Were STAP cells derived from ES cells?

If STAP cells were fabricated maliciously, who can make 129X1/SvJmsSlc♀×B6(C57BL/6TgN, acro/act-EGFP Chr3, ♂) ES cells?
Were STAP cells derived from ES cells?

Were STAP cells derived from ES cells? - what happened in Japan

I cannot winnow whether these embryonic stem cells which Dr.Wakayama and Dr.Ohta submitted to analysts are really established in 2005 by different type of gene from those described in paper or other cells relation to (or from) "cells as STAP", so I cannot confirm respected researchers opinion , doi:10.1038/nature15366 .
Original STAP cell ; LETTER ( doi:10.1038/nature12969 ), Article ( doi:10.1038/nature12968 ).

FES1,FES2 (ES cell)≠"Cell as FES1 (ES cell)","Cell as FES2 (ES cell)"

Written in 2005 , FES1,FES2 (ES cell):129/Sv-ter♀×B6(C57BL/6TgN(acro/act-EGFP)OsbC3-N01-Fj002♂)
Analysis result In 2014 , "Cell as FES1 (ES cell)","Cell as FES2 (ES cell)":129X1/SvJmsSlc ♀×B6(C57BL/6NCrSlc)♂(C57BL/6TgN♂, Acr/cag-GFP at chromosome 3)

ntESG1, ntESG2≠"Cell as ntESG1", "Cell as ntESG2"

Written in 2005 ntESG1,ntESG2 :129/Sv-ter♀×B6(C57BL/6TgN(acro/act-EGFP)OsbC3-N01-Fj002♂)
Analysis result In 2014 "Cell as ntESG1", "Cell as ntESG2":B6(C57BL/6NCrSlc)(Acr/cag-GFP) ×129+Ter/SvJcl.♂

Are these Dr.Wakayama and Dr.Ohta's mistakes in 2005?

Cells as FES1, as FES2, as ntESG1, as ntESG2 which submitted by Dr.Ohta have not official records (1, 2). The Wakayama lab in Yamanashi univ. has not been closed so these cells have not been sealed for the perpetuation of evidence. It is very important Riken announced FLS3 and FLS4 with "B6129" at June 16, 2014 , since ntESG1 and ntESG2 are "B6129". Until December 25,2014, everybody thought that ntESG1 and ntESG2 were 129B6. It is necessary to know mtDNA of these cells and tissues especially too big placenta.

大田氏はこの岡部マウスと市販の白マウスを掛け合わせて受精卵を取り,その受精卵からES細胞を作った。だが研究には使わず,そのまま保存していた。...大田氏は2010年3月に他大学に転出し,その際にES細胞は「すべて持ち出したつもりだが,同じ株がCDBにあったのなら,置き忘れたかもしれない」と話している。 幻想の細胞 判明した正体, 詫摩雅子,古田彩, 2015
論文に書かれていたのはクレアの129+Terだったが、遠藤氏はSTAP論文のNGSデータから,FLSの親マウスは129X1だと予測した。...大田氏によると,このES細胞2株は,核移植ES細胞を作ったのと同じころ、たまたま作ったES細胞だという。結局研究に使うこともなく,2010年3月に他大学に転出する際にすべて持って出たと思っていた。大田氏の記憶では母マウスはクレア社の茶色い129+Terマウスだったが,実際には129X1の白マウスだった。 P.53, 日経サイエンス2015年3月号 P.53, Nikkei Science March, 2015

Is STAP cell trisomy8 come down to ES cell?

On June 11,2014 Nikkei Science reported that STAP cell was ES cell because ratio of STAP cell mRNA SNPs online-data is trisomy8. On Sep 21,2014, Dr.Takaho A Endo published same analysis result.
But I think We can't measure ratio of chromosome by mRNA SNP ratio because we cannot count Intron SNPs by mRNA data and Intron has SNPs more than Exon.
mRNA SNP ratio can't show ratio of chromosome so I cannot say STAP cell is trisomy8 and ES cell

Why do they not analyze all cells?

Why do they not analyze all cells which moved to Yamanashi University (listed in Material Transfer Agreement document at April 1, 2014).
There are some kind of the cells which they do not analyze. STAP stem cells FLB that established at Jan 31 to Feb 3, 2012 and control ES cell (129B6F1GFP-1) and control TS cell (129B6F1 TS-1) established with Callus TS-1 (FI stem cell CTS) at May 25,2012.
STAP-cell MTA, RIKEN Yamanashi Univ

Why do 129 cag-GFP mouse and FES1 ES cell show the same pattern of B6/B6?

Why do 129 cag-GFP mice which Dr. Wakayama made in 1999 by backcrossing and FES1 ES cell made from commercially available 129X1 mice show the same pattern of B6/B6? Nikkei science March 2015 pp.52 said twenty years ago, 129X1 mouse mated with B6 mouse in the Jackson Laboratory, so commercially available 129X1 has B6/B6 segment. Is it true?
Oct 25, 2015 I find PM Petkov's Article (2004) (doi: 10.1101) that 129X1 would be polluted by C57BL/6J and BALB/cJ. But I can not find reasons why Chromosomes 2, 4, 8, 9, 10, 11, 12, 15, 16, 17, and X are contaminated by B6.
129X1 is polluted in B6(C57BL/6J). FES, FLS, CTS is polluted in B6(C57BL/6) more than 129X1. It is necessary to check whether FES, FLS, CTS are polluted in C57BL/6N (FES is 129X1SLC×B6NSLC ) and compare mtDNA of 129cag-GFP mouse with mtDNA of commercial 129X1. If FES is ntES , most chimera mice of FES would be male and would have big Placentas.

As a second example, we know that another strain of this group, 129X1/SvJ, was contaminated with unknown genetic material around 1987 (Simpson et al. 1997). An analysis with our SNP marker set revealed that the strain has contributions by C57BL/6J on Chromosomes 5, 7, 14, 18, and 19, and by BALB/cJ on Chromosomes 7, 8, 10, 18, 19, and X, suggesting an F1 hybrid between these strains as the most possible contaminant. An Efficient SNP System for Mouse Genome Scanning and Elucidating Strain Relationships, Petko M. Petkov, Michael V. Wiles et al. (2004) doi: 10.1101
この時(1976年から1984年にかけて)、J亜系にだけ、突然変異が入り、Nnt(nicotinamidenucleotide transhydrogenase)遺伝子のエキソン7から14が欠損してしまいました。C57BL/6Jマウス、最大の特徴といってもいいと思いますよ、これ。 …”しかしながら”、Nnt自体はミトコンドリアでの酸化ストレスに関わっているので、その辺*7を研究してる方は、当然、C57BL/6Jは問題があることになります。…1.同じ実験系で意図なく、NとJを混ぜて使わない(大前提)…3.論文で「C57BL/6」とJなのかNなのかわからない書き方してる時は、とりあえず眉間にシワよせてみる となります。うん。じゃぁ、C57BL/6マウスを使えばいいのか?, 動物学特論, May 02, 2014

Dr.Takaho A Endo said probably SLC 129X1's mitochondrial DNA would be B6 because 129 was polluted by B6 in the Jackson laboratory long time ago, so @kasukawa can not find difference between mtDNA and DNA.
Mitochondria of C57BL/6J is different from 129S1/SvlmJ in the mtDNA sequence of the AKR/J strain (AB042432) Dissecting the effects of mtDNA variations on complex traits using mouse conplastic strains, Xinhua Yu1, Saleh M. Ibrahim, (2009) doi: 10.1101/. However, I was not able to discover documents about which type of gene were 129X1SLC polluted with. If mitochondrial DNA of 129X1SLC is B6 (C57BL), It should be already reported a long time ago. (about 129/SvJ)

129 cag-GFP mouse and STAP cell
doi:10.1038/nature15366 Extended Data Figure 1

129X1マウスにはゲノムの所々にB6の黒マウスの配列が紛れ込んでおり、そのパターンがアクロシンプロモーターのある STAP細胞やFI幹細胞とよく似ていたからだ。129X1マウスのルーツを遡って調べたところ、20年以上前に、このマウス集団を 飼っていた米ジャクソン研究所でB6マウスが紛れ込む事故があったことが判明した。ならばこれは、129X1マウスに共通に観られる 特徴と考えていい。 P.53, 日経サイエンス2015年3月号 P.53, Nikkei Science March, 2015
In a series of strain name changes, strain 129/SvJ (Stock No. 000691) became 129X1/SvJ (Festing et al., 1999). The name change reflects a genetic contamination that occurred early in its history (Simpson et al., 1997; Threadgill et al., 1997). 129X1/SvJ genetically contaminated. What does that really mean?, The Jackson Laboratory, Jax Notes, Feb 1, 2001
However, genomic regions from strains other than C3HeB/FeJ and C57BL/6 were introduced into 129/SvJ and 129/Sv-+tyr +p.
Ter during their derivation since the non-129 genomic regions, including the segment on Chr 16, do not consistently match with these strains other than around the tyrosinase and pink-eyed dilute loci on Chr 7.
We also tested numerous strains carrying kit w and Mgf st alleles as sources of contamination, but were unable to identify the origin of genetic contamination.
Therefore, the 129/SvJ substrain should more appropriately be considered a re-combinant congenic strain, possibly named 129cX/Sv, between a 129/Sv background strain and an unknown donor strain(s), X.
Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain , David W. Threadgill, Delia Yee, Argabin Matin, Joseph H. Nadeau, Terry Magnuson,June 1997
意訳です:しかし、C3HeB/ FEJとC57BL/6以外の系統からのゲノム領域が、129/ SVJおよび129/ SV-+tyr + Pへと導入されました。
染色体第16番セグメントを含む非129ゲノム領域からのそれら派生の間のTerは、Chr 7のチロシナーゼ、およびピンク 見られた薄めの場所のまわりを除いたそれらの系統と一貫してマッチしていない。
また、汚染源としてkit wとMGF対立遺伝子を持つ多数の系統をテストしたが、遺伝子汚染の起源を特定することができませんでした。
したがって、129/ SVJの亜系は129cX/Svという名前で、129/ Svバックグラウンド系統と未知のドナー系統(系統達)"X"の 組換えコンジェニック系統としてより適切にみなされるべき。





STAP cell is ntES or ES-cell

1999

戻し交配で129X1マウスをつくる

Dr.Wakayama made B6:CAG-GFP and 129 into 129/sv CAG-GFP by backcrossing . (Dr.Wakayama June 16, 2014 . The Mainichi 【会見資料】STAP細胞:「あることを示す証拠はない」若山教授 )

This mouse strain was generated by a series of backcrosses of B6 CAG-GFP mice with 129X1/Sv. SNP analysis of the whole genome of a 129 CAG-GFP mouse revealed that the genetic background of the 129 CAG-GFP mice currently maintained in the Wakayama university lab, did not become completely homogeneous to the 129 genetic background. P.9, Report on STAP Cell Research Paper Investigation , Research Publication Investigative Committee, Dec 25,2014.
129CAG-GFPマウスは129X1/Svとの戻し交配よりB6CAG-GFPより 遺伝的背景を129 に置き換えたものであるが、現在、山梨大学若山研で維持されている129 CAG-GFPマウスの全ゲノムのSNP解析から、 129 CAG-GFPマウスの遺伝的背景が十分に均一化されていないことが判明した。 P.9, 研究論文に関する調査報告書 , 2014/12/25

Time series of STAP cell case

2003

岡部マウス

These features are identical to those of the Acr-GFP/CAG-GFP mice which the Wakayama CDB lab had obtained from Prof.Masaru Okabe’s lab at Osaka University in 2003. ※P.5,2-3-1-1(b) 1), Report on STAP Cell Research Paper Investigation ,Research Publication Investigative Committee, Dec 25,2014.
これらの特徴は、2003年にCDB若山研が大阪大学岡部研より導入したAcr-GFP/CAG-GFPマウスの特徴と完全に一致する。 P.5 ,研究論文に関する調査報告書 2-3-1-1(b) 1),2014/12/25

→B6:C57BL/6-TgN(acro/act-EGFP) OsbC3-N01-FJ002 (Background strain:C57BL/6Cr Slc(C57BL/6NCrSlc))Okabe, Masaru (Osaka university)
B6:C57BL/ 6TgN(acro/act-EGFP) OsbC3-N01-FJ002
glimmer body and tip of spermatozoa by exciting wavelength 480 nm

「C57BL/6CrSlc ⇒ C57BL/6NCrSlc 2010 年 1 月納品分より系統表記変更」 ”C57BL/6CrSlc マウス系統名変更のお知らせ”日本エスエルシー株式会社,2009 年 11 月 1 日

2005

大田ES細胞

In 2005, Dr.Wakayama and Dr.Ohta established FES1,FES2,ntESG1,ntESG2.

However, these cell lines had co-insertions of two GFP transgenes, sperm-specific acrosin-promoter-gfp and ubiquitously expressed cag-gfp (hereafter designated Acr/cag-gfp) at chromosome 3, which originated from an Acr/cag-GFP B6 mouse strain not described in the STAP papers. These STAP cell lines were then compared with four ES cell lines—FES1, FES2, and two nuclear transfer ES lines (ntESG1 and ntESG2) (ref. 9)—established from crossing the Acr/cag-GFP mouse strain with 129 mice in the Wakayama laboratory in 2005 (Extended Data Fig. 1a and Extended Data Table 1).” doi:10.1038/nature15366 (Sep,2015)

2006

Aug 25,2006 Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors, Kazutoshi Takahashi, Shinya Yamanaka

2007

Nov 30, 2007 Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors, Kazutoshi Takahashi1, Shinya Yamanaka

2009

Oct 8 2009, The Muse-cell report was submitted.

Aug 2009, Charles A. Vacanti and Dr.Obokata submitted report about natural Spore-like stem cells.

「STAP細胞」の原形となる論文が完成したのは、撮影から4カ月後の09年8月。ところが10年春、論文は米科学誌に 採用されなかった。「ほぼアクセプト(採用)とのコメントをもらってみんなで喜んだが、1、2週間後に却下の返事が来て 声を失った。その後の2〜3年は彼女は本当につらかっただろう」 」 STAP細胞:くじけなかった小保方さん 研究に壁で涙も” 毎日新聞 2014年02月01日

2010

March 29 2010, The Muse-cell report was published.

あるときトリプシンという酵素が入った溶液を培養液と取り違え、そのまま一晩置いてしまった。「翌日、培養液が黄色であるのを見て、トリプシンによる消化で細胞を駄目にしてしまったとがく然としたが、顕微鏡でよく観察してみると、浮いている細胞の中に生きているものがいることを発見した」と出澤教授。このことが、今回の成果に至る原点となった。 がん化や倫理問題を回避した、第三の多能性幹細胞を発見!西村尚子(サイエンスライター), naturejapan, 2010年6月10日

Apr 2010, Charles A. Vacanti and Dr.Obokata report about natural Spore-like stem cells was rejected.STAP細胞:くじけなかった小保方さん 研究に壁で涙も” 毎日新聞 2014年02月01日

2010年大田ES細胞は京都大学へ移動した

ES細胞FES1は2005年に当時のCDB若山研メンバーによって樹立されたが、その後、研究に使わず、2010年3月 (CDB若山研でSTAP研究が始まる前)に転出した時にES細胞FES1の凍結保存試料を全部持ち出してCDB若山研 には残さなかったとされている。P.14,研究論文に関する調査報告書,2014/12/25
FES1 ES cells which had been established by a member of the Wakayama CDB lab in 2005, were not used for research in the Wakayama CDB lab. When this lab member left in March 2010, the member took all the frozen FES1 cell samples, leaving none in the Wakayama CDB lab.P.14,Report on STAP Cell Research Paper Investigation,Research Publication Investigative Committee,Dec 25,2014)

Oct 2010, Obokata submitted a thesis. Someone confused rough draft with the thesis.

2011

May 4, 2011

iPS cells were generated exclusively from Muse cells but not from non-Muse cells. Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts, Shohei Wakaoa, Yasumasa Kuroda, Mari Dezawaa et al. doi: 10.1073/pnas.1100816108

東北大と京大のチームが、さまざまな細胞になる能力を持つiPS細胞の元になる細胞を突き止め、今週号の米科学アカデミー紀要(電子版)に発表した。この細胞は、同じチームが2010年発表した「Muse(ミューズ)細胞」と呼ばれる神経や筋肉などの細胞になる多能性幹細胞。…共著者の藤吉好則・京大教授は「(謎だった)遺伝子の役割を提示できた」と強調する。今回、ミューズ細胞から作ったiPS細胞をマウスに移植したところ、腫瘍ができた。一方、ミューズ細胞は他の多能性幹細胞よりがんができにくい点が長所とされており、チームは今後、有効性の検証を進めていく方針だ。iPS細胞:「ミューズ」が元 東北大・京大チーム、多能性の起源解明に道, 野田武, 毎日新聞 2011年5月31日
共同研究者の藤吉好則・京都大大学院理学研究科教授は、「線維芽細胞以外での検証が必要だが、今回の成果からは多能性を備えていた細胞が、無限増殖能を獲得してiPS細胞が形成されている可能性が示唆される」と解説する。また、出沢教授は「がん化の危険のないMuse細胞で、再生医療の可能性を広げたい」と話した。iPS細胞の「元」発見 多能性備え、がん化せず, MSN産経ニュース, 2011年5月31日

March 15, 2011, Dr.Obokata took a doctor’s degree (Waseda Univ.,Engineering), began to go to Dr.Wakayama’s lab in RIKEN CDB.
Isolation of pluripotent adult stem cells discovered from tissues derived from all three germ layers the chief examiner:Masayuki Yamato, Charles A. Vacanti (authors of STAP)

2012

Jan ,2012 (iPS SCs) Survival of Human Induced Pluripotent Stem Cell–Derived Midbrain Dopaminergic Neurons in the Brain of a Primate Model of Parkinson's Disease Kikuchi, Tetsuhiro, Takahashi, Jun et al.

Oct 8,2012 Shinya Yamanaka wins Nobel Prize.

Dec 3, 2012

In a small but hopeful step for researchers working on therapies to treat Parkinson’s disease, a team in Japan has used stem cells harvested from bone marrow to restore function in monkeys with the debilitating condition. Stem cell transplant boosts function slightly in Parkinson's monkeys, By Eryn Brown

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques, Takuya Hayashi, Mari Dezawa et al.doi:10.1172/JCI62516

2013

2013 MUSE cell project NEDO P10004 project leader, Dr.Masayuki Yamato deputize.
MUSE細胞 プロジェクトリーダー代行東京女子医科大学教授大和雅之

Feb 22, 2013 The basic patent on Muse cells and the isolation method thereof has been granted. by NEDO

April 27, 2013

Epigenetic alterations were not seen in non-Muse cells and some of the major pluripotency markers were not expressed for the entire period of generation, suggesting that Muse cells that are already pluripotent selectively become iPS cells by acquiring tumorigenic proliferative activity, whereas the remaining cells make no contribution to the generation of iPS cells Intrinsic pluripotent stem cells, Muse cells, are a primary source of iPS cells in human fibroblasts, Mari Dezawa FASEB J. April 2013

December 20, 2013 STAP ARTICLE and LETTER Accepted.

2014

Jan

Jan 28 ,2014 pre-Press Release at RIKEN CDB.

――iPS細胞と比べ、染色体やDNAの損傷に違いはあるか。
「STAP細胞では染色体に異常を起こさず初期化できている」
――がん化する可能性は。
「大きな腫瘍(しゅよう)をつくる性質がない。がん化の可能性は低いのではないか」
…――再生医療への応用の可能性は。
「今回はマウスの赤ちゃんの細胞を使った報告なので、条件が限られている。iPS細胞との関連を議論するのは早すぎる段階だ。数十年後、100年後の人類への貢献を考えて研究を進めたい」 様々な組織へ、高い分化能力 STAP細胞 小保方晴子リーダー会見 ,朝日新聞,2014年1月30日

Dr.Sasai apologize to Dr Shinichi Yamanaka later for their picture misled the media to report passionately in chorus about iPS cell is low reprogramming efficiency.

Jan 29 ,2014 STAP ARTICLE and LETTER Published online. The media got wildly excited by her.

Feb

Feb 4 ,2014 indicate of electrophoresis by pubpeer.

Feb 7 ,2014 Dr.Shinichi Yamanaka bring a complaint to Tv program about iPS cell and STAP cell. iPS cell has improved considerably compared with what it was about cancer-prone and reprogramming efficiency.

Feb 10 ,2014 Dr.Masayuki Yamato said he and Charles A Vacanti conceive pluripotent stem cells are made by stimulation severally at the same time in 2010. He said iPS cell is cancer prone but STAP cell is non-cancer-prone.

「刺激で万能細胞が作れるというアイデアは、ハーバード大のチャールズ・バカンティ教授と私が2010年にそれぞれ独立に思いついたことだが、小保方さんのように一生懸命やる人がチームに加わらなかったら、今回の発見は数年単位で遅れていたと思う」…「iPSは腫瘍ができる課題が解消されていないが、STAPはできにくい。」 東京女子医大・大和雅之教授「10年以内に臨床研究」、慶応大・岡野栄之教授「慎重な検証が必要だ」,産経ニュース,2014年2月10日

Feb 13 ,2014 indicate by famous science misconduct blogger.

電気泳動
people1

Drs. Obokata and Sasai submitted an electronic file of the photos of the gels on which Figure 1i is based, lab notes, and a written explanation of the process and methods used to create the figure. The two were also interviewed separately
…With regard to the electrophoresed samples, the information provided by Dr. Obokata, including sample tube labels and the lab notes, indicated that lanes 1, 2, 4, and 5 in Figure 1i are consistent with the paper, and that the “Lymphocytes” label for lane 3 refers to CD45+/CD3+ T lymphocytes.
…It would appear that Dr. Obokata did not, at that time, sufficiently understand the prohibitions against the action that she had taken, nor did she appear to know Nature’s criteria for presenting such data in a way that would not call its authenticity into question.
Even though her direct intent may not have been to deliberately mislead other researchers or lead them to incorrect interpretations of the data, our conclusion is that she was aware of the danger.
It is evident that her purpose in creating the composite image was to articulate the T-cell receptor gene rearrangement band and that she did so without applying scientific consideration or procedures. We therefore conclude that this was an act of research misconduct corresponding to falsification. P.4,Report on STAP Cell Research Paper Investigation,March 31, 2014
標準DNA サイズマーカーの位置情報に基づいてレーン3 の写真の挿入位置を決定したとの説明があった。
…電気泳動されたサンプルについては、実験ノート類などの記載やサンプルチューブのラベルなど小保方氏から提供された各種の情報は、 Figure 1i のレーン1, 2,4, 5 は論文のとおりであること、論文で「Lymphocytes」とラベルされたレーン3はCD45+CD3+ T リンパ球で あることを示していた。
…当時の小保方氏には、このような行為が禁止されているという認識が十分になかった、また、このようなデータをその真正さを損なう ことなく提示する方法についてNature 誌が指定していることを認知していなかったともうかがえる点がある。研究者を錯覚させるだけでなく、 データの誤った解釈へ誘導することを、直接の目的として行ったものではないとしても、そのような危険性について認識しながらなされた 行為であると評価せざるを得ない。
P.4,研究論文の疑義に関する調査報告書,研究論文の疑義に関する調査委員会 (石井俊輔委員長),平成26年3月31日

Feb 20,2014 Several days before meeting at Feb 20,2014, Dr.Sasai listened from Dr.Obokata about the mistake of teratoma photographs.
テラトーマ
On Dec 26,2014, Dr.Isao Katsura Chair of Research Publication Investigative Committee said that Dr.Sasai rewrote stimulus to Hcl and did not write physical stimulus and ATP that she tried many times.

笹井氏は、2月20日の委員会のヒアリングの数日前に小保方氏から画像の取り違え等について知らされ、論文を訂正するための正しいデータを至急取り直すことを小保方氏に指示したと説明した。実際に、訂正のために提出されたテラトーマに関する画像の作成日の表示は2014年2月19日であった。笹井氏から、学位論文は投稿論文に使用できると認識していた、正しいと思われるデータが得られたことから、学位論文の画像が使用されていた件については委員会のヒアリングでは言及しなかったが、この点については深く反省しているとの説明を受けた。 P.7”研究論文の疑義に関する調査報告書”,研究論文の疑義に関する調査委員会,平成26年3月31日
Dr. Sasai was informed of the incorrect images by Dr. Obokata only a few days before the February 20 interviews with the investigative committee. He explained that he immediately instructed Dr. Obokata to prepare accurate image data so that the submitted paper could be corrected. The immunofluorescence images of teratoma that were submitted to replace the incorrect images were created on February 19. Both Dr. Sasai and Dr. Obokata expressed deep regret for not telling the investigative committee that material had been used from a doctoral thesis, explaining that they had assumed it was permissible to do so, and that they did not think an explanation was necessary because they had been able to produce the correct images for replacement. P.7, Report on STAP Cell Research Paper Investigation, Research Paper Investigative Committee, March 31,2014

Mar

Mar 5,2014 Protocol exchange

Mar 6,2014 Some researcher said STAP stem cell don't have TCR-rearrangement mean no evidence of T-cell became STAP 1 ,2 , 3 . They said STAP-cell may not exist.

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Mar 9,2014 All the authors agreed to a correction, submitted to Nature again.P.31(P.63)

Mar 9 ,2014 teratoma photographs indicate by famous science misconduct blogger, 11jigen
Mar 10,2014 The mass media reported about teratoma photographs .
テラトーマ

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Mar 10,2014 Dr.Wakayama wanted retracting. 「若山先生は『確信を持てなくなった』。さらにSTAP細胞の万能性を示す重要なテラトーマのデータが昔の写真の使い回しである事がわかって若山先生も目が覚めたのであろう。

Mar 11 ,2014 Dr.Takaho A Endo said STAP cells were ES-cells (analysis of CNV).

Mar 13, 2014 Dr.Obokata’s lab closed.

Mar 19, 2014 Shukan-Bunshun and Shukan Shincho created some scandal. Some of them had been comment on Dr.Endo's blog. They began to receive some violent criticism.

Mar 25 ,2014 NHK reported that Dr.Wakayama sent 129 mouse to Dr.Obokata, she returned 129B6F1 to him. (News 7 broadcasting program).

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Mar 27, Weekly magazine Jyosei-seven (SHOGAKUKAN Inc.) created scandal. Some of them had been comment on Dr.Endo's blog.

Apr

Apr 01 ,2014 Research Publication Investigative Committee adjudged her misconduct.

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Apr 09 ,2014 Dr.Obokata press conference.

Apr 10, 2014 Shukan-Bunshun and Shukan Shincho created some scandal. Some of them had been comment on Dr.Endo's blog.

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Apr 11 ,2014 Nature rejected Dr.Endo’s paper (STAP is ES cell). Nikkei Science March, 2015 P.48

Apr 16 ,2014 Dr.Sasai press conference, recommended inspection experiment stringently.

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May

May 10 ,2014 the authors corrected Letter Extended Data Fig. 1a
キメラマウス4N

May 21 ,2014 Letter Extended Data Fig. 1a reported by the media (NHK TV, Internet..)

4) Letter Extended Data Fig. 1a  It is suspected that t his image does not show 2N chimera, but rather 4N chimera, which is identical to that shown in Article Extended Data Fig. 7d (retraction note point 2) . ( This correction was made by the authors on May 10, 2014 and reported by the media on May 21, 2014.P.22,Report on STAP Cell Research Paper Investigation, Research Publication Investigative Committee, December 25, 2014

Jun

June 11, 2014 STAP cell had Trisomy8 (ES cell), by Nikkei Science ( by Dr.Endo Sep 21,2014)
trisomy8

June 12, 2014 Shukan-Bunshun created some suspicion.

June 12, 2014 Riken reform Committee propose dissolving Riken CDB.
Riken reform Committee

STAP cell laboratory by three monitoring camerapic: STAP cell laboratory for verification experiment by three monitoring camera.
Dr. Mikiko Shiomi said “We trust Dr.Takaho A Endo’s analysis because he is famous in this field. We think these result are reliable because not only Dr.Endo but one of Univ. of Tokyo’s group and one of Tokyo Inst. of Technology also gave same analysis.”
Teruo Kishi (Professor Emeritus, tokyo University) said "The debate is not settled until the person who assert existence of STAP cell give up or say "STAP cell do not exist", so it is necessary for us to try a scientific verification experiment. If your question is we think STAP cell not to exist, it would be substantially the same as our thoughts. "


――理研の遠藤高帆・上級研究員が発表した解析の結果の件。この結果によって、ES細胞の混入の可能性がかなり高まって、STAP細胞の存在自体を疑うレベルと委員会は評価しているのか? 塩見美喜子委員:評価している。遠藤高帆先生はこの領域では有名な先生で、解析は信頼のおけるものであるということ。それから遠藤先生だけではなくて、東工大のあるグループ、それから東大のあるグループも同じような解析をして、同じような結果が出ているということ。それから裏がとれているということで、信ぴょう性はかなり高いと考えている。理研改革委,2014年6月 弁護士ドットコムNEWS,2014年06月13日19時51分

June 16, 2014 STAP stem cell's gene type were not in Wakayama lab, CDB by Dr.Wakayama.
STAP-cell(FLS)Dr.Wakayama, RIKEN

June 25, 2014 Dr.Endo called Dr.Wakayama on the telephone to corrected cag primer of GFP with CAG and Acr. (see also July 22,2014) P.14, Aya Furuta, Masako Takuma, Nikkei Science Sep 2014.

July

July 1, 2014 Dr.Masayo Takahashi said she could not permit outlook on RIKEN's ethic on twitter.

July 2, 2014 Retraction

Nature On-line:“However, further analysis of the eight STAP-SC lines indicates that, while sharing the same 129×B6 F1 genetic background, they have a different GFP insertion site. ”
Nature (Paper):”However, further analysis of the eight STAP-SC lines indicates that, while sharing the same 129×B6 F1genetic background, they have a different GFP insertion site in chromosome 15.
Nature On-line:“The GFP transgene insertion site matches that of the mice and ES cells kept in the Wakayama laboratory. Thus, there are inexplicable discrepancies in genetic background and transgene insertion sites between the donor mice and the reported STAP-SCs.”

Nature(Paper):”The GFP transgene insertion site matches that of the mice and ES cells kept in the Wakayama laboratory (in chromosome 18). Thus, there are inexplicable discrepancies in genetic background and transgene insertion sites between the donor mice and the reported STAP-SCs. The origin of the cag-gfp insertion line in chromosome 15 was not from the mice at the Wakayama laboratory, as it was never maintained there.
Retraction: Stimulus-triggered fate conversion of somatic cells into pluripotency
6月16日に山梨大で行った会見内容の一部修正、およびNatureに掲載された撤回理由書の訂正について

July 4, 2014 Riken announced the plan of inspection experiment.
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July 4,2014 Dr. Noriko Osumi, the chief director of the molecular biology society of Japan lodged a complaint against RIKEN CDB and Dr.Obokata with Japanese society to stop the inspection experiment.

July 22, 2014 The analysis result (June 16,2014) was incorrect.
STAP-cell (FLS)
Dr.Wakayama, RIKEN

July, 2014 The directors of the molecular biology society of Japan lodged a complaint against RIKEN CDB and Dr.Obokata with Japanese society to stop the inspection experiment .

July 19, 2014 Dr.Sasai's last contribution for major medical journal Jikken-Igaku. Dr.Endo had begun to contribute some article about a next-generation sequencer in serial form to the journal.

July 23, 2014 Dr.Obokata followed by paparazzi NHK and injured.

July 25,2014 Science Council of Japan made a complaint against RIKEN to punish authors and analyze samples of STAP cell right away.
They said they cannot but suspect that the whole STAP cell research may be a fiction.

July 25,2014 A phial of propofol 50ml went missing in Kobe city medical center general hospital.

July 25,2014 山梨大学発生工学研究センター センター長 若山照彦博士指名

本件承認に伴い、山梨大学発生工学研究センター規程第4条第1項に基づき、学長が若山照彦教授(生命環境学部生命工学科)をセンター長に指名した。 第125回 教育研究評議会議事要録,山梨大学,平成26年7月25日

July 27, 2014 NHK reported on special TV program. Obokata and her lawyer are making a complaint against NHK about this program to Broadcasting Ethics & Program Improvement Organization. 「調査報告 STAP細胞 不正の深層 出演:藤原淳登科学文化部記者,若山照彦教授,遠藤高帆研究員,仲野徹大阪大学教授,篠原彰大阪大学教授,中山敬一九州大学教授,高濵洋介教授他」

July 2014 Dr.Sasai went missing.

Aug

Aug 2, 2014 Dr.Wakayama assumed a director of the center of Advanced biotechnology center, Yamanashi Univ.

Aug 5, 2014 Dr.Sasai passed away at Kobe city medical center general hospital

Aug 5,2014 A phial of propofol 50ml be found at Kobe city medical center general hospital.

Sep

Sep 21, 2014 STAP cell had Trisomy8 (ES cell) Dr.Takaho A Endo.
トリソミー

Dec

Dec 10,2014 A phial of propofol 50ml went missing in Kobe University Hospital.

Dec 11,2014

新エネルギー・産業技術総合開発機構(NEDO)は12月10日、東北大学、Clioらのグループと共同で、多能性幹細胞の一種であるMuse細胞からメラニン産生細胞を安定的に作り出す技術の開発に成功し、そこで得られたメラニン産生細胞を用いて3次元培養皮膚を作製する技術を確立したと発表した。…同技術はDSファーマバイオメディカルにライセンスされ、医薬品・化粧品の開発におけるスクリーニングや製品性能検証などに用いるキット「POCA ヒト3D HADA」として2015年1月15日より販売される。 NEDOなど、腫瘍性なく安全性の高いMuse細胞を用いた3次元培養皮膚を実用化,マイナビニュース2014年12月11日

Dec 19,2014 Dr.Aizawa and Dr.Niwa press conference. There are indeterminate something by ATP but it’s not phenomenon defined as Stimulus-Triggered Acquisition of Pluripotency cells.
Dr.Niwa's preprint doi: http://dx.doi.org/10.1101/027730 (Sep 28,2015).

Dec 26,2014 University of Tokyo press conference about Research Misconduct at the Research Laboratory of Former Professor Shigeaki Kato at the Institute of Molecular and Cellular Biosciences. He did 44 paper research misconduct . He is working for Radiation protection chief of Soma Central Hospital in Fukushima prefectur and present some reports about radiation pollution of the Accident at the Fukushima No.1 nuclear power plant.

Dec 26 2014,RIKEN press conference
核移植ES細胞
2005 Dr.Wakayama and Dr.Ohta doi: 10.1095/

The genetic background of the X chromosome in ES cell lines ntESG1 and ntESG2, which had the same Acr-GFP/CAG-GFP insertion, was B6. Since this is different from FLS3 and CTS1, those two ES cell lines were excluded from the comparison control P.5 2-3-1-1(b) 2) (1),Report on STAP Cell Research Paper Investigation,Research Publication Investigative Committee,Dec 25,2014
他方、同じAcr-GFP/CAG-GFPの挿入を持つES細胞ntESG1、およびntESG2のX染色体はC57BL/6で あることが判明したことから、調査対象のSTAP幹細胞FLS3、FI幹細胞CTS1と性染色体の構成が異なる ため、これらは比較解析の対照から除外された。P.5, 2-3-1-1(b) 2) (1), 研究論文に関する調査報告書, 平成26年12月25日

大田ES細胞
2005 Dr.Wakayama and Dr.Ohta doi: 10.1095/
C57BL/6-TgN(acro/act-EGFP)OsbC3-N01-FJ002; Background strain - C57BL/6Cr Slc glimmer body and tip of spermatozoa by exciting wavelength 480 nm

The SNPs on autosomes were similarly analyzed. Results indicated that STAP stem cell line FLS3, FI stem cell line CTS1, ES cell lines FES1 and FES2, and ES cell line 129/GFP ES in the stock of the Obokata lab had nearly the same genetic background as 129X1/SvJmsSlc x C57BL/6NCrSlc. P.5, Report on STAP Cell Research Paper Investigation ,Research Publication Investigative Committee, Dec 25,2014)
STAP幹細胞FLS3、FI幹細胞CTS1、およびES細胞FES1、FES2、ならびに小保方研ストックES細胞 129/GFPESは、ほぼ129x1/SvJmsSlcxC57BL/6NCrSlcの遺伝的背景を持つことが判明した。 P.5,研究論文に関する調査報告書,2014/12/25

Were STAP cells derived from ES cells?

2015

Jan 15, 2015 発売開始DSファーマバイオメディカルの「POCA® ヒト3D“HADA”」は、ヒトのケラチノサイト、ヒト幹細胞(Muse細胞)から分化させたメラノサイト、ファイブロブラストを Transwellプレートのインサートカップ内に播種した状態でお届けするヒト3D皮膚モデルのアッセイキットです。 ※本製品は株式会社Clioとのライセンス契約のもと作成しております。 細胞.jp

Jan 26, 2015 A former RIKEN researcher Dr. Tomohisa Ishikawa prosecuted her for theft about a Chinese student's ES cells that broadcasted by NHK on July 27,2014 with the popular magazine Friday.

Sep 22, 2015 "Failure to replicate the STAP cell phenomenon" Peter J. Park, George Q. Daley et al.

Sep 24, 2015 "STAP cells are derived from ES cells" Piero Carninci, Fumio Matsuzaki et al.

Sep 28, 2015 "Investigation of the cellular reprogramming phenomenon referred to as stimulus-triggered acquisition of pluripotency (STAP)" Hitoshi Niwa

Sep 28, 2015 "Transplantation of Unique Subpopulation of Fibroblasts, Muse Cells, Ameliorates Experimental Stroke Possibly Via Robust Neuronal Differentiation" Hiroki Uchida, Takahiro Morita, Kuniyasu Niizuma, Yoshihiro Kushida, Yasumasa Kuroda, Shohei Wakao, Hiroyuki Sakata, Yoshiya Matsuzaka, Hajime Mushiake, Teiji Tominaga, Cesario V. Borlongan, and Mari Dezawa. DOI: 10.1002/stem.2206

Oct 06, 2015

今回、東北大大学院医学系研究科の出澤真理教授と冨永悌二(ていじ)教授らが、ヒトの皮膚由来のミューズ細胞を脳梗塞のモデルラットに移植し、神経機能を回復させることに成功した。…ラットの頭に穴を開け、細い管で脳梗塞の場所に同細胞を送り込み移植したところ、細胞移植前には高い場所に設置した細い棒に乗せても棒につかまることしかできなかったラットが、移植から約3カ月後には棒の上を歩けるまでに回復した。  さらにラットの脳を詳しく調べると、同細胞が脳の組織に生着した後、自発的に神経に分化。脳から脊髄までの神経回路を再構築することが分かった。腫瘍ができないことも確認した。冨永教授は「脳梗塞の患者の骨髄からミューズ細胞を取り出し、脳にミューズ細胞を移植する臨床試験を2018年度から始めたい」としている。 東北大、ミューズ細胞を脳梗塞モデル動物に移植し運動能力が回復することを確認, 冨井哲雄, 日刊工業新聞2015年10月6日

クリエイティブ・コモンズ・ライセンス
Yuki Makuzuhara 作『Were STAP cells derived from ES cells?』はクリエイティブ・コモンズ 表示 4.0 国際 ライセンスで提供されています。
http://www.irasutoya.com/にある作品に基づいている。