A map of transcriptional heterogeneity and regulatory variation in human microglia | Zendy

Adam M. H. Young | Zendy; Natsuhiko Kumasaka | Zendy; Fiona Calvert | Zendy; Timothy R. Hammond | Zendy; Andrew Knights | Zendy; Nikolaos Panousis | Zendy; Jun Sung Park | Zendy; Jeremy Schwartzentruber | Zendy; Jiang Liu | Zendy; Kousik Kundu | Zendy; Michael Segel | Zendy; Natalia A. Murphy | Zendy; Christopher E McMurran | Zendy; Harry Bulstrode | Zendy; Jason Correia | Zendy; Karol P. Budohoski | Zendy; Alexis Joannides | Zendy; Mathew R. Guilfoyle | Zendy; Rikin Trivedi | Zendy; Ramez Kirollos | Zendy; Robert Morris | Zendy; Matthew Garnett | Zendy; Ivan Timofeev | Zendy; Ibrahim Jalloh | Zendy; Katherine Holland | Zendy; Richard Mannion | Zendy; Richard Mair | Zendy; Colin Watts | Zendy; Stephen J. Price | Zendy; Peter J. Kirkpatrick | Zendy; Thomas Santarius | Zendy; Edward Mountjoy | Zendy; Maya Ghoussaini | Zendy; Nicole Soranzo | Zendy; Omer Ali Bayraktar | Zendy; Beth Stevens | Zendy; Peter J. Hutchinson | Zendy; Robin J.M. Franklin | Zendy; Daniel J. Gaffney | Zendy

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A map of transcriptional heterogeneity and regulatory variation in human microglia

Author(s) -

Adam M. H. Young,

Natsuhiko Kumasaka,

Fiona Calvert,

Timothy R. Hammond,

Andrew Knights,

Nikolaos Panousis,

Jun Sung Park,

Jeremy Schwartzentruber,

Jiang Liu,

Kousik Kundu,

Michael Segel,

Natalia A. Murphy,

Christopher E McMurran,

Harry Bulstrode,

Jason Correia,

Karol P. Budohoski,

Alexis Joannides,

Mathew R. Guilfoyle,

Rikin Trivedi,

Ramez Kirollos,

Robert Morris,

Matthew Garnett,

Ivan Timofeev,

Ibrahim Jalloh,

Katherine Holland,

Richard Mannion,

Richard Mair,

Colin Watts,

Stephen J. Price,

Peter J. Kirkpatrick,

Thomas Santarius,

Edward Mountjoy,

Maya Ghoussaini,

Nicole Soranzo,

Omer Ali Bayraktar,

Beth Stevens,

Peter J. Hutchinson,

Robin J.M. Franklin,

Daniel J. Gaffney

Publication year - 2021

Publication title -

nature genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 18.861

H-Index - 573

eISSN - 1546-1718

pISSN - 1061-4036

DOI - 10.1038/s41588-021-00875-2

Subject(s) - biology , microglia , computational biology , variation (astronomy) , genetics , regulatory sequence , regulation of gene expression , gene , evolutionary biology , immunology , inflammation , physics , astrophysics

Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease.

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