title: Understanding the Molecular Basis of Heterogeneity in Induced Pluripotent Stem Cells.
abstract: Reprogramming of somatic cells to generate induced pluripotent stem cells (iPSCs) has considerable latency and generates epigenetically distinct partially and fully reprogrammed clones. To understand the molecular basis of reprogramming and to distinguish the partially reprogrammed iPSC clones (pre-iPSCs), we analyzed several of these clones for their molecular signatures. Using a combination of markers that are expressed at different stages of reprogramming, we found that the partially reprogrammed stable clones have significant morphological and molecular heterogeneity in their response to transition to the fully pluripotent state. The pre-iPSCs had significant levels of OCT4 expression but exhibited variable levels of mesenchymal-to-epithelial transition. These novel molecular signatures that we identified would help in using these cells to understand the molecular mechanisms in the late of stages of reprogramming. Although morphologically similar mouse iPSC clones showed significant heterogeneity, the human iPSC clones isolated initially on the basis of morphology were highly homogeneous with respect to the levels of pluripotency.
authors.affiliation: 1 Centre for Stem Cell Research, Christian Medical College , Vellore, Tamil Nadu, India .|2 Department of Haematology, Christian Medical College , Vellore, Tamil Nadu, India .
authors.forename: Kannan V
authors.initials: KV
authors.lastname: Manian
authors.affiliation: 1 Centre for Stem Cell Research, Christian Medical College , Vellore, Tamil Nadu, India .
authors.forename: Syed Mohammed Musheer
authors.initials: SM
authors.lastname: Aalam
authors.affiliation: 1 Centre for Stem Cell Research, Christian Medical College , Vellore, Tamil Nadu, India .|2 Department of Haematology, Christian Medical College , Vellore, Tamil Nadu, India .
authors.forename: Sumitha P
authors.initials: SP
authors.lastname: Bharathan
authors.affiliation: 1 Centre for Stem Cell Research, Christian Medical College , Vellore, Tamil Nadu, India .|2 Department of Haematology, Christian Medical College , Vellore, Tamil Nadu, India .
authors.forename: Alok
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: 1 Centre for Stem Cell Research, Christian Medical College , Vellore, Tamil Nadu, India .|2 Department of Haematology, Christian Medical College , Vellore, Tamil Nadu, India .
authors.forename: Shaji R
authors.initials: SR
authors.lastname: Velayudhan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050814:Octamer Transcription Factor-3 / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse