Versatile cell ablation tools and their applications to study loss of cell functions

Liu, Fengming; Dai, Sheng; Feng, Dechun; Peng, Xiao; Qin, Zhongnan; Kearns, Alison; Huang, Wenfei; Chen, Yong; Ergün, Süleyman; Wang, Hong; Rappaport, Jay; Bryda, Elizabeth C.; Chandrasekhar, Anand; Aktas, Bertal H.; Hu, Hongzhen; Chang, Sulie L.; Gao, Bin; Qin, Xuebin

doi:10.1007/s00018-019-03243-w

Cited by 24 publications

(18 citation statements)

References 181 publications

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“…ILY, a toxin secreted by Streptococcus intermedius, binds exclusively to hCD59 41,45,46 and, after binding, forms toxin pores that lyse the cells within seconds 27,41,46 . Administration of ILY to ihCD59+ crossed with various Cre-driver lines rapidly and specifically ablates immune and epithelial cells without off-target effects [27][28][29] . The rapidity of the ablation, a unique feature of this model, makes this strategy particularly apt for determining the dynamic regeneration of the targeted cells after ablation [27][28][29]41 .…”

Section: Resultsmentioning

confidence: 99%

“…Administration of ILY to ihCD59+ crossed with various Cre-driver lines rapidly and specifically ablates immune and epithelial cells without off-target effects [27][28][29] . The rapidity of the ablation, a unique feature of this model, makes this strategy particularly apt for determining the dynamic regeneration of the targeted cells after ablation [27][28][29]41 . To specifically and rapidly empty the RMs niche in kidney with minimal off-target effects in other tissues, we chose to inject ILY 30 days after tamoxifen induction in Cx3cr1CreER +/− /ihCD59 +/− mice.…”

Section: Resultsmentioning

confidence: 99%

“…The newly developed lineage-tracing methods have advanced our understanding of the biology of TMs considerably [4][5][6] . Here, we took advantage of the superiority of ILY/ihCD59-mediated rapid cell ablation [27][28][29]41 to map the cell fate of RMs and study the origin and maintenance of RMs niches. We demonstrate that inducibly expressed hCD59 is very stable and can be readily line 42 .…”

Section: Discussionmentioning

confidence: 99%

“…Here, we report the application of a recently generated Creinduced-hCD59 transgenic line (ihCD59) [27][28][29] to trace RMs lineage and determine the fate, dynamics, function, and metabolic states of RMs of BM or embryonic origins. We also couple ihCD59 with rapid ablation of the RMs pool by intermedilysin (ILY) to explore the molecular mechanism underlying RMs niche.…”

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confidence: 99%

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Distinct fate, dynamics and niches of renal macrophages of bone marrow or embryonic origins

et al. 2020

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Renal macrophages (RMs) participate in tissue homeostasis, inflammation and repair. RMs consist of embryo-derived (EMRMs) and bone marrow-derived RMs (BMRMs), but the fate, dynamics, replenishment, functions and metabolic states of these two RM populations remain unclear. Here we investigate and characterize RMs at different ages by conditionally labeling and ablating RMs populations in several transgenic lines. We find that RMs expand and mature in parallel with renal growth after birth, and are mainly derived from fetal liver monocytes before birth, but self-maintain through adulthood with contribution from peripheral monocytes. Moreover, after the RMs niche is emptied, peripheral monocytes rapidly differentiate into BMRMs, with the CX3CR1/CX3CL1 signaling axis being essential for the maintenance and regeneration of both EMRMs and BMRMs. Lastly, we show that EMRMs have a higher capacity for scavenging immune complex, and are more sensitive to immune challenge than BMRMs, with this difference associated with their distinct glycolytic capacities.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Distinct fate, dynamics and niches of renal macrophages of bone marrow or embryonic origins

et al. 2020

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“…Clodronate liposomes can cause local and systemic inflammatory reactions 50,51 , and due to technical reasons, they cannot be repeatedly injected to newborns. We discovered that three injections of αCSF1 antibody alone (started in 10-day-old mice) caused an efficient and prolonged depletion of all testicular macrophages ( Supplementary Fig.…”

Section: Fetal Macrophages Infiltrate the Testes Anlagementioning

confidence: 99%

Generation, localization and functions of macrophages during the development of testis

et al. 2020

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In the testis, interstitial macrophages are thought to be derived from the yolk sac during fetal development, and later replaced by bone marrow-derived macrophages. By contrast, the peritubular macrophages have been reported to emerge first in the postnatal testis and solely represent descendants of bone marrow-derived monocytes. Here, we define new monocyte and macrophage types in the fetal and postnatal testis using high-dimensional single-cell analyses. Our results show that interstitial macrophages have a dominant contribution from fetal liver-derived precursors, while peritubular macrophages are generated already at birth from embryonic precursors. We find that bone marrow-derived monocytes do not substantially contribute to the replenishment of the testicular macrophage pool even after systemic macrophage depletion. The presence of macrophages prenatally, but not postnatally, is necessary for normal spermatogenesis. Our multifaceted data thus challenge the current paradigms in testicular macrophage biology by delineating their differentiation, homeostasis and functions.

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Stable Transgenic Mouse Strain with Enhanced Photoactivatable Cre Recombinase for Spatiotemporal Genome Manipulation

Ying-yin

Qiu

et al. 2022

Advanced Science

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Optogenetic genome engineering is a powerful technology for high-resolution spatiotemporal genetic manipulation, especially for in vivo studies. It is difficult to generate stable transgenic animals carrying a tightly regulated optogenetic system, as its long-term expression induces high background activity. Here, the generation of an enhanced photoactivatable Cre recombinase (ePA-Cre) transgenic mouse strain with stringent light responsiveness and high recombination efficiency is reported. Through serial optimization, ePA-Cre is developed to generate a transgenic mouse line that exhibits 175-fold induction upon illumination. Efficient light-dependent recombination is detected in embryos and various adult tissues of ePA-Cre mice crossed with the Ai14 tdTomato reporter. Importantly, no significant background Cre activity is detected in the tested tissues except the skin. Moreover, efficient light-inducible cell ablation is achieved in ePA-Cre mice crossed with Rosa26-LSL-DTA mice. In conclusion, ePA-Cre mice offer a tightly inducible, highly efficient, and spatiotemporal-specific genome engineering tool for multiple applications.

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Versatile cell ablation tools and their applications to study loss of cell functions

Cited by 24 publications

References 181 publications

Distinct fate, dynamics and niches of renal macrophages of bone marrow or embryonic origins

Distinct fate, dynamics and niches of renal macrophages of bone marrow or embryonic origins

Generation, localization and functions of macrophages during the development of testis

Stable Transgenic Mouse Strain with Enhanced Photoactivatable Cre Recombinase for Spatiotemporal Genome Manipulation

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