Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis

被引：137

作者：

Ma, Feng ^{[1
,2
,3
]}

Ebihara, Yasuhiro ^{[1
]}

Umeda, Katsutsugu ^{[5
]}

Sakai, Hiromi ^{[4
,6
]}

Hanada, Sachiyo ^{[1
]}

Zhang, Hong ^{[4
,6
]}

Zaike, Yuji

Tsuchida, Eishun ^{[4
,6
]}

Nakahata, Tatsutoshi ^{[5
]}

Nakauchi, Hiromitsu ^{[2
,3
]}

Tsuji, Kohichiro ^{[1
]}

机构：

[1] Univ Tokyo, Adv Clin Res Ctr, Div Cellular Therapy, Tokyo 1088639, Japan

[2] Univ Tokyo, Lab Stem Cells Therapy, Ctr Med Expt, Inst Med Sci, Tokyo 1088639, Japan

[3] Univ Tokyo, Inst Med Sci, Res Hosp, Dept Pediat Hematol Oncol, Tokyo 1088639, Japan

[4] Univ Tokyo, Inst Med Sci, Res Hosp, Dept Lab Med, Tokyo 1088639, Japan

[5] Kyoto Univ, Grad Sch Med, Dept Pediat, Kyoto 6068507, Japan

[6] Waseda Univ, Inst Biomed Engn, Tokyo 1620041, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 35期

基金：

日本学术振兴会;

关键词：

development; erythropoiesis; hemoglobin; primitive hematopoiesis;

D O I：

10.1073/pnas.0802220105

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：

A critical issue for clinical utilization of human ES cells (hESCs) is whether they can generate terminally mature progenies with normal function. We recently developed a method for efficient production of hematopoietic progenitors from hESCs by coculture with murine fetal liver-derived stromal cells. Large numbers of hESCs-derived erythroid progenitors generated by the coculture enabled us to analyze the development of erythropoiesis at a clone level and investigate their function. The results showed that the globin expression in the erythroid cells in individual clones changed in a time-dependent manner. In particular, embryonic epsilon-globin-expressing erythroid cells from individual clones decreased, whereas adult-type beta-globin-expressing cells increased to approximate to 100% in all clones we examined, indicating that the cells undergo definitive hematopoiesis. Enucleated erythrocytes also appeared among the clonal progeny. A comparison analysis showed that hESC-derived erythroid cells took a similar differentiation pathway to human cord blood CD34(+) progenitor-derived cells when examined for the expression of glycophorin A, CD71 and CD81. Furthermore, these hESC-derived erythroid cells could function as oxygen carriers and had a sufficient glucose-6-phosphate dehydrogenase activity. The present study should provide an experimental model for exploring early development of human erythropoiesis and hemoglobin switching and may help in the discovery of drugs for hereditary diseases in erythrocyte development.

引用

页码：13087 / 13092

页数：6

共 22 条

[1] Definitive-like etythroid cells derived from human embryonic stem cells coexpress high levels of embryonic and fetal globins with little or no adult globin [J].

Chang, Kai-Hsin ;

Nelson, Angelique M. ;

Cao, Hua ;

Wang, Linlin ;

Nakamoto, Betty ;

Ware, Carol B. ;

Papayannopoulou, Thalia .

BLOOD, 2006, 108 (05) :1515-1523

[2] TOTIPOTENT HEMATOPOIETIC STEM-CELLS - NORMAL SELF-RENEWAL AND DIFFERENTIATION AFTER TRANSPLANTATION BETWEEN MOUSE FETUSES [J].

FLEISCHMAN, RA ;

CUSTER, RP ;

MINTZ, B .

CELL, 1982, 30 (02) :351-359

[3] Hematopoietic colony-forming cells derived from human embryonic stem cells [J].

Kaufman, DS ;

Hanson, ET ;

Lewis, RL ;

Auerbach, R ;

Thomson, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (19) :10716-10721

[4] CD81 (TAPA-1): A molecule involved in signal transduction and cell adhesion in the immune system [J].

Levy, S ;

Todd, SC ;

Maecker, HT .

ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :89-109

[5] Development of human lymphohematopoietic stem and progenitor cells defined by expression of CD34 and CD81 [J].

Ma, F ;

Wada, M ;

Yoshino, H ;

Ebihara, Y ;

Ishii, T ;

Manabe, A ;

Tanaka, R ;

Maekawa, T ;

Ito, M ;

Mugishima, H ;

Asano, S ;

Nakahata, T ;

Tsuji, K .

BLOOD, 2001, 97 (12) :3755-3762

[6] Direct development of functionally mature tryptase/chymase double-positive connective tissue-type mast cells from primate embryonic stem cells [J].

Ma, Feng ;

Kambe, Naotomo ;

Wang, Dan ;

Shinoda, Gen ;

Fujino, Hisanori ;

Umeda, Katsutsugu ;

Fujisawa, Akihiro ;

Ma, Lina ;

Suemori, Hirofumi ;

Nakatsuji, Norio ;

Miyachi, Yoshiki ;

Torii, Ryuzo ;

Tsuji, Kohichiro ;

Heike, Toshio ;

Nakahataa, Tatsutoshi .

STEM CELLS, 2008, 26 (03) :706-714

[7] Novel method for efficient production of multipotential hematopoietic progenitors from human embryonic stem cells [J].

Ma, Feng ;

Wang, Dan ;

Hanada, Sachiyo ;

Ebihara, Yasuhiro ;

Kawasaki, Hirohide ;

Zaike, Yuji ;

Heike, Toshio ;

Nakahata, Tatsutoshi ;

Tsuji, Kohichiro .

INTERNATIONAL JOURNAL OF HEMATOLOGY, 2007, 85 (05) :371-379

[8] Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleures by aorta-gonad-mesonephros region-derived stromal cells [J].

Matsuoka, S ;

Tsuji, K ;

Hisakawa, H ;

Xu, MJ ;

Ebihara, Y ;

Ishii, T ;

Sugiyama, D ;

Manabe, A ;

Tanaka, R ;

Ikeda, Y ;

Asano, S ;

Nakahata, T .

BLOOD, 2001, 98 (01) :6-12

[9] HEMATOPOIETIC COLONY-FORMING CELLS IN UMBILICAL-CORD BLOOD WITH EXTENSIVE CAPABILITY TO GENERATE MONOPOTENTIAL AND MULTIPOTENTIAL HEMATOPOIETIC PROGENITORS [J].

NAKAHATA, T ;

OGAWA, M .

JOURNAL OF CLINICAL INVESTIGATION, 1982, 70 (06) :1324-1328

[10] Hematopoiesis and stem cells:: plasticity versus developmental heterogeneity [J].

Orkin, SH ;

Zon, LI .

NATURE IMMUNOLOGY, 2002, 3 (04) :323-328

← 1 2 3 →