scholarly journals Tfap2b specifies an embryonic melanocyte stem cell population that retains adult multi-fate potential

2021 ◽  
Author(s):  
Alessandro Brombin ◽  
Daniel J. Simpson ◽  
Jana Travnickova ◽  
Hannah R. Brunsdon ◽  
Zhiqiang Zeng ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Crest ◽  
Pigment Cell ◽  
Cell Types ◽  
Lineage Tracing ◽  
Stem Cell Population ◽  
Cell Of Origin ◽  
Lineage Markers ◽  
Melanocyte Stem Cell ◽  
Stem Cell Populations

Melanocytes, our pigment producing cells, originate from neural crest-derived progenitors during embryogenesis and from multiple stem cell niches in adult tissues. Although pigmentation traits are known risk-factors for melanoma, we lack lineage markers with which to identify melanocyte stem cell populations and study their function. Here, by combining live-imaging, scRNA-seq and chemical-genetics in zebrafish, we identify the transcription factor Tfap2b as a functional marker for the melanocyte stem cell (MSC) population that resides at the dorsal root ganglia site. Tfap2b is required for only a few late-stage embryonic melanocytes, and instead is essential for MSC-dependent melanocyte regeneration. Our lineage-tracing data reveal that tfap2b-expressing MSCs have multi-fate potential, and are the cell-of-origin for a discrete number of embryonic melanocytes, large patches of adult melanocytes, and two other pigment cell types; iridophores and xanthophores. Hence, Tfap2b confers MSC identity, and thereby distinguishes MSCs from other neural crest and pigment cell lineages.

scholarly journals Identification of a human adult cardiac stem cell population with neural crest origin

2019 ◽  
Author(s):  
Anna Höving ◽  
Madlen Merten ◽  
Kazuko Elena Schmidt ◽  
Isabel Faust ◽  
Lucia Mercedes Ruiz-Perera ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Crest ◽  
Cell Population ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Cardiac Stem Cell ◽  
Adult Human ◽  
Neural Crest Origin ◽  
Stem Cell Populations

ABSTRACTCardiovascular diseases are the major cause of death worldwide, emphasizing the necessity to better understand adult human cardiac cell biology and development. Although the adult heart was considered as a terminally differentiated organ, rare populations of cardiac stem cells (CSCs) have been described so far, with their developmental origin and endogenous function still being a matter of debate.Here, we identified a Nestin+/S100+/CD105+/Sca1+/cKit-population of CSCs in the myocardium of the adult human heart auricle. Isolated cells showed expression of characteristic neural crest-derived stem cell (NCSC) markers and kept their genetic stability during cultivationin vitro. Cultivated hCSCs efficiently gave rise to functional, beating cardiomyocytes, osteoblasts, adipocytes and neurons. Global transcriptome analysis via RNAseq showed a high similarity between the expression profiles of Nestin+/S100+/CD105+/Sca1+/cKit-hCSCs and adult human NCSCs from the nasal cavity (inferior turbinate stem cells, ITSCs). In detail, 88.1 % of all genes were significantly expressed in both stem cell populations particularly including common NCSC-markers. Based on these observations, we suggest a similar developmental origin of both stem cell populations.In summary, we identified a human adult cardiac stem cell population with neural crest-origin, which may also contribute to endogenous cardiac tissue homeostasis and tissue repairin vivo.

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 NG2 Proteoglycan Expression in Mouse Skin: Altered Postnatal Skin Development in the NG2 Null Mouse

2007 ◽  
Vol 56 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Kuniko Kadoya ◽  
Jun-ichi Fukushi ◽  
Yoshihiro Matsumoto ◽  
Yu Yamaguchi ◽  
William B. Stallcup
Keyword(s):  
Stem Cell ◽  
Mouse Skin ◽  
Hair Follicles ◽  
Stem Cell Population ◽  
Null Mouse ◽  
Outer Root Sheath ◽  
Skin Development ◽  
Bulge Region ◽  
Ng2 Proteoglycan ◽  
Stem Cell Populations

In early postnatal mouse skin, the NG2 proteoglycan is expressed in the subcutis, the dermis, the outer root sheath of hair follicles, and the basal keratinocyte layer of the epidermis. With further development, NG2 is most prominently expressed by stem cells in the hair follicle bulge region, as also observed in adult human skin. During telogen and anagen phases of the adult hair cycle, NG2 is also found in stem cell populations that reside in dermal papillae and the outer root sheaths of hair follicles. Ablation of NG2 produces alterations in both the epidermis and subcutis layers of neonatal skin. Compared with wild type, the NG2 null epidermis does not achieve its full thickness due to reduced proliferation of basal keratinocytes that serve as the stem cell population in this layer. Thickening of the subcutis is also delayed in NG2 null skin due to deficiencies in the adipocyte population.

scholarly journals The Adipose-derived Stem Cell: Looking Back and Looking Ahead

2010 ◽  
Vol 21 (11) ◽  
pp. 1783-1787 ◽  
Author(s):  
Patricia A. Zuk
Keyword(s):  
Stem Cell ◽  
Historical Perspective ◽  
Es Cells ◽  
Adult Stem Cell ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Stem Cell Populations ◽  
New Applications ◽  
Adipose Derived Stem Cell ◽  
Looking Back

In 2002, researchers at UCLA published a manuscript in Molecular Biology of the Cell describing a novel adult stem cell population isolated from adipose tissue—the adipose-derived stem cell (ASC). Since that time, the ASC has gone on to be one of the most popular adult stem cell populations currently being used in the stem cell field. With multilineage mesodermal potential and possible ectodermal and endodermal potentials also, the ASC could conceivably be an alternate to pluripotent ES cells in both the lab and in the clinic. In this retrospective article, a historical perspective on the ASC is given together with exciting new applications for the stem cell being considered today.

scholarly journals Cellular and molecular characterization of the role of the flk-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2422-2430 ◽  
Author(s):  
FC Zeigler ◽  
BD Bennett ◽  
CT Jordan ◽  
SD Spencer ◽  
S Baumhueter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Hematopoietic Stem Cell ◽  
Receptor Tyrosine Kinase ◽  
Lymphoid Cells ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Stem Cell Populations

The flk-2/flt-3 receptor tyrosine kinase was cloned from a hematopoietic stem cell population and is considered to play a potential role in the developmental fate of the stem cell. Using antibodies derived against the extracellular domain of the receptor, we show that stem cells from both murine fetal liver and bone marrow can express flk-2/flt-3. However, in both these tissues, there are stem cell populations that do not express the receptor. Cell cycle analysis shows that stem cells that do not express the receptor have a greater percentage of the population in G0 when compared with the flk-2/flt-3- positive population. Development of agonist antibodies to the receptor shows a proliferative role for the receptor in stem cell populations. Stimulation with an agonist antibody gives rise to an expansion of both myeloid and lymphoid cells and this effect is enhanced by the addition of kit ligand. These studies serve to further illustrate the importance of the flk-2/flt-3 receptor in the regulation of the hematopoietic stem cell.

Common precursors for neural and mesectodermal derivatives in the cephalic neural crest

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 301-305 ◽  
Author(s):  
A. Baroffio ◽  
E. Dupin ◽  
N.M. Le Douarin
Keyword(s):  
Neural Crest ◽  
Cell Types ◽  
Culture Conditions ◽  
Pigment Cells ◽  
Stem Cell Population ◽  
Multipotent Cells ◽  
Clonal Cultures ◽  
Vertebrate Embryos ◽  
Derivatives Of

The cephalic neural crest (NC) of vertebrate embryos yields a variety of cell types belonging to the neuronal, glial, melanocytic and mesectodermal lineages. Using clonal cultures of quail migrating cephalic NC cells, we demonstrated that neurons and glial cells of the peripheral nervous system can originate from the same progenitors as cartilage, one of the mesectodermal derivatives of the NC. Moreover, we obtained evidence that the migrating cephalic NC contains a few highly multipotent precursors that are common to neurons, glia, cartilage and pigment cells and which we interprete as representative of a stem cell population. In contrast, other NC cells, although provided with identical culture conditions, give rise to clones composed of only one or some of these cell types. These cells thus appear restricted in their developmental potentialities compared to multipotent cells. It is therefore proposed that, in vivo, the active proliferation of pluripotent NC cells during the migration process generates distinct subpopulations of cells that become progressively committed to different developmental fates.

scholarly journals Cells expressing PAX8 are the main source of homeostatic regeneration of adult mouse endometrial epithelium and give rise to serous endometrial carcinoma

2020 ◽  
Vol 13 (10) ◽  
pp. dmm047035
Author(s):  
Dah-Jiun Fu ◽  
Andrea J. De Micheli ◽  
Mallikarjun Bidarimath ◽  
Lora H. Ellenson ◽  
Benjamin D. Cosgrove ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Endometrial Carcinoma ◽  
Marrow Cell ◽  
Cell Types ◽  
Lineage Tracing ◽  
Cell Of Origin ◽  
Mouse Uterus ◽  
Endometrial Epithelium

ABSTRACTHumans and mice have cyclical regeneration of the endometrial epithelium. It is expected that such regeneration is ensured by tissue stem cells, but their location and hierarchy remain debatable. A number of recent studies have suggested the presence of stem cells in the mouse endometrial epithelium. At the same time, it has been reported that this tissue can be regenerated by stem cells of stromal/mesenchymal or bone marrow cell origin. Here, we describe a single-cell transcriptomic atlas of the main cell types of the mouse uterus and epithelial subset transcriptome and evaluate the contribution of epithelial cells expressing the transcription factor PAX8 to the homeostatic regeneration and malignant transformation of adult endometrial epithelium. According to lineage tracing, PAX8+ epithelial cells are responsible for long-term maintenance of both luminal and glandular epithelium. Furthermore, multicolor tracing shows that individual glands and contiguous areas of luminal epithelium are formed by clonal cell expansion. Inactivation of the tumor suppressor genes Trp53 and Rb1 in PAX8+ cells, but not in FOXJ1+ cells, leads to the formation of neoplasms with features of serous endometrial carcinoma, one of the most aggressive types of human endometrial malignancies. Taken together, our results show that the progeny of single PAX8+ cells represents the main source of regeneration of the adult endometrial epithelium. They also provide direct experimental genetic evidence for the key roles of the P53 and RB pathways in the pathogenesis of serous endometrial carcinoma and suggest that PAX8+ cells represent the cell of origin of this neoplasm.

scholarly journals Profiling proliferative cells and their progeny in damaged murine hearts

2018 ◽  
Vol 115 (52) ◽  
pp. E12245-E12254 ◽  
Author(s):  
Kai Kretzschmar ◽  
Yorick Post ◽  
Marie Bannier-Hélaouët ◽  
Andrea Mattiotti ◽  
Jarno Drost ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Cardiac Fibroblasts ◽  
Cardiac Injury ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Postnatal Growth ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Proliferating Cells

The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury.

Role of Notch Signaling in Hematopoietic Stem Cell Function

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-15-SCI-15
Author(s):  
Lluis Espinosa ◽  
Anna Bigas
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Conflicts Of Interest ◽  
Notch Pathway ◽  
Cell Types ◽  
Loss Of Function ◽  
Hematopoietic Stem ◽  
On Chip ◽  
Stem Cell Populations

Abstract Abstract SCI-15 The Notch pathway controls the generation of different cell types in most tissues including blood, and dysregulation of this pathway is strongly associated with oncogenic processes. In many systems, Notch is also required for the maintenance of the stem cell populations. However, in the adult hematopoietic system this link between Notch and stemness has not been established. Instead, work of several groups, including ours, has clearly demonstrated that Notch has a prominent role in the generation of hematopoietic stem cells (HSC) during embryonic development. Although the first wave of blood cells appears in the mouse embryo around day 7.5 of development and is independent of Notch function, embryonic HSC are formed around day 10 of development from endothelial-like progenitors that reside in the embryonic aorta surrounded by the gonad and mesonephros, also called AGM region. By analyzing different Notch pathway mutant mouse embryos, we have demonstrated the involvement of the Jagged1-Notch1-GATA2 axis in this event. However, the formal demonstration that Notch regulates the GATA2 gene during HSC generation is still lacking. We have now found that GATA2 is a direct Notch target in vivo during embryonic HSC generation. However, whereas Notch positively activates GATA2 transcription in the HSC precursors, it simultaneously activates hes1 transcription, which acts a repressor of the same GATA2 gene. This finding directly implicates hes1 in the regulation of HSC development although further studies using loss-of-function mutant embryos are still needed. Altogether, our results indicate that both Notch and hes1 are required to finely regulate the levels, distribution, and likely the timing of GATA2 expression through an incoherent feed-forward loop. In parallel, we have identified other downstream targets of Notch in the AGM region by ChIP-on-chip and expression microarray analysis that we are currently characterizing. Disclosures: No relevant conflicts of interest to declare.

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