TY - JOUR

T1 - Deterministic versus stochastic model of reprogramming

T2 - New evidence from cellular barcoding technique

AU - Yunusova, Anastasia M.

AU - Fishman, Veniamin S.

AU - Vasiliev, Gennady V.

AU - Battulin, Nariman R.

N1 - © 2017 The Authors.

PY - 2017/4

Y1 - 2017/4

N2 - Factor-mediated reprogramming of somatic cells towards pluripotency is a low-efficiency process during which only small subsets of cells are successfully reprogrammed. Previous analyses of the determinants of the reprogramming potential are based on average measurements across a large population of cells or on monitoring a relatively small number of single cells with live imaging. Here, we applied lentiviral genetic barcoding, a powerful tool enabling the identification of familiar relationships in thousands of cells. High-throughput sequencing of barcodes from successfully reprogrammed cells revealed a significant number of barcodes from related cells. We developed a computer model, according to which a probability of synchronous reprogramming of sister cells equals 10-30%. We conclude that the reprogramming success is pre-established in some particular cells and, being a heritable trait, can be maintained through cell division. Thus, reprogramming progresses in a deterministic manner, at least at the level of cell lineages.

AB - Factor-mediated reprogramming of somatic cells towards pluripotency is a low-efficiency process during which only small subsets of cells are successfully reprogrammed. Previous analyses of the determinants of the reprogramming potential are based on average measurements across a large population of cells or on monitoring a relatively small number of single cells with live imaging. Here, we applied lentiviral genetic barcoding, a powerful tool enabling the identification of familiar relationships in thousands of cells. High-throughput sequencing of barcodes from successfully reprogrammed cells revealed a significant number of barcodes from related cells. We developed a computer model, according to which a probability of synchronous reprogramming of sister cells equals 10-30%. We conclude that the reprogramming success is pre-established in some particular cells and, being a heritable trait, can be maintained through cell division. Thus, reprogramming progresses in a deterministic manner, at least at the level of cell lineages.

KW - Cell fate decisions

KW - Cellular barcoding

KW - Induced pluripotent stem cells

KW - Reprogramming to pluripotency

KW - Fibroblasts/cytology

KW - Cells, Cultured

KW - Transcription Factors/genetics

KW - Sequence Analysis, DNA

KW - Time-Lapse Imaging

KW - Cellular Reprogramming

KW - Induced Pluripotent Stem Cells/cytology

KW - Animals

KW - Doxycycline/pharmacology

KW - Models, Biological

KW - Recombinant Fusion Proteins/biosynthesis

KW - Genetic Vectors/genetics

KW - Embryo, Mammalian/cytology

KW - Green Fluorescent Proteins/genetics

KW - High-Throughput Nucleotide Sequencing

KW - Mice

KW - Lentivirus/genetics

KW - STATE

KW - cellular barcoding

KW - PLURIPOTENT STEM-CELLS

KW - GROWTH

KW - SOMATIC-CELLS

KW - MOUSE

KW - EMBRYONIC STEM

KW - cell fate decisions

KW - FIBROBLASTS

KW - GENERATION

KW - induced pluripotent stem cells

KW - DIFFERENTIATION

KW - reprogramming to pluripotency

KW - CLONAL ANALYSIS

UR - http://www.scopus.com/inward/record.url?scp=85019246875&partnerID=8YFLogxK

U2 - 10.1098/rsob.160311

DO - 10.1098/rsob.160311

M3 - Article

C2 - 28446707

AN - SCOPUS:85019246875

VL - 7

JO - Open Biology

JF - Open Biology

SN - 2046-2441

IS - 4

M1 - 160311

ER -