Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

被引：205

作者：

Eraslan, Gokcen ^{[1
,15
]}

Drokhlyansky, Eugene ^{[1
]}

Anand, Shankara ^{[2
]}

Fiskin, Evgenij ^{[1
]}

Subramanian, Ayshwarya ^{[1
]}

Slyper, Michal ^{[1
]}

Wang, Jiali ^{[3
,4
,5
]}

Van Wittenberghe, Nicholas ^{[1
]}

Rouhana, John M. ^{[3
,4
,5
]}

Waldman, Julia ^{[1
]}

Ashenberg, Orr ^{[1
]}

Lek, Monkol ^{[6
]}

Dionne, Danielle ^{[1
]}

Win, Thet Su ^{[7
]}

Cuoco, Michael S. ^{[1
]}

Kuksenko, Olena ^{[1
]}

Tsankov, Alexander M. ^{[8
]}

Branton, Philip A. ^{[9
]}

Marshall, Jamie L. ^{[2
]}

Greka, Anna ^{[2
,10
]}

Getz, Gad ^{[2
,11
,12
,13
]}

Segre, Ayellet, V ^{[3
,4
,5
]}

Aguet, Francois ^{[2
,16
]}

Rozenblatt-Rosen, Orit ^{[1
,15
]}

Ardlie, Kristin G. ^{[2
]}

Regev, Aviv ^{[1
,14
,15
]}

机构：

[1] Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[3] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA

[4] Harvard Med Sch, Ocular Genom Inst, Massachusetts Eye & Ear, Dept Ophthalmol, Boston, MA 02114 USA

[5] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA 02142 USA

[6] Yale Sch Med, Dept Genet, New Haven, CT 06510 USA

[7] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA

[8] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[9] Joint Pathol Ctr Gynecol Breast Pathol, Silver Spring, MD 20910 USA

[10] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[11] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[12] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[13] Harvard Med Sch, Boston, MA 02115 USA

[14] MIT, Dept Biol, Cambridge, MA 02139 USA

[15] Genentech Inc, San Francisco, CA 94080 USA

[16] Illumina Inc, Illumina Artificial Intelligence Lab, San Diego, CA 92121 USA

来源：

SCIENCE | 2022年 / 376卷 / 6594期

基金：

美国国家卫生研究院;

关键词：

RNA-SEQ; FRASER-SYNDROME; PROTEIN NEPHRONECTIN; BLEBBED PHENOTYPE; SKELETAL-MUSCLE; MOUSE MODEL; CELL; EXPRESSION; MUTATION; SUBSETS;

D O I：

10.1126/science.abl4290

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratorymethods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissuespecific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.

引用

页码：712 / +

页数：137

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