scholarly journals De novo formation of a distinct coronary vascular population in neonatal heart

Science ◽  
2014 ◽  
Vol 345 (6192) ◽  
pp. 90-94 ◽  
Author(s):  
Xueying Tian ◽  
Tianyuan Hu ◽  
Hui Zhang ◽  
Lingjuan He ◽  
Xiuzhen Huang ◽  
...  
Keyword(s):  
Coronary Circulation ◽  
De Novo ◽  
Coronary Vessels ◽  
Lineage Tracing ◽  
Mouse Heart ◽  
Genetic Lineage ◽  
Substantial Portion ◽  
Vascular Growth ◽  
Cardiovascular Regeneration ◽  
Genetic Lineage Tracing

The postnatal coronary vessels have been viewed as developing through expansion of vessels formed during the fetal period. Using genetic lineage tracing, we found that a substantial portion of postnatal coronary vessels arise de novo in the neonatal mouse heart, rather than expanding from preexisting embryonic vasculature. Our data show that lineage conversion of neonatal endocardial cells during trabecular compaction generates a distinct compartment of the coronary circulation located within the inner half of the ventricular wall. This lineage conversion occurs within a brief period after birth and provides an efficient means of rapidly augmenting the coronary vasculature. This mechanism of postnatal coronary vascular growth provides avenues for understanding and stimulating cardiovascular regeneration following injury and disease.

scholarly journals Evidence for minimal cardiogenic potential of Sca-1 positive cells in the adult mouse heart

2018 ◽  
Author(s):  
Lauren E. Neidig ◽  
Florian Weinberger ◽  
Nathan J. Palpant ◽  
John Mignone ◽  
Amy M. Martinson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Mouse Model ◽  
Lineage Tracing ◽  
Mouse Heart ◽  
Genetic Lineage ◽  
Adult Heart ◽  
New Therapeutic Approaches ◽  
Genetic Lineage Tracing

ABSTRACTBackgroundDespite modern pharmacotherapy, heart failure remains a major medical burden. The heart has a limited regenerative capacity, and bolstering regeneration might represent new therapeutic approaches for heart failure patients. Various progenitor cells in the heart have been proposed to have cardiomyogenic properties, but this evidence is based mostly on cell culture and transplantation studies. One population of interest is characterized by the expression of Stem Cell Antigen-1 (Sca-1). Here we tested the hypothesis that Sca-1+cells are endogenous progenitors for cardiomyocytes in the adult heart.MethodsWe evaluated the innate cardiogenic potential of Sca-1+cellsin vivoby generating a novel mouse model to genetically lineage-trace the fate of Sca-1 expressing cells. This was accomplished by introducing a tamoxifen-inducible Cre-recombinase into the Sca-1 locus (Sca-1mCm/+). Crossing this mouse line to a Cre-dependent tdTomato reporter line allowed for genetic lineage-tracing of endogenous Sca-1+cells (Sca-1mCmR26tdTomato). The frequency of Sca-1+cardiomyocytes was quantified from dispersed cell preparations and confirmed by in situ histology.ResultsWe validated the genetic lineage tracing mouse model in bone marrow and heart. Unlike previous publications suggesting significant cardiogenic potential, we found that less than 0.02% of cardiomyocytes per year were derived from Sca-1+cells in the adult heart under homeostatic conditions. At six months after myocardial infarction, we found less than 0.01% of cardiomyocytes were derived from Sca-1+cells.ConclusionOur results show that Sca-1+cells in the adult heart have minimal cardiogenic potential under homeostatic conditions or in response to myocardial infarction.

scholarly journals The Aging Microenvironment Shapes Alveolar Macrophage Identity in Aging

2019 ◽  
Author(s):  
Alexandra C. McQuattie-Pimentel ◽  
Ziyou Ren ◽  
Nikita Joshi ◽  
Satoshi Watanabe ◽  
Thomas Stoeger ◽  
...  
Keyword(s):  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
The Elderly ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Substantial Portion ◽  
Macrophage Phenotypes ◽  
Genetic Lineage Tracing ◽  
Environmental Challenge ◽  
Severe Lung

AbstractA dysfunctional response to inhaled pathogens and toxins drives a substantial portion of the susceptibility to acute and chronic lung disease in the elderly. We used transcriptomic profiling combined with genetic lineage tracing, heterochronic adoptive transfer, parabiosis and treatment with metformin to show that the lung microenvironment defines the phenotype of long-lived alveolar macrophages during aging. While tissue-resident alveolar macrophages persist in the lung without input from monocytes over the lifespan, severe lung injury results in their replacement with monocyte-derived alveolar macrophages. These monocyte-derived alveolar macrophages are also shaped by the microenvironment both during aging and in response to a subsequent environmental challenge to become transcriptionally and functionally similar to tissue-resident alveolar macrophages. These findings show that changes in alveolar macrophage phenotypes during injury and aging are not cell autonomous but instead are shaped by changes in the aging lung microenvironment.

scholarly journals Restricted differentiative capacity of Wt1-expressing peritoneal mesothelium in postnatal and adult mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas P. Wilm ◽  
Helen Tanton ◽  
Fiona Mutter ◽  
Veronica Foisor ◽  
Ben Middlehurst ◽  
...  
Keyword(s):  
Coronary Vessels ◽  
Intestinal Wall ◽  
Lineage Tracing ◽  
Postnatal Life ◽  
Genetic Lineage ◽  
Peritoneal Mesothelial Cells ◽  
Adult Mice ◽  
Organ Specific ◽  
Genetic Lineage Tracing ◽  
Peritoneal Mesothelium

AbstractPreviously, genetic lineage tracing based on the mesothelial marker Wt1, appeared to show that peritoneal mesothelial cells have a range of differentiative capacities and are the direct progenitors of vascular smooth muscle in the intestine. However, it was not clear whether this was a temporally limited process or continued throughout postnatal life. Here, using a conditional Wt1-based genetic lineage tracing approach, we demonstrate that the postnatal and adult peritoneum covering intestine, mesentery and body wall only maintained itself and failed to contribute to other visceral tissues. Pulse-chase experiments of up to 6 months revealed that Wt1-expressing cells remained confined to the peritoneum and failed to differentiate into cellular components of blood vessels or other tissues underlying the peritoneum. Our data confirmed that the Wt1-lineage system also labelled submesothelial cells. Ablation of Wt1 in adult mice did not result in changes to the intestinal wall architecture. In the heart, we observed that Wt1-expressing cells maintained the epicardium and contributed to coronary vessels in newborn and adult mice. Our results demonstrate that Wt1-expressing cells in the peritoneum have limited differentiation capacities, and that contribution of Wt1-expressing cells to cardiac vasculature is based on organ-specific mechanisms.

scholarly journals Restricted differentiative capacity of Wt1-expressing peritoneal mesothelium in postnatal and adult mice

2020 ◽  
Author(s):  
Thomas P Wilm ◽  
Helen Tanton ◽  
Fiona Mutter ◽  
Veronica Foisor ◽  
Ben Middlehurst ◽  
...  
Keyword(s):  
Coronary Vessels ◽  
Intestinal Wall ◽  
Lineage Tracing ◽  
Postnatal Life ◽  
Genetic Lineage ◽  
Peritoneal Mesothelial Cells ◽  
Adult Mice ◽  
Organ Specific ◽  
Genetic Lineage Tracing ◽  
Peritoneal Mesothelium

AbstractPreviously, genetic lineage tracing based on the mesothelial marker Wt1, appeared to show that peritoneal mesothelial cells have a range of differentiative capacities and are the direct progenitors of vascular smooth muscle in the intestine. However, it was not clear whether this was a temporally limited process or continued throughout postnatal life. Here, using a conditional Wt1-based genetic lineage tracing approach, we demonstrate that the postnatal and adult peritoneum covering intestine, mesentery and body wall only maintained itself and failed to contribute to other visceral tissues. Pulse-chase experiments of up to 6 months revealed that Wt1-expressing cells remained confined to the peritoneum and failed to differentiate into cellular components of blood vessels or other tissues underlying the peritoneum. Ablation of Wt1 in adult mice did not result in changes to the intestinal wall architecture. In the heart, we observed that Wt1-expressing cells maintained the epicardium and contributed to coronary vessels in newborn and adult mice. Our results demonstrate that Wt1-expressing cells in the peritoneum have limited differentiation capacities, and that contribution of Wt1-expressing cells to cardiac vasculature is based on organ-specific mechanisms.

scholarly journals Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart

2016 ◽  
Vol 109 (3) ◽  
pp. 419-430 ◽  
Author(s):  
Lingjuan He ◽  
Qiaozhen Liu ◽  
Tianyuan Hu ◽  
Xiuzhen Huang ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Lineage Tracing ◽  
Main Mechanism ◽  
Mouse Heart ◽  
Genetic Lineage ◽  
Collateral Growth ◽  
Genetic Lineage Tracing

scholarly journals SETD4-expressing cells contribute to pancreatic development and response to cerulein induced pancreatitis injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin-Ze Tian ◽  
Sheng Xing ◽  
Jing-Yi Feng ◽  
Shu-Hua Yang ◽  
Yan-Fu Ding ◽  
...  
Keyword(s):  
Cell Population ◽  
Acinar Cells ◽  
Pancreatic Disease ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Pancreatic Development ◽  
Histone Lysine Methyltransferase ◽  
Population Potential ◽  
Potential Applications ◽  
Genetic Lineage Tracing

AbstractIn the adult pancreas, the presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear. Here, we identify that SET domain-containing protein 4 (SETD4), a histone lysine methyltransferase, is expressed in a small cell population in the adult mouse pancreas. Genetic lineage tracing shows that during pancreatic development, descendants of SETD4+ cells make up over 70% of pancreatic cells and then contribute to each pancreatic lineage during pancreatic homeostasis. SETD4+ cells generate newborn acinar cells in response to cerulein-induced pancreatitis in acinar compartments. Ablation of SETD4+ cells compromises regeneration of acinar cells, in contrast to controls. Our findings provide a new cellular narrative for pancreatic development, homeostasis and response to injury via a small SETD4+ cell population. Potential applications may act to preserve pancreatic function in case of pancreatic disease and/or damage.

Abstract 290: Haemogenic Endocardium Contribute To Definitive Hematopoiesis During Cardiogenesis

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Haruko Nakano ◽  
Xiaoqian Liu ◽  
Armin Arshi ◽  
Ben van Handel ◽  
Rajkumar Sasidharan ◽  
...  
Keyword(s):  
De Novo ◽  
Ex Vivo ◽  
Embryonic Stem ◽  
Circulatory System ◽  
Lineage Tracing ◽  
Mouse Heart ◽  
Heart Tube ◽  
Cardiac Progenitors ◽  
Definitive Hematopoiesis

The circulatory system is the first functional organ system that develops during mammalian life. Accumulating evidences suggest that cardiac and endocardial cells can arise from a single common progenitor cell during mammalian cardiogenesis. Notably, these early cardiac progenitors express multiple hematopoietic transcription factors, consistent with previous reports. Indeed, a close relationship among cardiac, endocardial and hematopoietic lineages has been suggested in fly, zebrafish, and embryonic stem cell in vitro differentiation models. However, it is unclear when, where and how this hematopoietic gene program is in operation during in vivo mammalian cardiogenesis. Hematopoietic colony assay suggests that mouse heart explants generate myeloids and erythroids in the absence of circulation, suggesting that the heart tube is a de novo site for the definitive hematopoiesis. Lineage tracing revealed that putative cardiac-derived Nkx2-5+/Isl1+ endocardial cells give rise to CD41+ hematopoietic progenitors that contribute to definitive hematopoiesis in vivo and ex vivo during embryogenesis earlier than in the AGM region. Furthermore, Nkx2-5 and Isl1 are both required for the hemogenic activity of the endocardium. Together, identification of Nkx2-5/Isl1-dependent hemogenic endocardial cells (1) adds hematopoietic component in the cardiogenesis lineage tree, (2) changes the long-held dogma that AGM is the only major source of definitive hematopoiesis in the embryo proper, and (3) represents phylogenetically conserved fundamental mechanism of cardio-vasculo-hematopoietic differentiation pathway during the development of circulatory system.

scholarly journals Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate

2021 ◽  
Vol 9 ◽  
Author(s):  
Wanbo Tang ◽  
Jian He ◽  
Tao Huang ◽  
Zhijie Bai ◽  
Chaojie Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Hematopoietic Stem Cells ◽  
Fetal Liver ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Hematopoietic Stem ◽  
Genetic Lineage Tracing

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45– and CD45+ pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45– counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45+ E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.

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