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Cited by 247

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential

Open access
Luchsinger, Larry L., de Almeida, Mariana Justino, Corrigan, David J., Mumau, Melanie, Snoeck, Hans-Willem·2016·Nature

Abstract

Haematopoietic stem cells (HSCs), which sustain production of all blood cell lineages, rely on glycolysis for ATP production, yet little attention has been paid to the role of mitochondria. Here we show in mice that the short isoform of a critical regulator of HSCs, Prdm16 (refs 4, 5), induces mitofusin 2 (Mfn2), a protein involved in mitochondrial fusion and in tethering of mitochondria to the endoplasmic reticulum. Overexpression and deletion studies, including single-cell transplantation assays, revealed that Mfn2 is specifically required for the maintenance of HSCs with extensive lymphoid potential, but not, or less so, for the maintenance of myeloid-dominant HSCs. Mfn2 increased buffering of intracellular Ca2+, an effect mediated through its endoplasmic reticulum–mitochondria tethering activity, thereby negatively regulating nuclear translocation and transcriptional activity of nuclear factor of activated T cells (Nfat). Nfat inhibition rescued the effects of Mfn2 deletion in HSCs, demonstrating that negative regulation of Nfat is the prime downstream mechanism of Mfn2 in the maintenance of HSCs with extensive lymphoid potential. Mitochondria therefore have an important role in HSCs. These findings provide a mechanism underlying clonal heterogeneity among HSCs and may lead to the design of approaches to bias HSC differentiation into desired lineages after transplantation.

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Metadata

Authors
Luchsinger, L. L., de Almeida, M. J., Corrigan, D. J., Mumau, M., & Snoeck, H.-W.
Venue
Nature
Published
2016-01-20
Volume
529
Issue
7587
Pages
528-531
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2295313298
Cited by
247
References
12
FWCI
24.49
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential. https://app.cochat.ai/papers/10.1038/nature16500
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Luchsinger, L. L., de Almeida, M. J., Corrigan, D. J., Mumau, M., & Snoeck, H.-W. (2016). Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential. Nature. https://doi.org/10.1038/nature16500

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