Induction of hematopoietic stem/progenitor cells and functional blood cells from human ES/iPS cells

• Project/Area Number: 22790979
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: NIWA Akira 京都大学, iPS細胞研究所, 特定研究員 (20546999)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 造血発生 / 中胚葉分化 / 無血清培養 / 再生医学 / ES/iPS細胞 / ヒトES/iPS細胞 / 造血細胞分化 / ヒトES細胞 / ヒトiPS細胞 / 造血分化 / 造血幹細胞

Research Abstract

Elucidating the in vitro differentiation of human embryonic stem(ES) and induced pluripotent stem(iPS) cells is important for understanding both normal and pathological hematopoietic development invivo. For this purpose, a robust and simple hematopoietic differentiation system that can faithfullytrace in vivo hematopoiesis is necessary. In this study, we established a novel serum-free monolayerculture that can trace the in vivo hematopoietic pathway from ES/iPS cells to functional definitiveblood cells via mesodermal progenitors. Stepwise tuning of exogenous cytokine cocktails induced thehematopoietic mesodermal progenitors via primitive streak cells. These progenitors were thendifferentiated into various cell lineages depending on the hematopoietic cytokines present. Moreover, single cell deposition assay revealed that common bipotential hemoangiogenic progenitors wereinduced in our culture. Our system provides a new, robust, and simple method for investigating themechanisms of mesodermal and hematopoietic differentiation.

Research Products

• [Journal Article] Induced pluripotent stem cells from CINCAsyndrome patients as a model for dissecting somatic mosaicism and drugdiscovery (2012)
  • Author(s): Tanaka T, Takahashi K, Yamane M, Tomida S, Nakamura S, Oshima K, Niwa A, Nishikomori R, Kambe N, Hara H, Mitsuyama M, Morone N, Heuser JE, Yamamoto T, Watanabe A, Sato-Otsubo A, Ozawa S, AsakaI, Heike T, Yamanaka S, Nakahata T, and Saito MK
  • Journal Title: Blood
  • Peer Reviewed
• [Journal Article] A novel serum-free monolayer culture for orderly hematopoietic differentiation of human pluripotentcells via mesodermal progenitors (2011)
  • Author(s): Niwa A, Heike T, Umeda K, Oshima K, KatoI, Sakai H, Suemori H, Nakahata T, Saito MK
  • Journal Title: PLoS One Volume: 6(7)
  • Peer Reviewed
• [Journal Article] Neutrophil differentiation from human-induced pluripotent stem cells (2011)
  • Author(s): Morishima T, Watanabe K, Niwa A, Fujino H, Matsubara H, Adachi S, Suemori H, Nakahata T, Heike T
  • Journal Title: J Cell Physiol Volume: 226(5) Pages: 1283-91
  • Peer Reviewed
• [Journal Article] A novel serum-free monolayer culture for orderly hematopoietic differentiation of human pluripotent cells via mesodermal progenitors (2011)
  • Author(s): Niwa A, Heike T, Umeda K, et al.
  • Journal Title: PloS One Volume: 6 Issue: 7 Pages: e22261-e22261
  • DOI: 10.1371/journal.pone.0022261
  • NAID: 120003324603
  • Peer Reviewed
• [Presentation] ヒト多能性幹細胞由来造血支持細胞を用いた、二次元無血清条件における造血分化能の定量的評価の試み (2011)
  • Author(s): 丹羽明
  • Organizer: 第10回日本再生医療学会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-10
• [Presentation] ヒト多能性幹細胞由来造血支持細胞を用いた、二次元無血清条件における造血分化能の定量的評価の試み (2011)
  • Author(s): 丹羽明, 平家俊男, 梅田雄嗣, 大嶋宏一, 加藤格, 末盛博文, 中畑龍俊, 斎藤潤
  • Organizer: 日本再生医療学会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-09
• [Presentation] iPS細胞を用いた先天性造血不全疾患の解析への取り組み (2011)
  • Author(s): 丹羽明
  • Organizer: 先天性造血不全シンポジウム
  • Place of Presentation: 浦安
  • Year and Date: 2011-02-05
• [Presentation] PRIMITIVE AND DEFINITIVE HEMATOPOIESIS OF HUMAN ES AND IPS CELLS IN SERUM-FREE MONOLAYER CULTURE CONDITION (2011)
  • Author(s): 丹羽明
  • Organizer: ISSCR 8^<th> Annual Meeting
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2011-02-05
• [Presentation] ヒト多能性幹細胞を用いた、二次元無血清培養による段階的造血分化誘導 (2010)
  • Author(s): 丹羽明, 平家俊男, 梅田雄嗣, 大嶋宏一, 加藤格, 末盛博文, 中畑龍俊, 斎藤潤
  • Organizer: 日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-11
• [Presentation] ヒト多能性幹細胞を用いた、二次元無血清培養による段階的造血分化誘導 (2010)
  • Author(s): 丹羽明
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-11
• [Presentation] ヒトES/iPS細胞を用いた、二次元無血清条件による造血幹前駆細胞および成熟血球誘導の試み (2010)
  • Author(s): 丹羽明
  • Organizer: 第33回日本造血細胞移植学会
  • Place of Presentation: 松山
  • Year and Date: 2010-10-11
• [Presentation] ヒトES/iPS細胞からのin vitro二次元無血清造血誘導における、分化過程の経時的解析 (2010)
  • Author(s): 丹羽明
  • Organizer: 第31回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2010-08-05
• [Presentation] ヒトES/iPS細胞からのin vitro二次元無血清造血誘導における分化過程の経時的解析 (2010)
  • Author(s): 丹羽明, 平家俊男, 梅田雄嗣, 大嶋宏一, 加藤格, 末盛博文, 中畑龍俊, 斎藤潤
  • Organizer: 炎症再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-09
• [Presentation] In Vitro Orderly Haematopoiesis From Human Pluripotent Cells Traced In a Novel Monolayer Serum-Free Culture (2010)
  • Author(s): Niwa A, Heike T, Umeda K, Oshima K, KatoI, Sakai H, Suemori H, Nakahata T and Saito M
  • Organizer: American Society of Hematology, 52st Annual Meeting
  • Place of Presentation: Orlando, Florida, USA
• [Presentation] Primitive and definitive hematopoiesis of human ES and iPS cells in serum-free monolayer culture condition (2010)
  • Author(s): Niwa A, Saito M1, Kato I, Oshima K, Heike T, Nakahata T
  • Organizer: ISSCR, Annual Meeting
  • Place of Presentation: SanFrancisco, USA
• [Book] 幹細胞の体外増幅法の現状と将来医学のあゆみ (2012)
  • Author(s): 丹羽明、中畑龍俊
  • Publisher: 医歯薬出版
• [Book] ES, iPS細胞からの機能的赤血球産生血液フロンティア (2009)
  • Author(s): 丹羽明
  • Publisher: 医薬ジャーナル社
• [Book] iPS細胞からの造血分化Annual Review血液 (2009)
  • Author(s): 丹羽明, 中畑龍俊
  • Publisher: 中外医学社
• [Book] 疾患由来iPS細胞の樹立分子細胞治療 (2009)
  • Author(s): 丹羽明, 中畑龍俊
  • Publisher: メテオMBC