Pluripotent Cell Studies
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What are stem cells?
Stem cells are defined as the cells that have the abilities of differentation and self-renewal.
Differentiation is the event that one cell type becomes another ones.
The differentiation ability could be lost via cell division,
but the stem cells precisely transmit these abilities to at least one of the daughter cell to maintain a population, that is designated as self-renewal.
In development of mammal or that adult stage, there are various stem cells to hold a ability of various differentiation. But these are classified in embryonic stem cells and adult stem cells by the appearance time.
*Photo : a phase contrast microscope image of embryonic stem cells (ES cells) of mouse
幹細胞（stem cell）は、自己複製（self-renewal）する能力と分化（differentiation）する能力を兼ね備えた細胞として定義されます。
ここでいう自己複製とは、自己と同じ能力を有する幹細胞を細胞分裂を経て娘細胞として生み出すことを意味し、分化とは自己とは異なる種類の細胞になることを意味します。
哺乳動物の発生過程、あるいは成体内には、異なる分化能を持つ様々な幹細胞が存在しますが、これらはその出現時期により胚性幹細胞、胎児性幹細胞、成体幹細胞に分類されます。
*写真 マウスの胚性幹細胞(ES細胞)の位相差顕微鏡像
What are pluripotent Cells？
Totipotency is defined as an ability of a cell to generate a whole organism in cell autonomous manner, which should include an ability to generate all cell types.
To avoid the confusion in scientific as well as public arguments, the word pluripotency is carefully defined with clear distinction to totipotency.
Traditionally, pluripotency is sometimes defined as an ability to generate all cell types except TE because the analyses of chimeric embryos produced by injection of ICM cells and ES cells into 8 cell embryos or blastocycts showed their extinction from TE lineage.
However, it was revealed that these pluripotent cells still possess an ability to differentiate into proper TE lineage, so this distinction hallmark became obscure.
Therefore, in our labo., pluripotency is defined as an ability to generate all cell types including TE without selforganizing ability to generate a whole organism.
Similar opinion on the definitions of these terms are proposed by Solter (2006).
*Photo : Trophectoderm which differentiated from mouse embryonic stem cells (Immunostaining image) Red : PI Green : P-cadherin
また、幹細胞が持つ分化能は、多能性（pluripotency:多数の種類の細胞に分化する能力）、複能性（multipotent:少数の種類の細胞に分化する能力）、単能性（unipotent:単一の細胞に分化する能力）などに分類されます。
例えば、発生初期に出現するhemangioblastは全ての種類の血液細胞と血管細胞に分化できる胎児性複能性幹細胞といえますし、成体の精巣に存在する精原細胞は精子にのみ分化できる成体単能性幹細胞です。
*写真 マウス胚性幹細胞から分化した栄養外胚葉の免疫染色像 （赤：PI 緑：P-cadherin）
マウス胚性幹細胞は胚体組織及び胚体外組織(原始内胚葉、栄養外胚葉)に分化出来る多能性を持った細胞である。
Our research activities
Embryonic stem (ES) cells are the best known example of a type of stem cell possessing these properties of pluripotency and self-renewal. In our lab,
we use ES cells as a model system for studying the molecular mechanisms that determine and enable the mysterious properties of pluripotent cells.
In previous work, we identified a peptide hormone that works to maintain the ability of ES cells to self-renew and developed an ES culture medium using fully characterized components.
These developments were made in parallel with studies aimed at resolving the functions of genes involved in the maintenance of stem cells in an undifferentiated state and the induction of differentiation.
We have also identified a transcriptional factor that directs differentiation into placenta and yolk sac.
Given their ability to generate all of the body's cell types, ES cells have come to stand as a symbol for the emerging fields of cell replacement therapy and regenerative medicine,
but they also represent an ideal system for the study of many of the processes of early mammalian embryonic development.
The study of the basic biology of stem cells may one day bear fruit in the development of culture methods suitable for ES cells intended for clinical use or techniques for inducing differentiated cells to revert to a pluripotent state,
while at the same time providing fundamental new insights into the differentiation of extra-embryonic tissues in the earliest phases of mammalian development.
*Photo : Distribution of Cdx2 (green) and Oct3/4 (red) in blastocyst. Cdx2 localizes to trophectodermal regions, Oct3/4 to the inner cell mass.
我々はこのような幹細胞の基本的性質としての自己複製能と分化能を規定する分子機構を、
幹細胞の代表ともいえる胚性幹細胞（embryonic stem cell:ES細胞）を用いて研究しています。
ES細胞は着床前の初期胚に存在する多能性幹細胞に由来し、培養条件下で活発に自己複製を続け、条件の変化により分化するので、
このような研究の格好の材料です。
しかし、ES細胞が研究対象としてすばらしい点は、他にもまだまだあります。
ES細胞は胚への移植により全ての種類の細胞に分化することが保証できる多能性幹細胞で、
この能力は受精卵が持つ全能性（totipotency:単独で個体に発生する能力）と共通の分子基盤により制御されていると考えられますので、
その究明は、古典的な生命の神秘への挑戦でもあります。
また、ES細胞はうまく取り扱えば初期の発生過程を極めて忠実に模倣しつつ分化しますので、従来解析が困難で研究が遅れていた、
子宮内で起こる哺乳動物の初期発生過程のモデル系としても有用です。
さらには、現在ではヒトES細胞の再生医療への応用が期待されていますが、その基盤技術としての安全なES細胞増殖法の開発にもつながります。
このような、欲張った目標設定の中で、我々は研究を進めています。
*写真 マウス胚盤胞、免疫染色像 （赤：Oct3 緑：Cdx2）