scholarly journals Coronary blood vessels from distinct origins converge to equivalent states during mouse and human development

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ragini Phansalkar ◽  
Josephine Krieger ◽  
Mingming Zhao ◽  
Sai Saroja Kolluru ◽  
Robert C Jones ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Cell Fate ◽  
Adult Mouse ◽  
Coronary Vessels ◽  
Lineage Tracing ◽  
Specific Gene ◽  
Functional Differences ◽  
Capillary Endothelial Cells ◽  
Coronary Blood Vessels ◽  
Two Populations

Most cell fate trajectories during development follow a diverging, tree-like branching pattern, but the opposite can occur when distinct progenitors contribute to the same cell type. During this convergent differentiation, it is unknown if cells ‘remember’ their origins transcriptionally or whether this influences cell behavior. Most coronary blood vessels of the heart develop from two different progenitor sources—the endocardium (Endo) and sinus venosus (SV)—but whether transcriptional or functional differences related to origin are retained is unknown. We addressed this by combining lineage tracing with single-cell RNA sequencing (scRNAseq) in embryonic and adult mouse hearts. Shortly after coronary development begins, capillary endothelial cells (ECs) transcriptionally segregated into two states that retained progenitor-specific gene expression. Later in development, when the coronary vasculature is well established but still remodeling, capillary ECs again segregated into two populations, but transcriptional differences were primarily related to tissue localization rather than lineage. Specifically, ECs in the heart septum expressed genes indicative of increased local hypoxia and decreased blood flow. Adult capillary ECs were more homogeneous with respect to both lineage and location. In agreement, SV- and Endo-derived ECs in adult hearts displayed similar responses to injury. Finally, scRNAseq of developing human coronary vessels indicated that the human heart followed similar principles. Thus, over the course of development, transcriptional heterogeneity in coronary ECs is first influenced by lineage, then by location, until heterogeneity declines in the homeostatic adult heart. These results highlight the plasticity of ECs during development, and the validity of the mouse as a model for human coronary development.

scholarly journals Coronary blood vessels from distinct origins converge to equivalent states during mouse and human development

2021 ◽  
Author(s):  
Ragini S Phansalkar ◽  
Josephine Krieger ◽  
Mingming Zhao ◽  
Sai Saroja Kolluru ◽  
Robert C Jones ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Cell Fate ◽  
Adult Mouse ◽  
Coronary Vessels ◽  
Lineage Tracing ◽  
Specific Gene ◽  
Cell Type ◽  
Functional Differences ◽  
Coronary Blood Vessels ◽  
Two Populations

Most cell fate trajectories during development follow a diverging, tree-like branching pattern, but the opposite can occur when distinct progenitors contribute to the same cell type. During this convergent differentiation, it is unknown if cells "remember" their origins transcriptionally or whether this influences cell behavior. Most coronary blood vessels of the heart develop from two different progenitor sources-the endocardium (Endo) and sinus venosus (SV)-but whether transcriptional or functional differences related to origin are retained is unknown. We addressed this by combining lineage tracing with single-cell RNA sequencing (scRNAseq) in embryonic and adult mouse hearts. Shortly after coronary development begins, capillary ECs transcriptionally segregated into two states that retained progenitor-specific gene expression. Later in development, when the coronary vasculature is well-established but still remodeling, capillary ECs again segregated into two populations, but transcriptional differences were related to tissue localization rather than lineage. Specifically, ECs in the heart septum expressed genes indicative of increased local hypoxia and decreased blood flow. Adult capillary ECs were more homogeneous and lacked indications of either lineage or location. In agreement, SV- and Endo-derived ECs in adult hearts displayed similar responses to injury. Finally, scRNAseq of developing human coronary vessels indicated that the human heart followed similar principles. Thus, over the course of development, transcriptional heterogeneity in coronary ECs is first influenced by lineage, then by location, until heterogeneity disappears in the homeostatic adult heart. These results highlight the plasticity of ECs during development, and the validity of the mouse as a model for human coronary development.

scholarly journals Mutual arrangements of coronary blood vessels within the right atrial appendage vestibule.

2021 ◽  
Author(s):  
Jakub Holda ◽  
Katarzyna Słodowska ◽  
Marcin Strona ◽  
Filip Bolechała ◽  
Katarzyna Jasińska ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Complex Analysis ◽  
Coronary Vessels ◽  
Atrial Appendage ◽  
Right Atrial ◽  
Epicardial Surface ◽  
Endocardial Surface ◽  
Coronary Blood Vessels ◽  
Right Atrial Appendage ◽  
The Right

Introduction: The aim of our study was to investigate the presence and mutual relationships of coronary vessels within the right atrial appendage RAA vestibule. Methods and Results: We examined 200 autopsied hearts. The RAA vestibule was cross sectioned along its isthmuses (superior, middle, and inferior). We assessed the presence and mutual relationships between coronary blood vessels. The right coronary artery (RCA) was present in 100% of the superior RAA isthmuses but absent in 2.0% of hearts within the middle isthmus and in 6.5% of hearts within the inferior RAA isthmus. Its diameter was quite uniform along the superior (2.6±0.8mm), middle (2.9±1.1mm) and inferior (2.7±0.9mm) isthmuses (p=0.12). The location of the RCA varied significantly, and it was sometimes accompanied by other accessory coronary vessels. In all the isthmuses, the RCA ran significantly closer to the endocardial surface than to the epicardial surface (p<0.001). At the superior RAA isthmus, the artery was furthest from the right atrial endocardial surface and this distance gradually decreased between the middle RAA isthmus and the inferior RAA isthmus (9.0±4.0 vs. 6.2±3.0 vs. 4.8±2.3mm, respectively; p<0.001). The interposed RCA was found in 7.0% of cases within the superior isthmus, in 2.5% within the middle isthmus and in 1.5% within the inferior isthmus. Conclusions: This study was the most complex analysis of the mutual arrangements and morphometric characteristics of coronary blood vessels within the RAA vestibule. Awareness of additional blood vessels within the vestibule can help clinicians plan and perform safe and efficacious procedures in this region.

scholarly journals Mutual Arrangements of Coronary Blood Vessels within the Right Atrial Appendage Vestibule

2021 ◽  
Vol 10 (16) ◽  
pp. 3588
Author(s):  
Jakub Hołda ◽  
Katarzyna Słodowska ◽  
Marcin Strona ◽  
Karolina Malinowska ◽  
Filip Bolechała ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Complex Analysis ◽  
Coronary Vessels ◽  
Atrial Appendage ◽  
Right Atrial ◽  
Epicardial Surface ◽  
Endocardial Surface ◽  
Coronary Blood Vessels ◽  
Right Atrial Appendage ◽  
The Right

Background: The aim of our study was to investigate the presence and mutual relationships of coronary vessels within the right atrial appendage (RAA) vestibule. Methods: We examined 200 autopsied hearts. The RAA vestibule was cross-sectioned along its isthmuses (superior, middle, and inferior). Results: The right coronary artery (RCA) was present in 100% of the superior RAA isthmuses but absent in 2.0% of hearts within the middle isthmus and in 6.5% of hearts within the inferior RAA isthmus. Its diameter was quite uniform along the superior (2.6 ± 0.8 mm), middle (2.9 ± 1.1 mm), and inferior (2.7 ± 0.9 mm) isthmuses (p = 0.12). The location of the RCA varied significantly, and it was sometimes accompanied by other accessory coronary vessels. In all the isthmuses, the RCA ran significantly closer to the endocardial surface than to the epicardial surface (p < 0.001). At the superior RAA isthmus, the artery was furthest from the right atrial endocardial surface and this distance gradually decreased between the middle RAA isthmus and the inferior RAA. Conclusions: This study was the most complex analysis of the mutual arrangements and morphometric characteristics of coronary blood vessels within the RAA vestibule. Awareness of additional blood vessels within the vestibule can help clinicians plan and perform safe and efficacious procedures in this region.

scholarly journals Distinct Fibroblast Lineages Give Rise to NG2+ Pericyte Populations in Mouse Skin Development and Repair

2021 ◽  
Vol 9 ◽  
Author(s):  
Georgina Goss ◽  
Emanuel Rognoni ◽  
Vasiliki Salameti ◽  
Fiona M. Watt
Keyword(s):  
Blood Vessels ◽  
Adult Mouse ◽  
Mouse Skin ◽  
Cell Types ◽  
Lineage Tracing ◽  
Perivascular Cells ◽  
Skin Development ◽  
Perivascular Cell ◽  
Thickness Skin ◽  
Multiple Cell

We have examined the developmental origins of Ng2+ perivascular cell populations that adhere to the basement membrane of blood vessels, and their contribution to wound healing. Neural/glial antigen 2 (Ng2) labeled most perivascular cells (70–80%) in developing and adult mouse back skin, a higher proportion than expressed by other pericyte markers Tbx18, Nestin and Pdgfrβ. In adult mouse back skin Ng2+ perivascular cells could be categorized into 4 populations based on whether they expressed Pdgfrα and Pdgfrβ individually or in combination or were Pdgfr-negative. Lineage tracing demonstrated that although Ng2+ cells in embryonic and neonatal back skin contributed to multiple cell types they did not give rise to interfollicular fibroblasts within the dermis. Lineage tracing of distinct fibroblast populations during skin development showed that papillary fibroblasts (Lrig1+) gave rise to Ng2+ perivascular cells in the upper dermis, whilst Ng2+ perivascular cells in the lower dermis were primarily derived from reticular Dlk1+ fibroblasts. Following wounding of adult skin, Ng2+ dermal cells only give rise to Ng2+ blood vessel associated cells and did not contribute to other fibroblast lineages. The relative abundance of Ng2+ Pdgfrβ+ perivascular populations was comparable in wounded and non-wounded skin, indicating that perivascular heterogeneity was maintained during full thickness skin repair. In the wound bed Ng2+ perivascular populations were primarily derived from Lrig1+ papillary or Dlk1+ reticular fibroblast lineages, according to the location of the regenerating blood vessels. We conclude that Ng2+ perivascular cells represent a heterogeneous lineage restricted population that is primarily recruited from the papillary or reticular fibroblast lineages during tissue regeneration.

scholarly journals Taking a Step Back: Insights into the Mechanisms Regulating Gut Epithelial Dedifferentiation

2021 ◽  
Vol 22 (13) ◽  
pp. 7043
Author(s):  
Shaida Ouladan ◽  
Alex Gregorieff
Keyword(s):  
Cell Fate ◽  
Hormonal Regulation ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Lineage Tracing ◽  
Intestinal Stem Cells ◽  
Physical Damage ◽  
Epithelial Regeneration ◽  
Gut Epithelium ◽  
Stem Cell Populations

Despite the environmental constraints imposed upon the intestinal epithelium, this tissue must perform essential functions such as nutrient absorption and hormonal regulation, while also acting as a critical barrier to the outside world. These functions depend on a variety of specialized cell types that are constantly renewed by a rapidly proliferating population of intestinal stem cells (ISCs) residing at the base of the crypts of Lieberkühn. The niche components and signals regulating crypt morphogenesis and maintenance of homeostatic ISCs have been intensely studied over the last decades. Increasingly, however, researchers are turning their attention to unraveling the mechanisms driving gut epithelial regeneration due to physical damage or infection. It is now well established that injury to the gut barrier triggers major cell fate changes, demonstrating the highly plastic nature of the gut epithelium. In particular, lineage tracing and transcriptional profiling experiments have uncovered several injury-induced stem-cell populations and molecular markers of the regenerative state. Despite the progress achieved in recent years, several questions remain unresolved, particularly regarding the mechanisms driving dedifferentiation of the gut epithelium. In this review, we summarize the latest studies, primarily from murine models, that define the regenerative processes governing the gut epithelium and discuss areas that will require more in-depth investigation.

scholarly journals Intravital microscopy imaging of kidney injury and regeneration

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yue Liu ◽  
Zongjin Li
Keyword(s):  
Cell Fate ◽  
Intravital Microscopy ◽  
Single Cells ◽  
Elevated Serum ◽  
Kidney Injury ◽  
Lineage Tracing ◽  
Tissue Slices ◽  
Microscopy Imaging ◽  
Two Photon Microscopy ◽  
Nitrogen Levels

AbstractAcute kidney injury (AKI) is a common clinical symptom, which is mainly manifested by elevated serum creatinine and blood urea nitrogen levels. When AKI is not repaired in time, the patient is prone to develop chronic kidney disease (CKD). The kidney is composed of more than 30 different cells, and its structure is complex. It is extremely challenging to understand the lineage relationships and cell fate of these cells in the process of kidney injury and regeneration. Since the 20th century, lineage tracing technology has provided an important mean for studying organ development, tissue damage repair, and the differentiation and fate of single cells. However, traditional lineage tracing methods rely on sacrificing animals to make tissue slices and then take snapshots with conventional imaging tools to obtain interesting information. This method cannot achieve dynamic and continuous monitoring of cell actions on living animals. As a kind of intravital microscopy (IVM), two-photon microscopy (TPM) has successfully solved the above problems. Because TPM has the ability to penetrate deep tissues and can achieve imaging at the single cell level, lineage tracing technology with TPM is gradually becoming popular. In this review, we provided the key technical elements of lineage tracing, and how to use intravital imaging technology to visualize and quantify the fate of renal cells.

scholarly journals Functional Promiscuity of Gene Regulation by Serpentine Receptors in Dictyostelium discoideum

1998 ◽  
Vol 18 (10) ◽  
pp. 5744-5749 ◽  
Author(s):  
Irene Verkerke-Van Wijk ◽  
Ji-Yun Kim ◽  
Raymond Brandt ◽  
Peter N. Devreotes ◽  
Pauline Schaap
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Dictyostelium Discoideum ◽  
Developmental Regulation ◽  
Mutant Cell ◽  
Gene Induction ◽  
Specific Gene ◽  
Wild Type ◽  
Animal Development ◽  
Camp Stimulation

ABSTRACT Serpentine receptors such as smoothened and frizzled play important roles in cell fate determination during animal development. InDictyostelium discoideum, four serpentine cyclic AMP (cAMP) receptors (cARs) regulate expression of multiple classes of developmental genes. To understand their function, it is essential to know whether each cAR is coupled to a specific gene regulatory pathway or whether specificity results from the different developmental regulation of individual cARs. To distinguish between these possibilities, we measured gene induction in car1 car3 double mutant cell lines that express equal levels of either cAR1, cAR2, or cAR3 under a constitutive promoter. We found that all cARs efficiently mediate both aggregative gene induction by cAMP pulses and induction of postaggregative and prespore genes by persistent cAMP stimulation. Two exceptions to this functional promiscuity were observed. (i) Only cAR1 can mediate adenosine inhibition of cAMP-induced prespore gene expression, a phenomenon that was found earlier in wild-type cells. cAR1’s mediation of adenosine inhibition suggests that cAR1 normally mediates prespore gene induction. (ii) Only cAR2 allows entry into the prestalk pathway. Prestalk gene expression is induced by differentiation-inducing factor (DIF) but only after cells have been prestimulated with cAMP. We found that DIF-induced prestalk gene expression is 10 times higher in constitutive cAR2 expressors than in constitutive cAR1 or cAR3 expressors (which still have endogenous cAR2), suggesting that cAR2 mediates induction of DIF competence. Since in wild-type slugs cAR2 is expressed only in anterior cells, this could explain the so far puzzling observations that prestalk cells differentiate at the anterior region but that DIF levels are actually higher at the posterior region. After the initial induction of DIF competence, cAMP becomes a repressor of prestalk gene expression. This function can again be mediated by cAR1, cAR2, and cAR3.

scholarly journals Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lars Velten ◽  
Benjamin A. Story ◽  
Pablo Hernández-Malmierca ◽  
Simon Raffel ◽  
Daniel R. Leonce ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Single Cell ◽  
Lineage Tracing ◽  
Specific Gene ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem ◽  
Mutational Status

AbstractCancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization of these cells remains elusive and with it the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic stem cells (LSCs) underlie mortality but are difficult to isolate due to their low abundance and high similarity to healthy hematopoietic stem cells (HSCs). Here, we demonstrate that LSCs, HSCs, and pre-leukemic stem cells can be identified and molecularly profiled by combining single-cell transcriptomics with lineage tracing using both nuclear and mitochondrial somatic variants. While mutational status discriminates between healthy and cancerous cells, gene expression distinguishes stem cells and progenitor cell populations. Our approach enables the identification of LSC-specific gene expression programs and the characterization of differentiation blocks induced by leukemic mutations. Taken together, we demonstrate the power of single-cell multi-omic approaches in characterizing cancer stem cells.

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