Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo

被引：139

作者：

Rongvaux, Anthony ^{[1
,2
]}

Willinger, Tim ^{[1
,2
]}

Takizawa, Hitoshi ^{[1
,4
,5
]}

Rathinam, Chozhavendan ^{[1
,2
]}

Auerbach, Wojtek ^{[6
]}

Murphy, Andrew J. ^{[6
]}

Valenzuela, David M. ^{[6
]}

Yancopoulos, George D. ^{[6
]}

Eynon, Elizabeth E. ^{[1
,2
,3
]}

Stevens, Sean ^{[1
,6
]}

Manz, Markus G. ^{[1
,4
,5
]}

Flavell, Richard A. ^{[1
,2
,3
]}

机构：

[1] Yale Univ, Sch Med, Bill & Melinda Gates Fdn Grand Challenges Global, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA

[3] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA

[4] Univ Zurich Hosp, Div Hematol, CH-8091 Zurich, Switzerland

[5] Biomed Res Inst, CH-6500 Bellinzona, Switzerland

[6] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 06期

关键词：

C-MPL LIGAND; SCID-HU MOUSE; STEM-CELLS; IMMUNE-SYSTEM; CORD BLOOD; IDENTIFICATION; PROGENITORS; ENGRAFTMENT; EXPRESSION; MEGAKARYOCYTOPOIESIS;

D O I：

10.1073/pnas.1019524108

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：

Hematopoietic stem cells (HSCs) both self-renew and give rise to all blood cells for the lifetime of an individual. Xenogeneic mouse models are broadly used to study human hematopoietic stem and progenitor cell biology in vivo. However, maintenance, differentiation, and function of human hematopoietic cells are suboptimal in these hosts. Thrombopoietin (TPO) has been demonstrated as a crucial cytokine supporting maintenance and self-renewal of HSCs. We generated RAG2(-/-)gamma c(-/-) mice in which we replaced the gene encoding mouse TPO by its human homolog. Homozygous humanization of TPO led to increased levels of human engraftment in the bone marrow of the hosts, and multilineage differentiation of hematopoietic cells was improved, with an increased ratio of myelomonocytic verus lymphoid lineages. Moreover, maintenance of human stem and progenitor cells was improved, as demonstrated by serial transplantation. Therefore, RAG2(-/-)gamma c(-/-) TPO-humanized mice represent a useful model to study human hematopoiesis in vivo.

引用

页码：2378 / 2383

页数：6

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