Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes

Guibin Chen; Francesca Calcaterra; Yuchi Ma; Xianfeng Ping; Elena Pontarini; Dan Yang; Ferdinando Oriolo; Zhen Yu; Assunta Cancellara; Joanna Mikulak; Yuting Huang; Silvia Della Bella; Yangtengyu Liu; Leslie G. Biesecker; Rebecca L. Harper; Clifton L. Dalgard; Manfred Boehm; Domenico Mavilio

doi:10.1016/j.isci.2023.108331

Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes

Guibin Chen, Francesca Calcaterra, Yuchi Ma, Xianfeng Ping, Elena Pontarini, Dan Yang, Ferdinando Oriolo, Zhen Yu, Assunta Cancellara, Joanna Mikulak, Yuting Huang, Silvia Della Bella, Yangtengyu Liu, Leslie G. Biesecker, Rebecca L. Harper, Clifton L. Dalgard, Manfred Boehm^*, Domenico Mavilio

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

The C-C chemokine receptor type 5 (CCR5) expressed on immune cells supports inflammatory responses by directing cells to the inflammation site. CCR5 is also a major coreceptor for macrophage tropic human immunodeficiency viruses (R5-HIV-1) and its variants can confer protection from HIV infection, making it an ideal candidate to target for therapy. We developed a stepwise protocol that differentiates induced pluripotent stem cells (iPSCs) from individuals homozygous for the CCR5Δ32 variant and healthy volunteers into myeloid lineage induced monocytes (iMono) and macrophages (iMac). By characterizing iMono and iMac against their primary counterparts, we demonstrated that CCR5Δ32 homozygous cells are endowed with similar pluripotent potential for self-renewal and differentiation as iPSC lines generated from non-variant individuals while also showing resistance to HIV infection. In conclusion, these cells are a platform to investigate CCR5 pathophysiology in HIV-positive and negative individuals and to help develop novel therapies.

Original language	English
Article number	108331
Journal	iScience
Volume	26
Issue number	11
DOIs	https://doi.org/10.1016/j.isci.2023.108331
State	Published - 17 Nov 2023
Externally published	Yes

Keywords

Immunology
Molecular biology
Stem cells research

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10.1016/j.isci.2023.108331

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Chen, G., Calcaterra, F., Ma, Y., Ping, X., Pontarini, E., Yang, D., Oriolo, F., Yu, Z., Cancellara, A., Mikulak, J., Huang, Y., Della Bella, S., Liu, Y., Biesecker, L. G., Harper, R. L., Dalgard, C. L., Boehm, M., & Mavilio, D. (2023). Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes. iScience, 26(11), Article 108331. https://doi.org/10.1016/j.isci.2023.108331

@article{a31eb16ddd8a4aa4b4fa2385d9bcf4b3,

title = "Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes",

abstract = "The C-C chemokine receptor type 5 (CCR5) expressed on immune cells supports inflammatory responses by directing cells to the inflammation site. CCR5 is also a major coreceptor for macrophage tropic human immunodeficiency viruses (R5-HIV-1) and its variants can confer protection from HIV infection, making it an ideal candidate to target for therapy. We developed a stepwise protocol that differentiates induced pluripotent stem cells (iPSCs) from individuals homozygous for the CCR5Δ32 variant and healthy volunteers into myeloid lineage induced monocytes (iMono) and macrophages (iMac). By characterizing iMono and iMac against their primary counterparts, we demonstrated that CCR5Δ32 homozygous cells are endowed with similar pluripotent potential for self-renewal and differentiation as iPSC lines generated from non-variant individuals while also showing resistance to HIV infection. In conclusion, these cells are a platform to investigate CCR5 pathophysiology in HIV-positive and negative individuals and to help develop novel therapies.",

keywords = "Immunology, Molecular biology, Stem cells research",

author = "Guibin Chen and Francesca Calcaterra and Yuchi Ma and Xianfeng Ping and Elena Pontarini and Dan Yang and Ferdinando Oriolo and Zhen Yu and Assunta Cancellara and Joanna Mikulak and Yuting Huang and {Della Bella}, Silvia and Yangtengyu Liu and Biesecker, {Leslie G.} and Harper, {Rebecca L.} and Dalgard, {Clifton L.} and Manfred Boehm and Domenico Mavilio",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = nov,

day = "17",

doi = "10.1016/j.isci.2023.108331",

language = "English",

volume = "26",

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Chen, G, Calcaterra, F, Ma, Y, Ping, X, Pontarini, E, Yang, D, Oriolo, F, Yu, Z, Cancellara, A, Mikulak, J, Huang, Y, Della Bella, S, Liu, Y, Biesecker, LG, Harper, RL, Dalgard, CL, Boehm, M & Mavilio, D 2023, 'Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes', iScience, vol. 26, no. 11, 108331. https://doi.org/10.1016/j.isci.2023.108331

TY - JOUR

T1 - Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes

AU - Chen, Guibin

AU - Calcaterra, Francesca

AU - Ma, Yuchi

AU - Ping, Xianfeng

AU - Pontarini, Elena

AU - Yang, Dan

AU - Oriolo, Ferdinando

AU - Yu, Zhen

AU - Cancellara, Assunta

AU - Mikulak, Joanna

AU - Huang, Yuting

AU - Della Bella, Silvia

AU - Liu, Yangtengyu

AU - Biesecker, Leslie G.

AU - Harper, Rebecca L.

AU - Dalgard, Clifton L.

AU - Boehm, Manfred

AU - Mavilio, Domenico

PY - 2023/11/17

Y1 - 2023/11/17

N2 - The C-C chemokine receptor type 5 (CCR5) expressed on immune cells supports inflammatory responses by directing cells to the inflammation site. CCR5 is also a major coreceptor for macrophage tropic human immunodeficiency viruses (R5-HIV-1) and its variants can confer protection from HIV infection, making it an ideal candidate to target for therapy. We developed a stepwise protocol that differentiates induced pluripotent stem cells (iPSCs) from individuals homozygous for the CCR5Δ32 variant and healthy volunteers into myeloid lineage induced monocytes (iMono) and macrophages (iMac). By characterizing iMono and iMac against their primary counterparts, we demonstrated that CCR5Δ32 homozygous cells are endowed with similar pluripotent potential for self-renewal and differentiation as iPSC lines generated from non-variant individuals while also showing resistance to HIV infection. In conclusion, these cells are a platform to investigate CCR5 pathophysiology in HIV-positive and negative individuals and to help develop novel therapies.

AB - The C-C chemokine receptor type 5 (CCR5) expressed on immune cells supports inflammatory responses by directing cells to the inflammation site. CCR5 is also a major coreceptor for macrophage tropic human immunodeficiency viruses (R5-HIV-1) and its variants can confer protection from HIV infection, making it an ideal candidate to target for therapy. We developed a stepwise protocol that differentiates induced pluripotent stem cells (iPSCs) from individuals homozygous for the CCR5Δ32 variant and healthy volunteers into myeloid lineage induced monocytes (iMono) and macrophages (iMac). By characterizing iMono and iMac against their primary counterparts, we demonstrated that CCR5Δ32 homozygous cells are endowed with similar pluripotent potential for self-renewal and differentiation as iPSC lines generated from non-variant individuals while also showing resistance to HIV infection. In conclusion, these cells are a platform to investigate CCR5 pathophysiology in HIV-positive and negative individuals and to help develop novel therapies.

KW - Immunology

KW - Molecular biology

KW - Stem cells research

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U2 - 10.1016/j.isci.2023.108331

DO - 10.1016/j.isci.2023.108331

M3 - Article

AN - SCOPUS:85176234459

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 11

M1 - 108331

ER -

Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes

Abstract

Keywords

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