iHem cells – real or cell culture artifact?

by Alexey Bersenev on August 1, 2013 · 0 comments

in direct reprogramming

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The study, published in today’s issue of Cell Stem Cell, demonstrates a conversion of mouse fibroblasts into “hemogenic cells” via direct reprogramming approach. The authors used 4 defined transcription factors to induce “hemogenic program” in fibroblasts. The use of term “hemogenic cells” is the most appropriate in this case, because genetic profile of these cell resemble both – endothelial-like and hematopoietic-like cells (frequently referred as hemogenic endothelium), normally identified in embryonic aorta-gonad-mesonephros (AGM) region, placenta and fetal liver. Based entirely on genetic and phenotypic markers, we can not tell for sure what kind of cells have been isolated – hematopoietic stem cells or particular hematopoietic progenitors or endothelial progenitors or mix. Switching genetic programs and phenotypic plasticity is well known (artificially induced or accidental) cell culture artifact.

The commentary to this study calls it “iHem cells“. Commentary also says that iHem cells just joined iClub, which at this point included at least iNS, iN, iCM and iHep (induced- neural stem cell, neurons, cardiomyocytes and hepatocytes). Well, the commentary ignores Bhatia’s work, published in 2010, which demonstrated for the first time that iHem could be derived from human skin fibroblasts via direct reprogramming. So, iHem joined the iClub 3 years ago.

Reading Pereira’s study, we can appreciate how much work has been done to identify and tune up a “transcription factors cocktail”. The study design is elegant and smart. But while reading it, I was feeling like it’s really overloaded by redundant genetic analysis. The authors used all possible modern genetic analysis techniques (Fluidigm BioMark, metagene, gene set enrichment analysis, mRNA-seq…) to describe what they have got. Combination of all these methods allowed them to prove the hypothesis – “hemogenic program” can be successfully induced!

What missing in this study, in my opinion, is simple classical functional assays. Yes, I’m talking about transplantation assays to define hematopoietic cell function. The authors did only modified colony-forming unit assay, where they were able to identify myeloid-like cells. Without detection the function and in vivo studies we can not call iHem as hematopoietic stem cells or common myeloid progenitor. At this point we can call it only “iHem”. The future studies should address functionality and precise identity of iHem cells. What do you think?

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