Nature

Mouse lemur cell atlas informs primate genes, physiology and disease

C Camille Ezran S Shixuan Liu S Stephen Chang J Jingsi Ming L Lisbeth A. Guethlein M Michael F. Z. Wang R Roozbeh Dehghannasiri J Julia Olivieri H Hannah K. Frank A Alexander Tarashansky W Winston Koh Q Qiuyu Jing O Olga Botvinnik J Jane Antony M Megan A. Albertelli C Caitlin J. Karanewsky J Jozeph L. Pendleton F Fabienne Aujard M Martine Perret L Liza Shapiro A Andriamahery Razafindrakoto H Hajanirina Noëline Ravelonjanahary P Patricia Wright A Anne D. Yoder C Cathy V. Williams R Robert Schopler U Ute Radespiel J Jean-Michel Verdier C Corinne Lautier E E. Christopher Kirk R Rebecca Lewis K Kerriann M. Casey K Kyle J. Travaglini A Astrid Gillich Z Zicheng Zhao E Elias Godoy J Jérémy Terrien J Jacques Epelbaum D Dita Gratzinger K Katherine Lucot T Thomas Montine J Jessica D’Addabbo I Isaac Bakerman P Patricia Nguyen A Aaron Kershner K Karim Mrouj P Philip Beachy R Rahul Sinha Y Yue Zhang I Irving L. Weissman T Thomas H. Ambrosi M Malachia Hoover A Alina Alam C Charles Chan S SoRi Jang A Avin Veerakumar P Peng Li A Andrea R. Yung C Connor V. Duffy S Song-Lin Ding E Ed S. Lein S Silvana Konermann L Liqun Luo T Trygve E. Bakken J Justus M. Kebschull R Rebecca D. Hodge T Taichi Isobe M Michael F. Clarke A Antoine de Morree B Biter Bilen J Jean Farup A Andoni Urtasun J Jengmin Kang T Thomas A. Rando M Ming Chen B BaoXiang Li V Varun Ramanan Subramaniam S Shravani Mukherjee A Aditi Swarup L Lily Kim B Bronwyn Scott A Ahmad Al-Moujahed A Albert Y. Wu D Douglas Vollrath L Lubert Stryer N Nicholas Schaum A Amanda L. Wiggenhorn T Tony Wyss-Coray Y Yin Liu L Lolita Penland G Gabriel Loeb S Shengda Lin H Honor Paine D Deviana Burhan A Aris Taychameekiatchai S Steven Artandi B Bruce Wang F F. Hernán Espinoza C Christin Kuo R Ross Metzger N Norma Neff Z Zhen Qi R Rebecca Culver K Kerwyn C. Huang P Patrick Neuhöfer C Charles A. Chang Y Yan Hang S Seung K. Kim H Hannah N. W. Weinstein P Paul Allegakoen F Franklin W. Huang S Sivakamasundari V. S Song Eun Lee K Kazuteru Hasegawa H Hosu Sin M Margaret T. Fuller W Wan-Jin Lu A Ankit Baghel W William Kong C Carly Israel R Rene Sit J Jennifer Okamoto A Ashley Maynard M Michelle Tan Y Youcef Ouadah J Jalal Baruni T Timothy Ting-Hsuan Wu R Robert C. Jones M Maurizio Morri S Spyros Darmanis S Sheela Crasta J Jia Yan A Aditi Agrawal S Shelly Huynh B Brian Yu J James Webber J Jia Zhao G Gefei Wang W Weilun Tan S Saba Nafees Z Zhengda Li G Geoff Stanley J Jinxurong Yang S Sheng Wang S Snigdha Agarwal K Kyle Awayan E Erin McGeever V Venkata N. P. Vemuri P Pranav V. Lalgudi A Angela Oliveira Pisco J Jim Karkanias C Can Yang J James E. Ferrell S Scott D. Boyd P Peter Parham J Jonathan Z. Long B Bo Wang J Julia Salzman I Iwijn De Vlaminck A Angela Ruohao Wu S Stephen R. Quake M Mark A. Krasnow

Abstract

Abstract Mouse lemurs (Microcebus spp.) are an emerging primate model organism, but their genetics, cellular and molecular biology remain largely unexplored. In an accompanying paper1, we performed large-scale single-cell RNA sequencing of 27 organs from mouse lemurs. We identified more than 750 molecular cell types, characterized their transcriptomic profiles and provided insight into primate evolution of cell types. Here we use the generated atlas to characterize mouse lemur genes, physiology, disease and mutations. We uncover thousands of previously unidentified lemur genes and hundreds of thousands of new splice junctions including over 85,000 primate splice junctions missing in mice. We systematically explore the lemur immune system by comparing global expression profiles of key immune genes in health and disease, and by mapping immune cell development, trafficking and activation. We characterize primate-specific and lemur-specific physiology and disease, including molecular features of the immune program, lemur adipocytes and metastatic endometrial cancer that resembles the human malignancy. We present expression patterns of more than 400 primate genes missing in mice, many with similar expression patterns to humans and some implicated in human disease. Finally, we provide an experimental framework for reverse genetic analysis by identifying naturally occurring nonsense mutations in three primate immune genes missing in mice and by analysing their transcriptional phenotypes. This work establishes a foundation for molecular and genetic analyses of mouse lemurs and prioritizes primate genes, isoforms, physiology and disease for future study.

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Article Details

Journal Nature
Volume / Issue Vol. 644, Issue 8075
Published August 07, 2025
Pages 185-196
ISSN 0028-0836
Publisher Nature Portfolio

Journal Info

Nature

Nature Portfolio
ISSN: 0028-0836 Health Sciences

Authors (162)

C

Camille Ezran

S

Shixuan Liu

S

Stephen Chang

J

Jingsi Ming

L

Lisbeth A. Guethlein

M

Michael F. Z. Wang

R

Roozbeh Dehghannasiri

J

Julia Olivieri

H

Hannah K. Frank

A

Alexander Tarashansky

W

Winston Koh

Q

Qiuyu Jing

O

Olga Botvinnik

J

Jane Antony

M

Megan A. Albertelli

C

Caitlin J. Karanewsky

J

Jozeph L. Pendleton

F

Fabienne Aujard

M

Martine Perret

L

Liza Shapiro

A

Andriamahery Razafindrakoto

H

Hajanirina Noëline Ravelonjanahary

P

Patricia Wright

A

Anne D. Yoder

C

Cathy V. Williams

R

Robert Schopler

U

Ute Radespiel

J

Jean-Michel Verdier

C

Corinne Lautier

E

E. Christopher Kirk

R

Rebecca Lewis

K

Kerriann M. Casey

K

Kyle J. Travaglini

A

Astrid Gillich

Z

Zicheng Zhao

E

Elias Godoy

J

Jérémy Terrien

J

Jacques Epelbaum

D

Dita Gratzinger

K

Katherine Lucot

T

Thomas Montine

J

Jessica D’Addabbo

I

Isaac Bakerman

P

Patricia Nguyen

A

Aaron Kershner

K

Karim Mrouj

P

Philip Beachy

R

Rahul Sinha

Y

Yue Zhang

I

Irving L. Weissman

T

Thomas H. Ambrosi

M

Malachia Hoover

A

Alina Alam

C

Charles Chan

S

SoRi Jang

A

Avin Veerakumar

P

Peng Li

A

Andrea R. Yung

C

Connor V. Duffy

S

Song-Lin Ding

E

Ed S. Lein

S

Silvana Konermann

L

Liqun Luo

T

Trygve E. Bakken

J

Justus M. Kebschull

R

Rebecca D. Hodge

T

Taichi Isobe

M

Michael F. Clarke

A

Antoine de Morree

B

Biter Bilen

J

Jean Farup

A

Andoni Urtasun

J

Jengmin Kang

T

Thomas A. Rando

M

Ming Chen

B

BaoXiang Li

V

Varun Ramanan Subramaniam

S

Shravani Mukherjee

A

Aditi Swarup

L

Lily Kim

B

Bronwyn Scott

A

Ahmad Al-Moujahed

A

Albert Y. Wu

D

Douglas Vollrath

L

Lubert Stryer

N

Nicholas Schaum

A

Amanda L. Wiggenhorn

T

Tony Wyss-Coray

Y

Yin Liu

L

Lolita Penland

G

Gabriel Loeb

S

Shengda Lin

H

Honor Paine

D

Deviana Burhan

A

Aris Taychameekiatchai

S

Steven Artandi

B

Bruce Wang

F

F. Hernán Espinoza

C

Christin Kuo

R

Ross Metzger

N

Norma Neff

Z

Zhen Qi

R

Rebecca Culver

K

Kerwyn C. Huang

P

Patrick Neuhöfer

C

Charles A. Chang

Y

Yan Hang

S

Seung K. Kim

H

Hannah N. W. Weinstein

P

Paul Allegakoen

F

Franklin W. Huang

S

Sivakamasundari V.

S

Song Eun Lee

K

Kazuteru Hasegawa

H

Hosu Sin

M

Margaret T. Fuller

W

Wan-Jin Lu

A

Ankit Baghel

W

William Kong

C

Carly Israel

R

Rene Sit

J

Jennifer Okamoto

A

Ashley Maynard

M

Michelle Tan

Y

Youcef Ouadah

J

Jalal Baruni

T

Timothy Ting-Hsuan Wu

R

Robert C. Jones

M

Maurizio Morri

S

Spyros Darmanis

S

Sheela Crasta

J

Jia Yan

A

Aditi Agrawal

S

Shelly Huynh

B

Brian Yu

J

James Webber

J

Jia Zhao

G

Gefei Wang

W

Weilun Tan

S

Saba Nafees

Z

Zhengda Li

G

Geoff Stanley

J

Jinxurong Yang

S

Sheng Wang

S

Snigdha Agarwal

K

Kyle Awayan

E

Erin McGeever

V

Venkata N. P. Vemuri

P

Pranav V. Lalgudi

A

Angela Oliveira Pisco

J

Jim Karkanias

C

Can Yang

J

James E. Ferrell

S

Scott D. Boyd

P

Peter Parham

J

Jonathan Z. Long

B

Bo Wang

J

Julia Salzman

I

Iwijn De Vlaminck

A

Angela Ruohao Wu

S

Stephen R. Quake

M

Mark A. Krasnow

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