JP4521572B2 - 細胞の評価方法、細胞測定用システム、及び細胞測定用プログラム - Google Patents
細胞の評価方法、細胞測定用システム、及び細胞測定用プログラム Download PDFInfo
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Description
2 蛍光検出装置
2a 蛍光顕微鏡
3 撮像装置
3a ビデオカメラ
4 画像解析装置
4a パーソナルコンピュータ
5 出力装置
5a モニター
6 入力装置
6a キーボード
6b マウス
7 補助記憶装置
8 プログラム記憶媒体
41 制御部
42 記憶部
以下、本実施例に係る細胞測定用システムについて説明する。
[実験]
1.GFP−ヒストンH1発現HeLa細胞の構築
染色体はDNAと染色体タンパク質から構成されるが、本実施例で、主要な染色体タンパク質であるヒストンH1を蛍光タンパク質であるGFPと融合させることで生細胞における染色体の可視化をほぼ全ての組織で恒常的に発現している(Meergans et al.,1997)ヒストンH1.2を選択した。
GFP−ヒストンH1発現HeLa細胞について、上述の細胞測定用システムの内、図4におけるステップS3のステージ判定に図7に示すフローチャートを採用したシステムにより、タイムラプスモードにて測定を行った。図8は、図4のステップS8における平均値をタイムラプス解析結果として示す。図8(a)は対照のタイムラプス解析結果、図8(b)は中期阻害剤ノコダゾールを15ng/mlの最終濃度で添加した対象のタイムラプス解析結果、図8(c)は中期阻害剤ノコダゾールを150ng/mlの最終濃度で添加した対象のタイムラプス解析結果を示す。尚、図8(a)〜(c)において、横軸は時間を表し、P1は間期、P2は前期、P3は前中期、P4は中期、P5は後期、P6は終期を表す。図8(c)より、中期阻害剤ノコダゾールを150ng/mlの最終濃度で添加すると、前中期で細胞分裂が停止した状態であることがわかる。また図8(b)より、中期阻害剤ノコダゾールを15ng/mlの最終濃度で添加すると、前中期が遅延したことがわかる。この様に細胞活性の低下を細胞分裂期の特定のステージにある時間の変化として捉えることができ、従来の固定細胞による細胞活性評価法では検出できなかった様な低濃度における阻害物質の細胞活性への影響を評価することが可能になったことを示している。
Claims (9)
- (a)特定の生細胞内における染色体の状態を反映する画像を所定時間間隔毎取得する工程、及び、
(b)前記画像に基づいて、染色体の状態に対応するパラメータを算出し、前記算出の結果に基づいて前記特定の生細胞の細胞周期における所定時間間隔毎のステージを判定する工程、を有し、
前記パラメータとして、染色体の円形度、染色体の丸み度、染色体の長軸と短軸の長さの比、染色体の真円度、染色体のフェレ直径、染色体とこれに近接する染色体との重心間の距離、染色体の長軸とこれに近接する染色体の長軸との角度、またはこれらの複数を含む、細胞の評価方法。 - (c)前記工程(a)の前に、前記細胞内で染色体タンパク質と蛍光を発するタンパク質との融合体を発現させる工程、を有し、
前記工程(a)において、前記画像は前記細胞が発する蛍光に由来する蛍光画像である、請求項1に記載の細胞の評価方法。 - (d)前記工程(b)の判定の結果に基づいて、前記細胞の活性度を評価する工程、をさらに有する請求項1又は2に記載の細胞の評価方法。
- 前記工程(a)において、試料中の複数の細胞に対応する画像を取得し、
前記工程(b)において、複数の細胞についてそれぞれ前記ステージを判定し、
前記工程(d)において、各ステージにある細胞数の割合を算出し、前記算出の結果に基づいて細胞の活性度を評価する、請求項3に記載の細胞の評価方法。 - 前記工程(d)において、特定の細胞の時間変化に対するステージ変化の情報に基づいて細胞の活性度を評価する、請求項3に記載の細胞の評価方法。
- 特定の生細胞内の染色体の状態を反映する蛍光を検出する蛍光検出装置と、前記蛍光検出装置で検出した蛍光に由来する蛍光画像を所定時間間隔取得する撮像装置と、前記撮像装置で取得した蛍光画像に基づいて染色体の状態に対応するパラメータを算出し、前記算出の結果に基づいて前記特定の生細胞の細胞周期における所定時間間隔毎のステージを判定する画像解析装置とを備え、
前記パラメータとして、染色体の円形度、染色体の丸み度、染色体の長軸と短軸の長さの比、染色体の真円度、染色体のフェレ直径、染色体とこれに近接する染色体との重心間の距離、染色体の長軸とこれに近接する染色体の長軸との角度、またはこれらの複数を含む、細胞測定用システム。 - 前記蛍光検出装置は、試料中の複数の細胞に由来する蛍光を同時に検出し、
前記撮像装置は、試料中の複数の細胞が発する蛍光の情報を含む蛍光画像を取得し、
前記画像解析装置は、前記撮像装置により取得した蛍光画像から、各細胞に対応する蛍光画像を切出し、各細胞について細胞周期におけるステージを判定する、請求項6に記載の細胞測定用システム。 - 特定の生細胞内の染色体の状態を反映する蛍光を検出し、前記蛍光を蛍光画像として所定時間間隔取得し、前記蛍光画像に基づいて染色体の状態に対応するパラメータを算出し、前記算出の結果に基づいて前記特定の生細胞の細胞周期における所定時間間隔毎のステージを判定する手順をコンピュータに実行させ、
前記パラメータとして、染色体の円形度、染色体の丸み度、染色体の長軸と短軸の長さの比、染色体の真円度、染色体のフェレ直径、染色体とこれに近接する染色体との重心間の距離、染色体の長軸とこれに近接する染色体の長軸との角度、またはこれらの複数を含む、細胞測定用プログラム。 - 特定の生細胞内内の染色体の状態を反映する蛍光を検出し、前記蛍光を蛍光画像として所定時間間隔取得し、前記蛍光画像に基づいて染色体の状態に対応するパラメータを算出し、前記算出の結果に基づいて前記特定の生細胞の細胞周期における所定時間間隔毎のステージを判定する手順をコンピュータに実行させ、
前記パラメータとして、染色体の円形度、染色体の丸み度、染色体の長軸と短軸の長さの比、染色体の真円度、染色体のフェレ直径、染色体とこれに近接する染色体との重心間の距離、染色体の長軸とこれに近接する染色体の長軸との角度、またはこれらの複数を含む、細胞測定用プログラムを記録したコンピュータ読取可能な記録媒体。
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JP2013230145A (ja) * | 2012-04-30 | 2013-11-14 | Masahiko Sato | 細胞集団の状態を評価するための方法、候補化合物の発癌性を評価するための方法、潜在的な抗癌化合物の抗癌活性を評価するための方法及び治療用細胞集団の品質を評価するための方法 |
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