KIT D816V Mast Cells Derived from Induced Pluripotent Stem Cells Recapitulate Systemic Mastocytosis Transcriptional Profile

被引：6

作者：

de Toledo, Marcelo A. S. ^{[1
,2
,3
,4
]}

Fu, Xuhuang ^{[1
,2
]}

Maie, Tiago ^{[5
]}

Buhl, Eva M. ^{[6
]}

Goetz, Katrin ^{[1
,2
]}

Schmitz, Susanne ^{[1
,2
]}

Kaiser, Anne ^{[3
,4
]}

Boor, Peter ^{[6
]}

Braunschweig, Till ^{[6
]}

Chatain, Nicolas ^{[3
,4
]}

Costa, Ivan G. ^{[5
]}

Bruemmendorf, Tim H. ^{[3
,4
]}

Koschmieder, Steffen ^{[3
,4
]}

Zenke, Martin ^{[1
,2
,3
,4
]}

机构：

[1] Rhein Westfal TH Aachen, Inst Biomed Engn, Dept Cell Biol, Sch Med, D-52074 Aachen, Germany

[2] Rhein Westfal TH Aachen, Helmholtz Inst Biomed Engn, D-52074 Aachen, Germany

[3] Rhein Westfal TH Aachen, Dept Hematol Oncol Hemostaseol & Stem Cell Transp, Sch Med, D-52074 Aachen, Germany

[4] Ctr Integrated Oncol Aachen Bonn Cologne Dusseldo, D-52074 Aachen, Germany

[5] Rhein Westfal TH Aachen, Inst Computat Genom, Sch Med, D-52074 Aachen, Germany

[6] Rhein Westfal TH Aachen, Inst Pathol, Elect Microscopy Facil, Sch Med, D-52074 Aachen, Germany

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 06期

关键词：

mast cell; systemic mastocytosis; KIT D816V; induced pluripotent stem cell; disease modeling; RNA-seq; iPS cell differentiation protocol; I EXPRESSION; MOUSE MODEL; BLOOD; LINEAGE; RELEASE; DEGRANULATION; REGULATORS; MUTATIONS; MEDIATORS; HISTAMINE;

D O I：

10.3390/ijms24065275

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mast cells (MCs) represent a population of hematopoietic cells with a key role in innate and adaptive immunity and are well known for their detrimental role in allergic responses. Yet, MCs occur in low abundance, which hampers their detailed molecular analysis. Here, we capitalized on the potential of induced pluripotent stem (iPS) cells to give rise to all cells in the body and established a novel and robust protocol for human iPS cell differentiation toward MCs. Relying on a panel of systemic mastocytosis (SM) patient-specific iPS cell lines carrying the KIT D816V mutation, we generated functional MCs that recapitulate SM disease features: increased number of MCs, abnormal maturation kinetics and activated phenotype, CD25 and CD30 surface expression and a transcriptional signature characterized by upregulated expression of innate and inflammatory response genes. Therefore, human iPS cell-derived MCs are a reliable, inexhaustible, and close-to-human tool for disease modeling and pharmacological screening to explore novel MC therapeutics.

引用

页数：18

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