Genetic Lineage Tracing of Biliary Epithelial Cells

2018 ◽  
pp. 45-57 ◽  
Author(s):  
Teresa Rubio-Tomás ◽  
Beatriz Aguilar-Bravo ◽  
Pau Sancho-Bru
Keyword(s):  
Epithelial Cells ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Biliary Epithelial Cells ◽  
Genetic Lineage Tracing

scholarly journals Resetting proteostasis with ISRIB prevents pulmonary fibrosis

2020 ◽  
Author(s):  
Satoshi Watanabe ◽  
Nikolay S. Markov ◽  
Ziyan Lu ◽  
Raul Piseaux Aillon ◽  
Saul Soberanes ◽  
...  
Keyword(s):  
Stress Response ◽  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Alveolar Macrophages ◽  
Lineage Tracing ◽  
Alveolar Epithelial Cells ◽  
Genetic Lineage ◽  
Integrated Stress Response ◽  
Alveolar Epithelial ◽  
Genetic Lineage Tracing

AbstractAging is among the most important risk factors for the development of pulmonary fibrosis. We found that a small molecule that specifically inhibits translational inhibition induced by activation of the integrated stress response (ISRIB) attenuated the severity of pulmonary fibrosis in young and old mice. The more severe fibrosis in old compared to young mice was associated with increased recruitment of pathogenic monocyte-derived alveolar macrophages. Using genetic lineage tracing and transcriptomic profiling we found that ISRIB modulates stress response signaling in alveolar epithelial cells resulting in decreased apoptosis and decreased recruitment of pathogenic monocyte-derived alveolar macrophages. These data support multicellular model of fibrosis involving epithelial cells, pathogenic monocyte-derived alveolar macrophages and fibroblasts. Inhibition of the integrated stress response in the aging lung epithelium ameliorates pulmonary fibrosis by preventing the prolonged recruitment of monocyte-derived alveolar macrophages.

scholarly journals Signalling codes for the maintenance and lineage commitment of embryonic gastric epithelial progenitors

Development ◽  
2020 ◽  
Vol 147 (18) ◽  
pp. dev188839
Author(s):  
Sergi Sayols ◽  
Jakub Klassek ◽  
Clara Werner ◽  
Stefanie Möckel ◽  
Sandra Ritz ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Fate ◽  
Ex Vivo ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Gastric Epithelium ◽  
Genetic Lineage ◽  
Genetic Lineage Tracing ◽  
Notch Pathways

ABSTRACTThe identity of embryonic gastric epithelial progenitors is unknown. We used single-cell RNA-sequencing, genetic lineage tracing and organoid assays to assess whether Axin2- and Lgr5-expressing cells are gastric progenitors in the developing mouse stomach. We show that Axin2+ cells represent a transient population of embryonic epithelial cells in the forestomach. Lgr5+ cells generate both glandular corpus and squamous forestomach organoids ex vivo. Only Lgr5+ progenitors give rise to zymogenic cells in culture. Modulating the activity of the WNT, BMP and Notch pathways in vivo and ex vivo, we found that WNTs are essential for the maintenance of Lgr5+ epithelial cells. Notch prevents differentiation of the embryonic epithelial cells along all secretory lineages and hence ensures their maintenance. Whereas WNTs promote differentiation of the embryonic progenitors along the zymogenic cell lineage, BMPs enhance their differentiation along the parietal lineage. In contrast, WNTs and BMPs are required to suppress differentiation of embryonic gastric epithelium along the pit cell lineage. Thus, coordinated action of the WNT, BMP and Notch pathways controls cell fate determination in the embryonic gastric epithelium.

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.

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.

scholarly journals Unraveling the transcriptional networks that drive oligodendrocyte fate specification in Sonic hedgehog-responsive neocortical progenitors

2020 ◽  
Author(s):  
Caitlin C. Winkler ◽  
Luuli N. Tran ◽  
Ellyn P. Milan ◽  
Fernando García-Moreno ◽  
Santos J. Franco
Keyword(s):  
Sonic Hedgehog ◽  
Wild Type Mouse ◽  
Lineage Tracing ◽  
Human Embryos ◽  
Transcriptional Networks ◽  
Genetic Lineage ◽  
Gene Regulatory ◽  
Oligodendrocyte Precursor ◽  
Genetic Lineage Tracing ◽  
Developing Nervous System

In the developing nervous system, progenitors first generate neurons before making astrocytes and oligodendrocytes. We previously showed that increased Sonic hedgehog (Shh) signaling in dorsal forebrain progenitors is important for their production of oligodendrocytes as neurogenesis winds down. Here, we analyzed single-cell RNA sequencing datasets to better understand how Shh controls this neuron-to-oligodendrocyte switch in the neocortex. We first identified Shh-responding progenitors using a dataset in which Shh was overexpressed in the mouse dorsal forebrain. Pseudotime trajectory inferences revealed a subpopulation committed to the oligodendrocyte precursor cell (OPC) lineage. Genes upregulated along this lineage defined a pre-OPC state, as cells transitioned from progenitors to OPCs. Using several datasets from wild-type mouse and human embryos at different ages, we confirmed a pre-OPC state preceding OPC emergence during normal development. Finally, we show that pre-OPCs are enriched for a gene regulatory network involving the transcription factor Ascl1. Genetic lineage-tracing demonstrated Ascl1+ dorsal progenitors primarily make oligodendrocytes. We propose a model in which Shh shifts the balance between opposing transcriptional networks toward an Ascl1 lineage, thereby facilitating the switch between neurogenesis and oligodendrogenesis.

scholarly journals Genetic Lineage Tracing of Sca-1 + Cells Reveals Endothelial but Not Myogenic Contribution to the Murine Heart

Circulation ◽  
2018 ◽  
Vol 138 (25) ◽  
pp. 2931-2939 ◽  
Author(s):  
Ronald J. Vagnozzi ◽  
Michelle A. Sargent ◽  
Suh-Chin J. Lin ◽  
Nathan J. Palpant ◽  
Charles E. Murry ◽  
...  
Keyword(s):  
Lineage Tracing ◽  
Genetic Lineage ◽  
Genetic Lineage Tracing

scholarly journals Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy

2018 ◽  
Vol 115 (4) ◽  
pp. E610-E619 ◽  
Author(s):  
Onur Basak ◽  
Teresa G. Krieger ◽  
Mauro J. Muraro ◽  
Kay Wiebrands ◽  
Daniel E. Stange ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Number ◽  
Lineage Tracing ◽  
Rapid Expansion ◽  
Molecular Signature ◽  
Genetic Lineage ◽  
Proliferating Cells ◽  
Self Renewal ◽  
Genetic Lineage Tracing

The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem-cell number before some return to quiescence. This behavior is best explained by stochastic fate decisions, where stem-cell number within a shared niche fluctuates over time. Fate mapping proliferating cells using a Ki67iresCreER allele confirms that active NSCs reversibly return to quiescence, achieving long-term self-renewal. Our findings suggest a niche-based mechanism for the regulation of NSC fate and number.

scholarly journals Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT

2016 ◽  
Vol 113 (14) ◽  
pp. 3820-3825 ◽  
Author(s):  
Jianjian Zhu ◽  
Kin Ming Kwan ◽  
Susan Mackem
Keyword(s):  
Cell Fate ◽  
Epithelial Mesenchymal Transition ◽  
Primitive Streak ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Mesenchymal Transition ◽  
Neural Fate ◽  
Notochord Cell ◽  
Genetic Lineage Tracing ◽  
And Function

The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial–mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers.

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