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Huntingtin regulates mammary stem cell division and differentiation

Huntingtin regulates mammary stem cell division and differentiation
Huntingtin regulates mammary stem cell division and differentiation
Little is known about the mechanisms of mitotic spindle orientation during mammary gland morphogenesis. Here, we report the presence of huntingtin, the protein mutated in Huntington’s disease, in mouse mammary basal and luminal cells throughout mammogenesis. Keratin 5-driven depletion of huntingtin results in a decreased pool and specification of basal and luminal progenitors, and altered mammary morphogenesis. Analysis of mitosis in huntingtin-depleted basal progenitors reveals mitotic spindle misorientation. In mammary cell culture, huntingtin regulates spindle orientation in a dynein-dependent manner. Huntingtin is targeted to spindle poles through its interaction with dynein and promotes the accumulation of NUMA and LGN. Huntingtin is also essential for the cortical localization of dynein, dynactin, NUMA, and LGN by regulating their kinesin 1-dependent trafficking along astral microtubules. We thus suggest that huntingtin is a component of the pathway regulating the orientation of mammary stem cell division, with potential implications for their self-renewal and differentiation properties.
2213-6711
491–506
Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3
Thion, Morgane S.
6a1e77c6-3aee-4007-ae5f-4fe2af54e85f
Yu, Hua
39ba379e-83e9-47b7-bffa-d170cf1de9dc
Sousa, Cristavo Marques
ccede927-94df-4aa4-885d-58e7a75c549b
Lasgi, Charlène
d150b37a-5bea-4a52-825a-3cf893b4945f
Morin, Xavier
5e3b7885-7217-49be-831f-2ad439acf367
Humbert, Sandrine
ac49a40c-13aa-4e8e-af65-4b9848862618
Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3
Thion, Morgane S.
6a1e77c6-3aee-4007-ae5f-4fe2af54e85f
Yu, Hua
39ba379e-83e9-47b7-bffa-d170cf1de9dc
Sousa, Cristavo Marques
ccede927-94df-4aa4-885d-58e7a75c549b
Lasgi, Charlène
d150b37a-5bea-4a52-825a-3cf893b4945f
Morin, Xavier
5e3b7885-7217-49be-831f-2ad439acf367
Humbert, Sandrine
ac49a40c-13aa-4e8e-af65-4b9848862618

Elias, Salah, Thion, Morgane S., Yu, Hua, Sousa, Cristavo Marques, Lasgi, Charlène, Morin, Xavier and Humbert, Sandrine (2014) Huntingtin regulates mammary stem cell division and differentiation. Stem Cell Reports, 2 (4), 491–506. (doi:10.1016/j.stemcr.2014.02.011).

Record type: Article

Abstract

Little is known about the mechanisms of mitotic spindle orientation during mammary gland morphogenesis. Here, we report the presence of huntingtin, the protein mutated in Huntington’s disease, in mouse mammary basal and luminal cells throughout mammogenesis. Keratin 5-driven depletion of huntingtin results in a decreased pool and specification of basal and luminal progenitors, and altered mammary morphogenesis. Analysis of mitosis in huntingtin-depleted basal progenitors reveals mitotic spindle misorientation. In mammary cell culture, huntingtin regulates spindle orientation in a dynein-dependent manner. Huntingtin is targeted to spindle poles through its interaction with dynein and promotes the accumulation of NUMA and LGN. Huntingtin is also essential for the cortical localization of dynein, dynactin, NUMA, and LGN by regulating their kinesin 1-dependent trafficking along astral microtubules. We thus suggest that huntingtin is a component of the pathway regulating the orientation of mammary stem cell division, with potential implications for their self-renewal and differentiation properties.

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Accepted/In Press date: 27 February 2014
e-pub ahead of print date: 3 April 2014
Published date: 8 April 2014
Organisations: Biomedicine

Identifiers

Local EPrints ID: 408245
URI: http://eprints.soton.ac.uk/id/eprint/408245
ISSN: 2213-6711
PURE UUID: 13f17b74-6a75-4761-8796-02db5fa913a8

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Date deposited: 18 May 2017 04:01
Last modified: 21 Nov 2021 06:22

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Contributors

Author: Salah Elias
Author: Morgane S. Thion
Author: Hua Yu
Author: Cristavo Marques Sousa
Author: Charlène Lasgi
Author: Xavier Morin
Author: Sandrine Humbert

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