M Z Ratajczak
Evidence has accumulated that normal human and murine hematopoietic stem cells express several functional pituitary and gonadal sex hormones, and that, in fact, some sex hormones, such as androgens, have been employed for many years to stimulate hematopoiesis in patients with bone marrow aplasia. Interestingly, sex hormone receptors are also expressed by leukemic cell lines and blasts. In this review, I will discuss the emerging question of why hematopoietic cells express these receptors. A tempting hypothetical explanation for this phenomenon is that hematopoietic stem cells are related to subpopulation of migrating primordial germ cells...
August 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28450163/murine-hemogenic-endothelial-precursors-display-heterogeneous-hematopoietic-potential-ex%C3%A2-vivo
#10
Miguel Ganuza, Brandon Hadland, Ashley Chabot, Chen Li, Guolian Kang, Irwin Bernstein, Shannon McKinney-Freeman
Hematopoietic stem and progenitor cells (HSPCs) sustain life-long hematopoiesis and are first detected in the embryo by transplantation at embryonic day 10.5 (E10.5). HSPCs are mesodermal in origin and ultimately emerge from a subset of arterial endothelium (i.e., hemogenic endothelium [HE]), which is highly concentrated in the aorta-gonad-mesonephros region of the midgestation embryo. Here, we used clonal ex vivo assays, in which endothelial cells isolated from the midgestation aorta and vitelline and umbilical arteries are co-cultured on supportive stroma, to show that only about 0...
July 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28416284/distinct-roles-for-matrix-metalloproteinases-2-and-9-in-embryonic-hematopoietic-stem-cell-emergence-migration-and-niche-colonization
#11
Lindsay N Theodore, Elliott J Hagedorn, Mauricio Cortes, Kelsey Natsuhara, Sarah Y Liu, Julie R Perlin, Song Yang, Madeleine L Daily, Leonard I Zon, Trista E North
Hematopoietic stem/progenitor cells (HSPCs) are formed during ontogeny from hemogenic endothelium in the ventral wall of the dorsal aorta (VDA). Critically, the cellular mechanism(s) allowing HSPC egress and migration to secondary niches are incompletely understood. Matrix metalloproteinases (MMPs) are inflammation-responsive proteins that regulate extracellular matrix (ECM) remodeling, cellular interactions, and signaling. Here, inhibition of vascular-associated Mmp2 function caused accumulation of fibronectin-rich ECM, retention of runx1/cmyb(+) HSPCs in the VDA, and delayed caudal hematopoietic tissue (CHT) colonization; these defects were absent in fibronectin mutants, indicating that Mmp2 facilitates endothelial-to-hematopoietic transition via ECM remodeling...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28338096/identification-of-cardiac-hemo-vascular-precursors-and-their-requirement-of-sphingosine-1-phosphate-receptor-1-for-heart-development
#12
Yan Hu, Brian C Belyea, Minghong Li, Joachim R Göthert, R Ariel Gomez, Maria Luisa S Sequeira-Lopez
The cardiac endothelium plays a crucial role in the development of a functional heart. However, the precise identification of the endocardial precursors and the mechanisms they require for their role in heart morphogenesis are not well understood. Using in vivo and in vitro cell fate tracing concomitant with specific cell ablation and embryonic heart transplantation studies, we identified a unique set of precursors which possess hemogenic functions and express the stem cell leukemia (SCL) gene driven by its 5' enhancer...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302184/cytokine-free-directed-differentiation-of-human-pluripotent-stem-cells-efficiently-produces-hemogenic-endothelium-with-lymphoid-potential
#13
Yekaterina Galat, Svetlana Dambaeva, Irina Elcheva, Aaruni Khanolkar, Kenneth Beaman, Philip M Iannaccone, Vasiliy Galat
BACKGROUND: The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification...
March 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28299650/the-role-of-runx1-in-embryonic-blood-cell-formation
#14
REVIEW
Amanda D Yzaguirre, Marella F T R de Bruijn, Nancy A Speck
The de novo generation of hematopoietic stem and progenitor cells (HSPC) occurs solely during embryogenesis from a population of epithelial cells called hemogenic endothelium (HE). During midgestation HE cells in multiple intra- and extraembryonic vascular beds leave the vessel wall as they transition into HSPCs in a process termed the endothelial to hematopoietic transition (EHT). Runx1 expression in HE cells orchestrates the transcriptional switch necessary for the transdifferentiation of endothelial cells into functional HSPCs...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28271994/nkx2-5-marks-angioblasts-that-contribute-to-hemogenic-endothelium-of-the-endocardium-and-dorsal-aorta
#15
Lyad Zamir, Reena Singh, Elisha Nathan, Ralph Patrick, Oren Yifa, Yfat Yahalom-Ronen, Alaa A Arraf, Thomas M Schultheiss, Shengbao Suo, Jing-Dong Jackie Han, Guangdun Peng, Naihe Jing, Yuliang Wang, Nathan Palpant, Patrick Pl Tam, Richard P Harvey, Eldad Tzahor
Novel regenerative therapies may stem from deeper understanding of the mechanisms governing cardiovascular lineage diversification. Using enhancer mapping and live imaging in avian embryos, and genetic lineage tracing in mice, we investigated the spatio-temporal dynamics of cardiovascular progenitor populations. We show that expression of the cardiac transcription factor Nkx2.5 marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts...
March 8, 2017: ELife
https://www.readbyqxmd.com/read/28090699/modelling-irf8-deficient-human-hematopoiesis-and-dendritic-cell-development-with-engineered-ips-cells
#16
Stephanie Sontag, Malrun Förster, Jie Qin, Paul Wanek, Saskia Mitzka, Herdit M Schüler, Steffen Koschmieder, Stefan Rose-John, Kristin Seré, Martin Zenke
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28087636/r-spondin-1-is-required-for-specification-of-hematopoietic-stem-cells-through-wnt16-and-vegfa-signaling-pathways
#17
Jamie R Genthe, Wilson K Clements
Hematopoietic stem cells (HSCs) are the therapeutic component of bone marrow transplants, but finding immune-compatible donors limits treatment availability and efficacy. Recapitulation of endogenous specification during development is a promising approach to directing HSC specification in vitro, but current protocols are not capable of generating authentic HSCs with high efficiency. Across phyla, HSCs arise from hemogenic endothelium in the ventral floor of the dorsal aorta concurrent with arteriovenous specification and intersegmental vessel (ISV) sprouting, processes regulated by Notch and Wnt...
February 15, 2017: Development
https://www.readbyqxmd.com/read/28043822/hemangioblast-hemogenic-endothelium-and-primitive-versus-definitive-hematopoiesis
#18
REVIEW
Georges Lacaud, Valerie Kouskoff
The types of progenitors generated during the successive stages of embryonic blood development are now fairly well characterized. The terminology used to describe these waves, however, can still be confusing. What is truly primitive? What is uniquely definitive? These questions become even more challenging to answer when blood progenitors are derived in vitro upon the differentiation of embryonic stem cells or induced pluripotent stem cells. Similarly, the cellular origin of these blood progenitors can be controversial...
May 2017: Experimental Hematology
https://www.readbyqxmd.com/read/27880904/lyve1-marks-the-divergence-of-yolk-sac-definitive-hemogenic-endothelium-from-the-primitive-erythroid-lineage
#19
Lydia K Lee, Yasamine Ghorbanian, Wenyuan Wang, Yanling Wang, Yeon Joo Kim, Irving L Weissman, Matthew A Inlay, Hanna K A Mikkola
The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27861498/somite-derived-retinoic-acid-regulates-zebrafish-hematopoietic-stem-cell-formation
#20
Laura M Pillay, Kacey J Mackowetzky, Sonya A Widen, Andrew Jan Waskiewicz
Hematopoietic stem cells (HSCs) are multipotent progenitors that generate all vertebrate adult blood lineages. Recent analyses have highlighted the importance of somite-derived signaling factors in regulating HSC specification and emergence from dorsal aorta hemogenic endothelium. However, these factors remain largely uncharacterized. We provide evidence that the vitamin A derivative retinoic acid (RA) functions as an essential regulator of zebrafish HSC formation. Temporal analyses indicate that RA is required for HSC gene expression prior to dorsal aorta formation, at a time when the predominant RA synthesis enzyme, aldh1a2, is strongly expressed within the paraxial mesoderm and somites...
2016: PloS One
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