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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development




 
Developmental biology - Cellular Identity

Who am I? How cells find their identity

How many ways are there to build a heart or a brain?...


The research group of Alex Schier, Director of the Biozentrum, University of Basel, Switzerland, has investigated more closely how a single embryonic cell develops into a heart, nerve or blood cell. For the first time, researchers have reconstructed the developmental trajectories of individual embryonic cells. Their results also suggest that cells can change their path during their maturation process. The results of the study with around 40,000 cells are published in Science.

The origin of every cell of our body is a single cell, the fertilized egg. On the way to become a specialized cell, whether blood, heart or nerve cells, its descendants follow a genetic program. This program determines the identity of a cell, its features and function.

The research team led by Alex Schier, Director of the Biozentrum, University of Basel, and currently still research group leader at Harvard University in Cambridge, has now developed a new method that enables the scientists for the first time to trace the entire history of the differentiation of individual cells. By combining the differentiation trajectories they have been able to construct a full developmental tree for embryogenesis. Furthermore, the team discovered that during differentiation, cells can leave their path and thus change their identity.

A widely branched tree for cell development

In their study, the team isolated around 40,000 cells and 25 different cell types that form in zebrafish over a period of nine hours. To investigate the maturation of these cells, they analyzed the RNA, a copy of the genetic material.
"The RNA tells us, which genes are active and determines the function and characteristics of a cell."

Alexander Schier PhD, Director Biozentrum, University of Basel, Switzerland and research group leader Harvard University, Cambridge, Massachusetts, USA.

In order to merge and compare the data, Schier's team developed a new software (URD). While previous studies in this field are based on the examination of a handful of genes, the new high-throughput single-cell RNA sequencing method enables the analysis of all active genes during cell development. With this new technology, the team has been able to reconstruct, for the first time, a widely branched tree that traces the development of each individual cell, starting with the fertilized egg cell. In addition, they mapped the cells to their spatial origin in the early embryo.

Finding cell identity is more flexible than expected

The results show that the genetic program that a cell follows on the way to maturity is by no means set in stone.
"It seems that the developmental path of a cell is more flexible than we previously expected."

Alexander Schier PhD

So far, it was assumed that developing cells follow a predetermined path, like marbles rolling down a hill until they stop at their predestined place. The study now suggests that signals from the environment can have such a strong influence on the cells, that they leave the initial trajectory and change their path, thus taking on a new identity.

Entire development as a cell lineage tree

In a next step, the research group will expand the cell lineage tree, investigate more cell types and follow the development of cells over a longer period of time.
"My aim is to merge the developmental trajectories and the lineage trees to one complete whole. If we can understand the logic behind cell differentiation, we may, one day, be able to answer the question: How many ways are there to build a heart or a brain?"

Alexander Schier PhD

Abstract
During embryogenesis, cells acquire distinct fates by transitioning through transcriptional states. To uncover these transcriptional trajectories during zebrafish embryogenesis, we sequenced 38,731 cells and developed URD, a simulated diffusion-based computational reconstruction method. URD identified the trajectories of 25 cell types through early somitogenesis, gene expression along them, and their spatial origin in the blastula. Analysis of Nodal signaling mutants revealed that their transcriptomes were canalized into a subset of wild-type transcriptional trajectories. Some wild-type developmental branchpoints contained cells expressing genes characteristic of multiple fates. These cells appeared to trans-specify from one fate to another. These findings reconstruct the transcriptional trajectories of a vertebrate embryo, highlight the concurrent canalization and plasticity of embryonic specification, and provide a framework to reconstruct complex developmental trees from single-cell transcriptomes.

Authors: Jeffrey A. Farrell1, Yiqun Wang1, Samantha J. Riensenfeld, Karthik Shekhar, Aviv Regev, Alexander F. Schier


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May 11, 2018   Fetal Timeline   Maternal Timeline   News   News Archive




During embryogenesis, cells acquire distinct fates. To uncover what these are, researchers sequenced 38,731 cells and developed a computational reconstruction method, URD, to identify cell trajectories of 25 types through to the early blastula stage. Analysis reflected cells with genes characteristic of multiple fates with cells that appear to jump from one fate to another. These findings highlight the plasticity of embryonic specification, providing a framework to reconstruct complex developmental trees. Image credit: Darryl Leja.


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