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https://www.readbyqxmd.com/read/29622030/mapping-human-pluripotent-stem-cell-differentiation-pathways-using-high-throughput-single-cell-rna-sequencing
#1
Xiaoping Han, Haide Chen, Daosheng Huang, Huidong Chen, Lijiang Fei, Chen Cheng, He Huang, Guo-Cheng Yuan, Guoji Guo
BACKGROUND: Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell level differentiation roadmap for hPSCs has not been achieved. RESULTS: We use high throughput single-cell RNA-sequencing (scRNA-seq), based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body system. We present a cellular-state landscape for hPSC early differentiation that covers multiple cellular lineages, including neural, muscle, endothelial, stromal, liver, and epithelial cells...
April 5, 2018: Genome Biology
https://www.readbyqxmd.com/read/29616721/early-hematopoietic-and-vascular-development-in-the-chick
#2
Hiroki Nagai, Masahiro Shin, Wei Weng, Fumie Nakazawa, Lars Martin Jakt, Cantas Alev, Guojun Sheng
The field of hematopoietic and vascular developmental research owes its origin to the chick embryo. Many key concepts, such as the hematopoietic stem cell, hemangioblast and hemogenic endothelium, were first proposed in this model organism. Genetically tractable models have gradually replaced the chick in the past two decades. However, advances in comparative genomics, transcriptomics and promoteromics promise a re-emergence of the chick embryo as a powerful model for hematopoietic/vascular research. This review summarizes the current status of our understanding of early blood/vascular development in the chick, focusing primarily on the processes of primitive hematopoiesis and early vascular network formation in the extraembryonic and lateral plate mesoderm territories...
2018: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/29549430/cells-with-hematopoietic-potential-reside-within-mouse-proepicardium
#3
Ewa Jankowska-Steifer, Justyna Niderla-Bielińska, Bogdan Ciszek, Marek Kujawa, Mateusz Bartkowiak, Aleksandra Flaht-Zabost, Daria Klosinska, Anna Ratajska
During embryonic development, hematopoietic cells are present in areas of blood-vessel differentiation. These hematopoietic cells emerge from a specific subpopulation of endothelial cells called the hemogenic endothelium. We have previously found that mouse proepicardium contained its own population of endothelial cells forming a network of vascular tubules. We hypothesize that this EC population contains cells of hematopoietic potential. Therefore, we investigated an in vitro hematopoietic potential of proepicardial cell populations...
March 16, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29530939/regulation-of-runx1-dosage-is-crucial-for-efficient-blood-formation-from-hemogenic-endothelium
#4
Michael Lie-A-Ling, Elli Marinopoulou, Andrew J Lilly, Mairi Challinor, Rahima Patel, Christophe Lancrin, Valerie Kouskoff, Georges Lacaud
During ontogeny, hematopoietic stem and progenitor cells arise from hemogenic endothelium through an endothelial-to-hematopoietic transition that is strictly dependent on the transcription factor RUNX1. Although it is well established that RUNX1 is essential for the onset of hematopoiesis, little is known about the role of RUNX1 dosage specifically in hemogenic endothelium and during the endothelial-to-hematopoietic transition. Here, we used the mouse embryonic stem cell differentiation system to determine if and how RUNX1 dosage affects hemogenic endothelium differentiation...
March 12, 2018: Development
https://www.readbyqxmd.com/read/29467489/a-human-bone-marrow-mesodermal-derived-cell-population-with-hemogenic-potential
#5
Saloomeh Mokhtari, Evan Colletti, Weihong Yin, Chad Sanada, Zanetta Lamar, Paul J Simmons, Steven Walker, Colin Bishop, Anthony Atala, Esmail D Zanjani, Christopher D Porada, Graça Almeida-Porada
The presence, within the human bone marrow, of cells with both endothelial and hemogenic potential has been controversial. Herein, we identify, within the human fetal bone marrow, prior to establishment of hematopoiesis, a unique APLNR+, Stro-1+ cell population, co-expressing markers of early mesodermal precursors and/or hemogenic endothelium. In adult marrow, cells expressing similar markers are also found, but at very low frequency. These adult-derived cells can be extensively culture expanded in vitro without loss of potential, they preserve a biased hemogenic transcriptional profile, and, upon in vitro induction with OCT4, assume a hematopoietic phenotype...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29456178/hoxb4-promotes-hemogenic-endothelium-formation-without-perturbing-endothelial-cell-development
#6
Nadine Teichweyde, Lara Kasperidus, Sebastian Carotta, Valerie Kouskoff, Georges Lacaud, Peter A Horn, Stefan Heinrichs, Hannes Klump
Generation of hematopoietic stem cells (HSCs) from pluripotent stem cells, in vitro, holds great promise for regenerative therapies. Primarily, this has been achieved in mouse cells by overexpression of the homeotic selector protein HOXB4. The exact cellular stage at which HOXB4 promotes hematopoietic development, in vitro, is not yet known. However, its identification is a prerequisite to unambiguously identify the molecular circuits controlling hematopoiesis, since the activity of HOX proteins is highly cell and context dependent...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29386109/a-forward-genetic-screen-targeting-the-endothelium-reveals-a-regulatory-role-for-the-lipid-kinase-pi4ka-in-myelo-and-erythropoiesis
#7
Safiyyah Ziyad, Jesse D Riordan, Ann M Cavanaugh, Trent Su, Gloria E Hernandez, Georg Hilfenhaus, Marco Morselli, Kristine Huynh, Kevin Wang, Jau-Nian Chen, Adam J Dupuy, M Luisa Iruela-Arispe
Given its role as the source of definitive hematopoietic cells, we sought to determine whether mutations initiated in the hemogenic endothelium would yield hematopoietic abnormalities or malignancies. Here, we find that endothelium-specific transposon mutagenesis in mice promotes hematopoietic pathologies that are both myeloid and lymphoid in nature. Frequently mutated genes included previously recognized cancer drivers and additional candidates, such as Pi4ka, a lipid kinase whose mutation was found to promote myeloid and erythroid dysfunction...
January 30, 2018: Cell Reports
https://www.readbyqxmd.com/read/29361566/runx1-is-sufficient-for-blood-cell-formation-from-non-hemogenic-endothelial-cells-in-vivo-only-during-early-embryogenesis
#8
Amanda D Yzaguirre, Elizabeth D Howell, Yan Li, Zijing Liu, Nancy A Speck
Hematopoietic cells differentiate during embryogenesis from a population of endothelial cells called hemogenic endothelium (HE) in a process called the endothelial-to-hematopoietic transition (EHT). The transcription factor Runx1 is required for EHT, but for how long and which endothelial cells are competent to respond to Runx1 are not known. Here, we show that the ability of Runx1 to induce EHT in non-hemogenic endothelial cells depends on the anatomical location of the cell and the developmental age of the conceptus...
January 29, 2018: Development
https://www.readbyqxmd.com/read/29339404/hif-1%C3%AE-and-hif-2%C3%AE-regulate-hemogenic-endothelium-and-hematopoietic-stem-cell-formation-in-zebrafish
#9
Claudia Gerri, Michele Marass, Andrea Rossi, Didier Y R Stainier
During development, hematopoietic stem cells (HSCs) derive from specialized endothelial cells (ECs) called hemogenic endothelium (HE) via a process called endothelial-to-hematopoietic transition (EHT). Hypoxia-inducible factor-1α (HIF-1α) has been reported to positively modulate EHT in vivo, but current data indicate the existence of other regulators of this process. Here we show that in zebrafish, Hif-2α also positively modulates HSC formation. Specifically, HSC marker gene expression is strongly decreased in hif -1aa;hif-1ab ( hif-1α ) and in hif-2aa;hif-2ab ( hif-2α ) zebrafish mutants and morphants...
March 1, 2018: Blood
https://www.readbyqxmd.com/read/29139170/single-cell-resolution-of-human-hemato-endothelial-cells-defines-transcriptional-signatures-of-hemogenic-endothelium
#10
Mathew G Angelos, Juan E Abrahante, Robert H Blum, Dan S Kaufman
Endothelial-to-hematopoietic transition (EHT) is an important stage in definitive hematopoietic development. However, the genetic mechanisms underlying human EHT remains poorly characterized. We performed single cell RNA-seq using 55 hemogenic endothelial cells (HE: CD31(+) CD144(+) CD41(-) CD43(-) CD45(-) CD73(-) RUNX1c(+) ), 47 vascular endothelial cells without hematopoietic potential (non-HE: CD31(+) CD144(+) CD41(-) CD43(-) CD45(-) CD73(-) RUNX1c(-) ), and 35 hematopoietic progenitor cells (HP: CD34(+) CD43(+) RUNX1c(+) ) derived from human embryonic stem cells (hESCs)...
November 15, 2017: Stem Cells
https://www.readbyqxmd.com/read/29073173/notch-activation-is-required-for-downregulation-of-hoxa3-dependent-endothelial-cell-phenotype-during-blood-formation
#11
Valentina Sanghez, Anna Luzzi, Don Clarke, Dustin Kee, Steven Beuder, Danielle Rux, Mitsujiro Osawa, Joaquín Madrenas, Tsui-Fen Chou, Michael Kyba, Michelina Iacovino
Hemogenic endothelium (HE) undergoes endothelial-to-hematopoietic transition (EHT) to generate blood, a process that requires progressive down-regulation of endothelial genes and induction of hematopoietic ones. Previously, we have shown that the transcription factor HoxA3 prevents blood formation by inhibiting Runx1 expression, maintaining endothelial gene expression and thus blocking EHT. In the present study, we show that HoxA3 also prevents blood formation by inhibiting Notch pathway. HoxA3 induced upregulation of Jag1 ligand in endothelial cells, which led to cis-inhibition of the Notch pathway, rendering the HE nonresponsive to Notch signals...
2017: PloS One
https://www.readbyqxmd.com/read/28869683/runx1c-regulates-hematopoietic-differentiation-of-human-pluripotent-stem-cells-possibly-in-cooperation-with-proinflammatory-signaling
#12
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...
November 2017: Stem Cells
https://www.readbyqxmd.com/read/28820341/cell-cycle-dynamics-and-complement-expression-distinguishes-mature-haematopoietic-subsets-arising-from-hemogenic-endothelium
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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