title: Neoblast specialization in regeneration of the planarian Schmidtea mediterranea.
abstract: Planarians can regenerate any missing body part in a process requiring dividing cells called neoblasts. Historically, neoblasts have largely been considered a homogeneous stem cell population. Most studies, however, analyzed neoblasts at the population rather than the single-cell level, leaving the degree of heterogeneity in this population unresolved. We combined RNA sequencing of neoblasts from wounded planarians with expression screening and identified 33 transcription factors transcribed in specific differentiated cells and in small fractions of neoblasts during regeneration. Many neoblast subsets expressing distinct tissue-associated transcription factors were present, suggesting candidate specification into many lineages. Consistent with this possibility, klf, pax3/7, and FoxA were required for the differentiation of cintillo-expressing sensory neurons, dopamine-β-hydroxylase-expressing neurons, and the pharynx, respectively. Together, these results suggest that specification of cell fate for most-to-all regenerative lineages occurs within neoblasts, with regenerative cells of blastemas being generated from a highly heterogeneous collection of lineage-specified neoblasts.
authors.affiliation: Howard Hughes Medical Institute, MIT Biology, and Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: M Lucila
authors.initials: ML
authors.lastname: Scimone
authors.affiliation: Howard Hughes Medical Institute, MIT Biology, and Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Kellie M
authors.initials: KM
authors.lastname: Kravarik
authors.affiliation: Howard Hughes Medical Institute, MIT Biology, and Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Sylvain W
authors.initials: SW
authors.lastname: Lapan
authors.affiliation: Howard Hughes Medical Institute, MIT Biology, and Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: reddien@wi.mit.edu.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Reddien
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D051536:Hepatocyte Nuclear Factors / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D051761:Paired Box Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010932:Planarians; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012038:Regeneration; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D051536:Hepatocyte Nuclear Factors; D051741:Kruppel-Like Transcription Factors; D051761:Paired Box Transcription Factors; D034741:RNA, Small Interfering; D014157:Transcription Factors