Mouse models of neutropenia reveal progenitor-stage-specific defects

doi:10.1038/s41586-020-2227-7

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2227-7
	Mouse models of neutropenia reveal progenitor-stage-specific defects
	Lombardo, Umberto 1; Iriarte, Jose 2; Hilbert, Lautaro 3; Ruiz-Perez, Javier 4; Capriles, Jose M.5,6; Veit, Heinz 1
	2020-05-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
文章类型	Article;Early Access
语种	英语
国家	USA; Thailand
英文关键词	Advances in genetics and sequencing have identified a plethora of disease-associated and disease-causing genetic alterations. To determine causality between genetics and disease, accurate models for molecular dissection are required however, the rapid expansion of transcriptional populations identified through single-cell analyses presents a major challenge for accurate comparisons between mutant and wild-type cells. Here we generate mouse models of human severe congenital neutropenia (SCN) using patient-derived mutations in the GFI1 transcription factor. To determine the effects of SCN mutations, we generated single-cell references for granulopoietic genomic states with linked epitopes(1), aligned mutant cells to their wild-type equivalents and identified differentially expressed genes and epigenetic loci. We find that GFI1-target genes are altered sequentially, as cells go through successive states of differentiation. These insights facilitated the genetic rescue of granulocytic specification but not post-commitment defects in innate immune effector function, and underscore the importance of evaluating the effects of mutations and therapy within each relevant cell state. Mouse models of severe congenital neutropenia using patient-derived mutations in the GFI1 locus are used to determine the mechanisms by which the disease progresses.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000528161900003
WOS关键词	GFI-1 ; IDENTIFICATION ; NEUTROPHILS ; MUTATIONS ; ELANE ; MICE
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281029
专题	地球科学资源环境科学气候变化
作者单位	1.Univ Bern, Inst Geog, Bern, Switzerland; 2.Univ Exeter, Dept Archaeol, Coll Humanities, Exeter, Devon, England; 3.Univ Sao Paulo, Museu Arqueol & Etnol, Lab Arqueol Trop, Sao Paulo, Brazil; 4.Pompeu Fabra Univ, CaSEs Culture & Socioecol Dynam Res Grp, Barcelona, Spain; 5.Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA; 6.Univ Mayor San Andres, Inst Invest Antropol & Arqueol, La Paz, Bolivia
推荐引用方式 GB/T 7714	Lombardo, Umberto,Iriarte, Jose,Hilbert, Lautaro,et al. Mouse models of neutropenia reveal progenitor-stage-specific defects[J]. NATURE,2020.
APA	Lombardo, Umberto,Iriarte, Jose,Hilbert, Lautaro,Ruiz-Perez, Javier,Capriles, Jose M.,&Veit, Heinz.(2020).Mouse models of neutropenia reveal progenitor-stage-specific defects.NATURE.
MLA	Lombardo, Umberto,et al."Mouse models of neutropenia reveal progenitor-stage-specific defects".NATURE (2020).