Tracking the progression of the human inner cell mass during embryonic stem cell derivation

• Published in: Nature biotechnology 2012-03, Vol.30 (3), p.278-282
• Main Authors: O'Leary, Thomas, Heindryckx, Björn, Lierman, Sylvie, van Bruggen, David, Goeman, Jelle J, Vandewoestyne, Mado, Deforce, Dieter, de Sousa Lopes, Susana M Chuva, De Sutter, Petra
• Format: Article
• Language: English
• Subjects: 631/136/532/2064/2117; 631/61; 631/61/490; 631/80; Agriculture; Animals; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Blastocyst Inner Cell Mass - cytology; Blastocyst Inner Cell Mass - metabolism; Cell differentiation; Cellular signal transduction; Developmental stages; Diverse techniques; Embryology; Embryonic growth stage; Embryonic stem cells; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Female; Fundamental and applied biological sciences. Psychology; Humans; Inactivation; letter; Life Sciences; Mice; Molecular and cellular biology; Molecular biology; Octamer Transcription Factor-3 - metabolism; Physiological aspects; Repressor Proteins - metabolism; RNA-Binding Proteins - metabolism; SOXB1 Transcription Factors - metabolism; Stem cells; X Chromosome Inactivation
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.2135

The events that lead from plated human blastocysts to embryonic stem cells are poorly understood. Close analysis reveals a transient intermediate state with a distinct molecular profile. The different pluripotent states of mouse embryonic stem cells (ESCs) in vitro have been shown to correspond to stages of mouse embryonic development 1 , 2 , 3 , 4 , 5 , 6 . For human cells, little is known about the events that precede the generation of ESCs or whether they correlate with in vivo developmental stages. Here we investigate the cellular and molecular changes that occur during the transition from the human inner cell mass (ICM) to ESCs in vitro . We demonstrate that human ESCs originate from a post-ICM intermediate (PICMI), a transient epiblast-like structure that has undergone X-inactivation in female cells and is both necessary and sufficient for ESC derivation. The PICMI is the result of progressive and defined ICM organization in vitro and has a distinct state of cell signaling. The PICMI can be cryopreserved without compromising ESC derivation capacity. As a closer progenitor of ESCs than the ICM, the PICMI provides insight into the pluripotent state of human stem cells.