The basic leucine zipper transcriptionfactor C/EBP?, required for the in vivo transition of common myeloidprogenitor-to-GM progenitor. Myelomonocyte cell-type features are educed by theectopic expression of C/EBP? in primary bone marrow cells, lymphocytes or infibroblasts, where C/EBP? function along with PU.1, as deposition of H3K4me1 atenhancer elements of target genes demand this.Pax5 gets induced by the differentiation of CLPs to B-cell lineage rely on the TFsPU.1, E2A, and EBF1 which activates B-cell specificgenes meanwhile repressing genes associated with different lineages. B-lymphopoiesiscannot be accomplished by Pax5?/? pro-B-cells but can differentiate intoother hematopoietic cell types in response to explicit signalling cascades.When Pax5 is removed from mature B-cells it will result in dedifferentiation to uncommitted progenitor cell population,which will then undergo T-lymphopoiesis.
If the sequential expression of C/EBP?and GATA-2 in GM progenitors is altered then, the commitment will also change.Conversion of exocrine pancreas tissue toinsulin-secreting endocrine ?-cells invivo can be done by force expression of three bHLH TFs, Ngn3, Pdx1, andMafA, which were identified by Melton and co-workers. When hepatic progenitorcells are introduced with expression of only the endocrine progenitor-definingTF Ngn3, it generated physiologically responsive pancreatic endocrine cells.
But, in the case of mature hepatocytes in place of hepatic progenitor cells,only insulin expression in islet cells was induced. TFs Atoh1 and Prox1 werefound to be the one who modulate sensory hair cells and other supporting cellsdevelopment, which are from a common progenitor. Non-sensory cells of cochleawere converted to sensory hair cells due to ectopic expression of Atoh1. But,cellular degeneration occurred due to suppression of Gfi1 and Atoh1, which areimportant for sensory cells specification, by expression of Prox1. Besides inactivationof p19Arf, ectopic expression of GATA-4, Hnf1a, and Foxa3 in fibroblasts can give hepatocyte like cells.
In murineadult or embryonic fibroblasts can be induced as multiple hepatocyte, by the ectopicexpression of Hnf4? and one of the three foxA genes. Yamanakaand Melton, Wernig and co-workers shown that, the expression of three factors,Ascl1, Brn2 and Myt1l, in murine embryonic and postnatal fibroblasts induced transformation to neural (inducedneuronal/iN) cells, which are physiologically responsive and ableto constitute functional synapses. Neuronal differentiationof human ESCs can be possibly induced by those three factors but, supplementaryco-expression of NeuroD1 is needed for reprogramming of human fetal fibroblasts to functional iN cells. Lately Marro reprogrammedmurine hepatocytes into iN cells, to show neural conversion of a differentiated non-ectodermal cell type.
iN cells keeplimited epigenetic signature of their starting state and hepatic transcriptomeis repressed. To functional neural subtypes such as dopaminergic neurons and spinalmotor neurons human and mouse fibroblastsreprogramming can be done. Fibroblasts can be enticedto explicit neural lineage markers and demonstrate neuronal morphology entirelyby forced expression of microRNAs miR-9/9* and miR-124, which restrain theBaf53a subunit of the BAF chromatin-remodelling complex, with the expression ofanother two additional TFs. Because number of reprogrammed cells becamepost-mitotic within 24 hours of factor induction, reprogramming occurs inabsence of continued cell division. Generationof a variety of neuronal cells and cardiac muscle cells efficiently from ESCsor non-cardiac somatic is a big advancement in the field of translationalmedicine. It was evident for the first time of converting a non-cardiogenictissue to cardiac type, when a mice embryo was transfected with transcriptionalregulator, which is required for development of cardiac cell types.
Works of Srivastavaand co-workers has shown that induced cardiomyocytes can be generated byreprogramming of embryonic and adult fibroblasts using TFs GATA-4, Mef2C, andTbx5. This TF-mediatedreprogramming generates variety of cell types, which can be used in therapeutics,but requires more exploration. But the stability and comparative termination offunctional, transcriptional, and epigenetic remodelling, and the in vivo equivalenceof the generated cell types, remain unclear. By understanding the risks posedby incomplete reprogramming or cellular memory is an indicator of thetranslational application of induced cell types.
Reprogramming of Somatic Cells into Pluripotency c-Myc is not a core member of the ESCpluripotency network, but it is frequently included in the reprogramming factormixture, and expression c-Myc gene improve the efficiency of somatic cellreprogramming. Network controlled by this gene, basically comprise targets involvedin metabolic, cell cycle, and proliferative processes which is separated greatlyfrom core ESC pluripotency network. c-Myc target gene promoters are eminently enrichedfor the active histone modification H3K4me3 anddepleted of the repressive modification H3K27me3 in ESCs.