Genetic Lineage Tracing of Lymphatic Endothelial Cells in Mice

Martínez-Corral, Inés; Mäkinen, Taija

doi:10.1007/978-1-4939-8712-2_3

Cited by 5 publications

(7 citation statements)

References 52 publications

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“…Conversely, E10.5 tamoxifen administration yields recombination in most E14.5 FL HSCs (Figure 2B,C). Notably, E10.5 Cre induction (performed with 4-OHT, chosen over tamoxifen in this particular experiment because of its more rapid metabolization) [39] avoids targeting the recombination to EMPs in the E11.5 FL (Figure 2D).…”

Section: Transplantation Of Hsc-independent Hematopoietic Progenitors...mentioning

confidence: 99%

Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation

Barone,

Orsenigo,

Cazzola

et al. 2023

Cancers

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Infant acute myeloid leukemia (AML) is a heterogeneous disease, genetically distinct from its adult counterpart. Chromosomal translocations involving the KMT2A gene (MLL) are especially common in affected infants of less than 1 year of age, and are associated with a dismal prognosis. While these rearrangements are likely to arise in utero, the cell of origin has not been conclusively identified. This knowledge could lead to a better understanding of the biology of the disease and support the identification of new therapeutic vulnerabilities. Over the last few years, important progress in understanding the dynamics of fetal hematopoiesis has been made. Several reports have highlighted how hematopoietic stem cells (HSC) provide little contribution to fetal hematopoiesis, which is instead largely sustained by HSC-independent progenitors. Here, we used conditional Cre-Lox transgenic mouse models to engineer the Mll-Af9 translocation in defined subsets of embryonic hematopoietic progenitors. We show that embryonic hematopoiesis is generally permissive for Mll-Af9-induced leukemic transformation. Surprisingly, the selective introduction of Mll-Af9 in HSC-independent progenitors generated a transplantable myeloid leukemia, whereas it did not when introduced in embryonic HSC-derived cells. Ex vivo engineering of the Mll-Af9 rearrangement in HSC-independent progenitors using a CRISPR/Cas9-based approach resulted in the activation of an aberrant myeloid-biased self-renewal program. Overall, our results demonstrate that HSC-independent hematopoietic progenitors represent a permissive environment for Mll-Af9-induced leukemic transformation, and can likely act as cells of origin of infant AML.

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Section: Transplantation Of Hsc-independent Hematopoietic Progenitors...mentioning

confidence: 99%

Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation

Barone,

Orsenigo,

Cazzola

et al. 2023

Cancers

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“…The genetic lineage tracing tools based on cyclization recombinase (Cre) and site-specific locus of x-over, P1 (loxP) homologous recombination elucidate the characteristics of the developmental origin and fate of cells in different organs (4). Cre-loxP provides a new research tool for further revealing the regeneration, homeostasis and pathogenesis of cardiac tissue (5). The regulatory mechanisms of cell origin and fate elucidated the fate and fate plasticity of various cell progeny in humans.…”

Section: Introductionmentioning

confidence: 99%

Cre-loxP-mediated genetic lineage tracing: Unraveling cell fate and origin in the developing heart

Wang

Chen²,

Wang³

et al. 2023

Front. Cardiovasc. Med.

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The Cre-loxP-mediated genetic lineage tracing system is essential for constructing the fate mapping of single-cell progeny or cell populations. Understanding the structural hierarchy of cardiac progenitor cells facilitates unraveling cell fate and origin issues in cardiac development. Several prospective Cre-loxP-based lineage-tracing systems have been used to analyze precisely the fate determination and developmental characteristics of endocardial cells (ECs), epicardial cells, and cardiomyocytes. Therefore, emerging lineage-tracing techniques advance the study of cardiovascular-related cellular plasticity. In this review, we illustrate the principles and methods of the emerging Cre-loxP-based genetic lineage tracing technology for trajectory monitoring of distinct cell lineages in the heart. The comprehensive demonstration of the differentiation process of single-cell progeny using genetic lineage tracing technology has made outstanding contributions to cardiac development and homeostasis, providing new therapeutic strategies for tissue regeneration in congenital and cardiovascular diseases (CVDs).

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“…The discrepancy in the recombination efficiency may be explained by the use of different transgenic Tie2-Cre lines (Kisanuki et al, 2001;Koni et al, 2001). In summary, the existing literature thus provides evidence for both Although Cre/loxP-based lineage tracing is a powerful method for the identification of all progeny produced by a single cell or groups of cells, it has certain notable limitations (Jensen & Dymecki, 2014;Martinez-Corral & Makinen, 2018). For example, constitutive Cre lines do not allow determining temporal lineage contributions and cannot distinguish de novo expression of Cre from a recombination event at an earlier developmental stage.…”

Section: Introductionmentioning

confidence: 99%

“…Although Cre/loxP–based lineage tracing is a powerful method for the identification of all progeny produced by a single cell or groups of cells, it has certain notable limitations ( Jensen & Dymecki, 2014 ; Martinez-Corral & Makinen, 2018 ). For example, constitutive Cre lines do not allow determining temporal lineage contributions and cannot distinguish de novo expression of Cre from a recombination event at an earlier developmental stage.…”

Section: Introductionmentioning

confidence: 99%

Cdh5-lineage–independent origin of dermal lymphatics shown by temporally restricted lineage tracing

et al. 2022

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The developmental origins of lymphatic endothelial cells (LECs) have been under intense research after a century-long debate. Although previously thought to be of solely venous endothelial origin, additional sources of LECs were recently identified in multiple tissues in mice. Here, we investigated the regional differences in the origin(s) of the dermal lymphatic vasculature by lineage tracing using the pan-endothelial Cdh5-CreERT2 line. Tamoxifen-induced labeling of blood ECs at E9.5, before initiation of lymphatic development, traced most of the dermal LECs but with lower efficiency in the lumbar compared with the cervical skin. By contrast, when used at E9.5 but not at E11.5, 4-hydroxytamoxifen, the active metabolite of tamoxifen that provides a tighter window of Cre activity, revealed low labeling frequency of LECs, and lymphvasculogenic clusters in the lumbar skin in particular. Temporally restricted lineage tracing thus reveals contribution of LECs of Cdh5-lineage–independent origin to dermal lymphatic vasculature. Our results further highlight Cre induction strategy as a critical parameter in defining the temporal window for stage-specific lineage tracing during early developmental stages of rapid tissue differentiation.

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Genetic Lineage Tracing of Lymphatic Endothelial Cells in Mice

Cited by 5 publications

References 52 publications

Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation

Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation

Cre-loxP-mediated genetic lineage tracing: Unraveling cell fate and origin in the developing heart

Cdh5-lineage–independent origin of dermal lymphatics shown by temporally restricted lineage tracing

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