Title | Molecular recording of mammalian embryogenesis. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Chan, MM, Smith, ZD, Grosswendt, S, Kretzmer, H, Norman, TM, Adamson, B, Jost, M, Quinn, JJ, Yang, D, Jones, MG, Khodaverdian, A, Yosef, N, Meissner, A, Weissman, JS |
Journal | Nature |
Volume | 570 |
Issue | 7759 |
Pagination | 77-82 |
Date Published | 2019 Jun |
ISSN | 1476-4687 |
Keywords | Animals, Cell Differentiation, Cell Lineage, Embryo, Mammalian, Embryonic Development, Embryonic Stem Cells, Endoderm, Female, Fertilization, Gastrulation, Gene Expression Regulation, Developmental, Male, Mice, Organ Specificity, Phenotype, Sequence Analysis, RNA, Single-Cell Analysis |
Abstract | <p>Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes.</p> |
DOI | 10.1038/s41586-019-1184-5 |
Alternate Journal | Nature |
PubMed ID | 31086336 |
PubMed Central ID | PMC7229772 |
Grant List | T32 HG000047 / HG / NHGRI NIH HHS / United States F32 GM116331 / GM / NIGMS NIH HHS / United States RM1 HG009490 / HG / NHGRI NIH HHS / United States R01 DA036858 / DA / NIDA NIH HHS / United States R01 HD078679 / HD / NICHD NIH HHS / United States P50 HG006193 / HG / NHGRI NIH HHS / United States F32 GM125247 / GM / NIGMS NIH HHS / United States |